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Sample records for genetic predisposition environmental

  1. Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition.

    Science.gov (United States)

    Husted, Janice A; Ahmed, Rashid; Chow, Eva W C; Brzustowicz, Linda M; Bassett, Anne S

    2012-05-01

    There are few studies of environmental factors in familial forms of schizophrenia. We investigated whether childhood adversity or environmental factors were associated with schizophrenia in a familial sample where schizophrenia is associated with the NOSA1P gene. We found that a cumulative adversity index including childhood illness, family instability and cannabis use was significantly associated with narrow schizophrenia, independent of NOSA1P risk genotype, previously measured childhood trauma, covariates and familial clustering (adjusted odds ratio (95% confidence interval)=1.55 (1.01, 2.38)). The results provide further support that early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Dietary management and genetic predisposition

    DEFF Research Database (Denmark)

    Jensen, Hanne Holbæk; Larsen, Lesli Hingstrup

    2013-01-01

    variation, and epigenetics might identify additional genetic contributions to obesity, and the use of omics data with integration of nutrigenetics and nutrigenomics will identify genetic subgroups who will benefit from specific dietary advice to optimize health and prevent disease. Keywords: Diet . Mutation...... epidemically worldwide, the investigation of genetic predisposition might help to prevent and treat obesity. Predisposition to obesity includes syndromes, such as Prader-Willi Syndrome (PWS), severe early-onset obesity, such as mutations in the melanocortin 4 receptor (MC4R), and common forms of obesity......, such as genetic variation in the fat mass and obesity associated gene (FTO). Several studies have explored gene-diet interactions in obesity, weight loss, and regain, but there is a lack of consistency in the identified interactions. This inconsistency is most probably due to a low-moderate effect size...

  3. Genetic predisposition and implications for radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, Christian [University Clinics, Essen, Essen (Germany)

    2000-05-01

    Treatments of cancer patients with ionizing radiation have shown in some cases severe acute radiation effects after radiation doses which are very well tolerated by most patients. Skin fibroblasts of these patients studied after in vitro irradiation also showed a high radiosensitivity frequently. It was found that these effects are based on genetic predisposition which was usually inherited from their parents. During recent years quite a number of these syndromes have been described in humans and often the responsible genes have been characterized: Ataxia telangiectasia, Bloom's syndrome, Fanconi anemia, Li Fraumeni syndrome, Nevoid basal cell carcinoma syndrome, Neurofibromatosis, Nijmegen breakage syndrome, Retinoblastoma. In most cases it was found that the regulation processes of DNA repair processes and of the cell cycle for cell proliferation are disturbed. Frequently these processes cannot be separated from each other. Quite a number of these syndromes also show genomic instability which can also be induced by radiation exposures. These Phenomena have mainly been studied by determining the rate of chromosomal aberrations many cell generations after the exposure took place. Genomic instability apparently plays an important role for the development of stochastic late effects for which multistep events are necessary. This is especially for carcinogenesis the case. In mice it has been shown that radiation-induced genomic instability can be transmitted to the next mouse generation. In mouse models and also with radiotherapy patients it has been shown that genetic predisposition not only increases radiosensitivity with respect to cell survival and chromosomal damage but also to carcinogenesis. This has been observed cf. with p53-knock out mice and with children after radiotherapy cf. treatment of retinoblastoma. In the children with a genetic predisposition for retinoblastoma secondary tumours occurred to a much higher rate than in those children with

  4. Genetic predisposition and implications for radioprotection

    International Nuclear Information System (INIS)

    Streffer, Christian

    2000-01-01

    Treatments of cancer patients with ionizing radiation have shown in some cases severe acute radiation effects after radiation doses which are very well tolerated by most patients. Skin fibroblasts of these patients studied after in vitro irradiation also showed a high radiosensitivity frequently. It was found that these effects are based on genetic predisposition which was usually inherited from their parents. During recent years quite a number of these syndromes have been described in humans and often the responsible genes have been characterized: Ataxia telangiectasia, Bloom's syndrome, Fanconi anemia, Li Fraumeni syndrome, Nevoid basal cell carcinoma syndrome, Neurofibromatosis, Nijmegen breakage syndrome, Retinoblastoma. In most cases it was found that the regulation processes of DNA repair processes and of the cell cycle for cell proliferation are disturbed. Frequently these processes cannot be separated from each other. Quite a number of these syndromes also show genomic instability which can also be induced by radiation exposures. These Phenomena have mainly been studied by determining the rate of chromosomal aberrations many cell generations after the exposure took place. Genomic instability apparently plays an important role for the development of stochastic late effects for which multistep events are necessary. This is especially for carcinogenesis the case. In mice it has been shown that radiation-induced genomic instability can be transmitted to the next mouse generation. In mouse models and also with radiotherapy patients it has been shown that genetic predisposition not only increases radiosensitivity with respect to cell survival and chromosomal damage but also to carcinogenesis. This has been observed cf. with p53-knock out mice and with children after radiotherapy cf. treatment of retinoblastoma. In the children with a genetic predisposition for retinoblastoma secondary tumours occurred to a much higher rate than in those children with

  5. Genetic predisposition toward suicidal ideation in patients with acute coronary syndrome.

    Science.gov (United States)

    Kang, Hee-Ju; Bae, Kyung-Yeol; Kim, Sung-Wan; Shin, Il-Seon; Hong, Young Joon; Ahn, Youngkeun; Jeong, Myung Ho; Yoon, Jin-Sang; Kim, Jae-Min

    2017-11-07

    The genetic predisposition toward suicidal ideation has been explored to identify subgroups at high risk and to prevent suicide. Acute coronary syndrome (ACS) is associated with an increased risk of suicide, but few studies have explored the genetic predisposition toward suicide in ACS populations. Therefore, this longitudinal study explored the genetic predisposition toward suicidal ideation in ACS patients. In total, of 969 patients within 2 weeks after ACS, 711 were followed at 1 year after ACS. Suicidal ideation was evaluated with the relevant items on the Montgomery-Åsberg Depression Rating Scale. Ten genetic polymorphisms associated with serotonergic systems, neurotrophic factors, carbon metabolism, and inflammatory cytokines were examined. Associations between genetic polymorphisms and suicidal ideation within 2 weeks and 1 year of ACS were investigated using logistic regression models. The 5-HTTLPR s allele was significantly associated with suicidal ideation within 2 weeks of ACS after adjusting for covariates and after the Bonferroni correction. TNF-α -308 G/A , IL-1β -511 C/T , and IL-1β + 3953C/T were significantly associated with suicidal ideation within 2 weeks after ACS, but these associations did not reach significance after the Bonferroni correction in unadjusted analyses and after adjusting for covariance. However, no significant association between genetic polymorphisms and suicidal ideation was found at 1 year. Genetic predisposition, 5-HTTLPR s allele in particular, may confer susceptibility to suicidal ideation in ACS patients during the acute phase of ACS.

  6. Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.

    Science.gov (United States)

    Spracklen, Cassandra N; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2015-07-01

    Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Genetic predisposition increases the tic severity, rate of comorbidities, and psychosocial and educational difficulties in children with Tourette syndrome.

    Science.gov (United States)

    Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

    2015-03-01

    This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic predisposition. Professionals need to be aware of genetic predisposition to Tourette syndrome, as children with Tourette syndrome and genetic predisposition have more severe symptoms than those children with Tourette syndrome who are without genetic predisposition. © The Author(s) 2014.

  8. Integrated screening concept in women with genetic predisposition for breast cancer

    International Nuclear Information System (INIS)

    Bick, U.

    1997-01-01

    Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [de

  9. Genetic and environmental interactions

    International Nuclear Information System (INIS)

    Strong, L.C.

    1977-01-01

    Cancer may result from a multistage process occurring over a long period of time. Presumably, initial and progressive stages of carcinogenesis may be modified by both genetic and environmental factors. Theoretically, genetic factors may alter susceptibility to the carcinogenic effects of an environmental agent at the initial exposure due to variation in metabolism of the carcinogen or variation in specific target cell response to the active carcinogen, or during the latent phase due to numerous factors that might increase the probability of tumor expression, including growth-promoting factors or immunodeficiency states. Observed genetic and environmental interactions in carcinogenesis include an association between genetically determined inducibility of aryl hydrocarbon hydroxylase and smoking-related cancers, familial susceptibility to certain environmental carcinogens, an association between hereditary disorders of mutagenesis and carcinogenesis, and enhancement of tissue-specific, dominantly inherited tumor predisposition by radiation. Multiple primary tumors occur frequently in genetically predisposed individuals. Specific markers for susceptibility must be sought in order that high-risk individuals be identified and appropriate measures taken for early cancer detection or prevention. Study of the nature of the genetically determined susceptibility and interactions with environmental agents may be revealing in the understanding of carcinogenesis in general

  10. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

    Science.gov (United States)

    Babushok, Daria V; Bessler, Monica

    2015-03-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population.

    Science.gov (United States)

    Shaukat, Uzma; Ismail, Muhammad; Mehmood, Nasir

    2013-01-01

    Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

  12. Genetic and familial predisposition to rotator cuff disease: a systematic review.

    Science.gov (United States)

    Dabija, Dominique I; Gao, Chan; Edwards, Todd L; Kuhn, John E; Jain, Nitin B

    2017-06-01

    Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and is likely to extend beyond repetitive microtrauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. A literature search of PubMed and Embase databases identified 251 citations. After review of the titles, abstracts, and full articles, 7 met our inclusion and exclusion criteria. Four studies assessed familial predisposition to rotator cuff disease. One of these demonstrated that siblings of an individual with a rotator cuff tear were more likely to develop a full-thickness tear and more likely to be symptomatic. A 5-year follow-up showed that the relative risks were increased for the siblings to have a full-thickness tear, for a tear to progress in size, and for being symptomatic. Another study demonstrated that a significantly higher number of individuals with tears had family members with a history of tears or surgery than those without tears did. The other 3 studies investigated whether a genetic predisposition to rotator cuff disease exists and found significant association of haplotypes in DEFB1, FGFR1, FGF3, ESRRB, and FGF10 and 2 single-nucleotide polymorphisms within SAP30BP and SASH1. Prior studies provide preliminary evidence for genetic and familial predisposition to rotator cuff disease. However, there is a lack of large genome-wide studies that can provide more definitive information and guide early detection of individuals at risk, prophylactic rehabilitation, and potential gene therapies and regenerative medicine interventions. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  13. Maxillary canine displacement and genetically determined predisposition to disturbed development of the dentition.

    Science.gov (United States)

    Stahl, Franka; Grabowski, Rosemarie

    2003-05-01

    The relationship between maxillary canine displacement and the simultaneous occurrence of "genetically determined predisposition to disturbed development of the dentition" as defined by Hoffmeister was investigated in 675 patients. Panoramic radiographs taken of each patient during the first and the second mixed dentition periods were evaluated. Canine inclination and the distance between the tip of the canine and a line connecting the cusps of the molars were computed in five different age groups according to Dausch-Neumann. Statistical analysis revealed 34 patients with "potential canine displacement", who exhibited further symptoms of "genetically determined predisposition to disturbed development of the dentition" significantly more frequently than the total group. The symptoms concerned were agenesia, displaced tooth buds, rotated or tilted incisors, aplasia and microdontia of lateral incisors. Careful follow-ups in patients with a predisposition to disturbed dental development enables risks to be anticipated and canine displacement to be detected at an early stage.

  14. Genetic predisposition to kidney cancer.

    Science.gov (United States)

    Schmidt, Laura S; Linehan, W Marston

    2016-10-01

    Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes. Published by Elsevier Inc.

  15. Genetic Predisposition Increases the Tic Severity, Rate of Comorbidities, and Psychosocial and Educational Difficulties in Children With Tourette Syndrome

    DEFF Research Database (Denmark)

    Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

    2015-01-01

    This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition...... to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related...... to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic...

  16. Pediatric Predispositional Genetic Risk Communication: Potential Utility for Prevention and Control of Melanoma Risk as an Exemplar.

    Science.gov (United States)

    Wu, Yelena P; Mays, Darren; Kohlmann, Wendy; Tercyak, Kenneth P

    2017-10-01

    Predispositional genetic testing among minor children is intensely debated due to the potential benefits and harms of providing this type of genetic information to children and their families. Existing guidelines on pediatric genetic testing state that predispositional testing could be appropriate for minors if preventive services exist that mitigate children's risk for or severity of the health condition in question. We use the example of hereditary melanoma to illustrate the rationale for and potential application of genetic risk communication for an adult-onset cancer to a pediatric population where childhood behaviors may reduce risk of disease later in life. We draw from the adult melanoma genetic risk communication and pediatric health behavior change literatures to suggest ways in which genetic test reporting and complementary education could be delivered to children who carry a hereditary risk for melanoma and their families in order to foster children's engagement in melanoma preventive behaviors. Genetic discoveries will continue to yield new opportunities to provide predispositional genetic risk information to unaffected individuals, including children, and could be delivered within programs that provide personalized and translational approaches to cancer prevention.

  17. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    NARCIS (Netherlands)

    Rueda, B.; Broen, J.; Simeon, C.; Hesselstrand, R.; Diaz, B.; Suarez, H.; Ortego-Centeno, N.; Riemekasten, G.; Fonollosa, V.; Vonk, M.C.; Hoogen, F.H.J. van den; Sanchez-Roman, J.; Aguirre-Zamorano, M.A.; Garcia-Portales, R.; Pros, A.; Camps, M.T.; Gonzalez-Gay, M.A.; Coenen, M.J.H.; Airo, P.; Beretta, L.; Scorza, R.; Laar, J. van; Gonzalez-Escribano, M.F.; Nelson, J.L.; Radstake, T.R.D.J.; Martin, J.

    2009-01-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy

  18. Education modifies genetic and environmental influences on BMI

    DEFF Research Database (Denmark)

    Johnson, Wendy; Kyvik, Kirsten Ohm; Skytthe, Axel

    2011-01-01

    environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were -.13 in women, -.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due...... to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI......Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight...

  19. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

    Science.gov (United States)

    Waszak, Sebastian M; Northcott, Paul A; Buchhalter, Ivo; Robinson, Giles W; Sutter, Christian; Groebner, Susanne; Grund, Kerstin B; Brugières, Laurence; Jones, David T W; Pajtler, Kristian W; Morrissy, A Sorana; Kool, Marcel; Sturm, Dominik; Chavez, Lukas; Ernst, Aurelie; Brabetz, Sebastian; Hain, Michael; Zichner, Thomas; Segura-Wang, Maia; Weischenfeldt, Joachim; Rausch, Tobias; Mardin, Balca R; Zhou, Xin; Baciu, Cristina; Lawerenz, Christian; Chan, Jennifer A; Varlet, Pascale; Guerrini-Rousseau, Lea; Fults, Daniel W; Grajkowska, Wiesława; Hauser, Peter; Jabado, Nada; Ra, Young-Shin; Zitterbart, Karel; Shringarpure, Suyash S; De La Vega, Francisco M; Bustamante, Carlos D; Ng, Ho-Keung; Perry, Arie; MacDonald, Tobey J; Hernáiz Driever, Pablo; Bendel, Anne E; Bowers, Daniel C; McCowage, Geoffrey; Chintagumpala, Murali M; Cohn, Richard; Hassall, Timothy; Fleischhack, Gudrun; Eggen, Tone; Wesenberg, Finn; Feychting, Maria; Lannering, Birgitta; Schüz, Joachim; Johansen, Christoffer; Andersen, Tina V; Röösli, Martin; Kuehni, Claudia E; Grotzer, Michael; Kjaerheim, Kristina; Monoranu, Camelia M; Archer, Tenley C; Duke, Elizabeth; Pomeroy, Scott L; Shelagh, Redmond; Frank, Stephan; Sumerauer, David; Scheurlen, Wolfram; Ryzhova, Marina V; Milde, Till; Kratz, Christian P; Samuel, David; Zhang, Jinghui; Solomon, David A; Marra, Marco; Eils, Roland; Bartram, Claus R; von Hoff, Katja; Rutkowski, Stefan; Ramaswamy, Vijay; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Malkin, David; Gajjar, Amar; Korbel, Jan O; Pfister, Stefan M

    2018-06-01

    Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MB WNT ), SHH (MB SHH ), group 3 (MB Group3 ), and group 4 (MB Group4 ). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these against 53 105

  20. Interaction between genetic predisposition to obesity and dietary calcium in relation to subsequent change in body weight and waist circumference

    DEFF Research Database (Denmark)

    Larsen, Sofus C; Angquist, Lars; Ahluwalia, Tarun Veer Singh

    2014-01-01

    Studies indicate an effect of dietary calcium on change in body weight (BW) and waist circumference (WC), but the results are inconsistent. Furthermore, a relation could depend on genetic predisposition to obesity.......Studies indicate an effect of dietary calcium on change in body weight (BW) and waist circumference (WC), but the results are inconsistent. Furthermore, a relation could depend on genetic predisposition to obesity....

  1. Linking energy behaviour, attitude and habits with environmental predisposition and knowledge

    Science.gov (United States)

    Pothitou, Mary; Varga, Liz; Kolios, Athanasios J.; Gu, Sai

    2017-04-01

    The purpose of this paper is to present and discuss the findings of an empirical study that compares individuals' environmental predisposition and knowledge with their energy behaviour, attitude and habits. Additionally, the study attempts to correlate education level and household income with the above variables. The statistical analysis reveals significant correlations between environmental predisposition and knowledge and elements of individuals' energy attitudes, habits and behaviour. An unanticipated outcome from the principal component analysis was that household income, and to a lesser extent gender, is associated with energy-saving habits and behaviours. On further investigation, household income was found to be correlated with knowledge of greenhouse gas emissions and the number of laptops and electric showers owned per household. The study sample comprises 68 employees of an educational institution, which was selected as the first phase of research aiming to compare energy-saving behaviour at home and in the workplace.

  2. Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.

    Science.gov (United States)

    Walker, Celia G; Solis-Trapala, Ivonne; Holzapfel, Christina; Ambrosini, Gina L; Fuller, Nicholas R; Loos, Ruth J F; Hauner, Hans; Caterson, Ian D; Jebb, Susan A

    2015-01-01

    The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention.

  3. Association of Genetic Predisposition With Solitary Schwannoma or Meningioma in Children and Young Adults.

    Science.gov (United States)

    Pathmanaban, Omar N; Sadler, Katherine V; Kamaly-Asl, Ian D; King, Andrew T; Rutherford, Scott A; Hammerbeck-Ward, Charlotte; McCabe, Martin G; Kilday, John-Paul; Beetz, Christian; Poplawski, Nicola K; Evans, D Gareth; Smith, Miriam J

    2017-09-01

    predisposition gene. Twenty-five of 63 patients (40%) had a constitutional NF2 mutation, and 9 (14%) had a constitutional SMARCE1 mutation. In the cohort of those who developed a solitary schwannoma before age 25 years, 44 of 153 patients (29%) had an identifiable genetic predisposition. Twenty-four patients (55%) with a spinal schwannoma had a constitutional mutation, while only 20 (18%) with a cranial schwannoma had a constitutional predisposition (P young people with an apparently sporadic solitary meningioma or schwannoma had a causative predisposition mutation. This finding has important clinical implications because of the risk of additional tumors and the possibility of familial disease. Young patients presenting with a solitary meningioma or schwannoma should be referred for genetic testing.

  4. The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity

    Directory of Open Access Journals (Sweden)

    Louise Aas Nielsen

    2015-10-01

    Full Text Available The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events, and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring.

  5. The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity

    Science.gov (United States)

    Nielsen, Louise Aas; Nielsen, Tenna Ruest Haarmark; Holm, Jens-Christian

    2015-01-01

    The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring. PMID:26465142

  6. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    Science.gov (United States)

    Rueda, B; Broen, J; Simeon, C; Hesselstrand, R; Diaz, B; Suárez, H; Ortego-Centeno, N; Riemekasten, G; Fonollosa, V; Vonk, M C; van den Hoogen, F H J; Sanchez-Román, J; Aguirre-Zamorano, M A; García-Portales, R; Pros, A; Camps, M T; Gonzalez-Gay, M A; Coenen, M J H; Airo, P; Beretta, L; Scorza, R; van Laar, J; Gonzalez-Escribano, M F; Nelson, J L; Radstake, T R D J; Martin, J

    2009-06-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.

  7. Genetic predispositions and parental bonding interact to shape adults’ physiological responses to social distress

    Science.gov (United States)

    Esposito, Gianluca; Truzzi, Anna; Setoh, Peipei; Putnick, Diane L.; Shinohara, Kazuyuki; Bornstein, Marc H.

    2018-01-01

    Parental bonding and oxytocin receptor (OXTR) gene genotype each influences social abilities in adulthood. Here, we hypothesized an interaction between the two – environmental experience (parental bonding history) and genetic factors (OXTR gene genotype) – in shaping adults’ social sensitivity (physiological response to distress). We assessed heart rate and peripheral temperature (tip of the nose) in 42 male adults during presentation of distress vocalizations (distress cries belonging to female human infants and adults as well as bonobo). The two physiological responses index, respectively, state of arousal and readiness to action. Participants’ parental bonding in childhood was assessed through the self-report Parental Bonding Instrument. To assess participants’ genetic predispositions, buccal mucosa cell samples were collected, and region rs2254298 of the oxytocin receptor gene was analyzed: previous OXTR gene findings point to associations between the G allele and better sociality (protective factor) and the A allele and poorer sociality (risk factor). We found a gene * environment interaction for susceptibility to social distress: Participants with a genetic risk factor (A carriers) with a history of high paternal overprotection showed higher heart rate increase than those without this risk factor (G/G genotype) to social distress. Also, a significant effect of the interaction between paternal care and genotype on nose temperature changes was found. This susceptibility appears to represent an indirect pathway through which genes and experiences interact to shape mature social sensitivity in males. PMID:27343933

  8. Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study.

    Directory of Open Access Journals (Sweden)

    Shengxu Li

    2010-08-01

    Full Text Available We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study.We genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y from the European Prospective Investigation of Cancer (EPIC-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error [SE] 0.012 kg/m(2 (p = 6.73 x 10(-37 increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall. This association was significantly (p(interaction = 0.005 more pronounced in inactive people (0.205 [SE 0.024] kg/m(2 [p = 3.62 x 10(-18; 592 g in weight] than in active people (0.131 [SE 0.014] kg/m(2 [p = 7.97 x 10(-21; 379 g in weight]. Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26 in the whole population, but significantly (p(interaction = 0.015 more in inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(-16] than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1

  9. Television watching, leisure time physical activity, and the genetic predisposition in relation to body mass index in women and men.

    Science.gov (United States)

    Qi, Qibin; Li, Yanping; Chomistek, Andrea K; Kang, Jae H; Curhan, Gary C; Pasquale, Louis R; Willett, Walter C; Rimm, Eric B; Hu, Frank B; Qi, Lu

    2012-10-09

    Previous studies on gene-lifestyle interaction and obesity have focused mostly on the FTO gene and physical activity, whereas little attention has been paid to sedentary behavior as indicated by television (TV) watching. We analyzed interactions between TV watching, leisure time physical activity, and genetic predisposition in relation to body mass index (BMI) in 7740 women and 4564 men from 2 prospective cohorts: The Nurses' Health Study and the Health Professionals Follow-up Study. Data on physical activity and TV watching were collected 2 years before assessment of BMI. A weighted genetic risk score was calculated on the basis of 32 established BMI-associated variants. In both women and men, the genetic associations with BMI strengthened with increased hours of TV watching. An increment of 10 points in the weighted genetic risk score was associated with 0.8 (SE, 0.4), 0.8 (SE, 0.2), 1.4 (SE, 0.2), 1.5 (SE, 0.2), and 3.4 (SE, 1.0) kg/m(2) higher BMI across the 5 categories of TV watching (0-1, 2-5, 6-20, 21-40, and >40 h/wk; P for interaction=0.001). In contrast, the genetic association with BMI weakened with increased levels of physical activity. An increment of 10 points in the weighted genetic risk score was associated with 1.5 (SE, 0.2), 1.3 (SE, 0.2), 1.2 (SE, 0.2), 1.2 (SE, 0.2), and 0.8 (SE, 0.2) kg/m(2) higher BMI across the quintiles of physical activity. The interactions of TV watching and physical activity with genetic predisposition in relation to BMI were independent of each other. A sedentary lifestyle, indicated by prolonged TV watching, may accentuate the predisposition to elevated adiposity, whereas greater leisure time physical activity may attenuate the genetic association.

  10. Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Juan Wu

    2014-01-01

    Full Text Available Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP, the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease.

  11. Lung cancer, genetic predisposition and smoking

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob; Korhonen, Tellervo; Holst, Klaus

    2017-01-01

    Background: We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status. Methods: Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time...

  12. Genetic predisposition for radiation-induced bone tumors

    International Nuclear Information System (INIS)

    Rosemann, M.; Luz, A.; Kuosaite, V.; Favor, J.; Atkinson, M.J.; Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen, Neuherberg

    1999-01-01

    The interaction between environmental factors and genetic determinants is crucial for the development of malignant tumours. However, the hereditary factors involved in the development of cancer that have been recognised so far are only responsible for at the most ten percent of tumours. It is still a matter of dispute whether the remaining 90 percent - so-called sporadic tumours - really have a cause that is free of genetic influence. There are good reasons for believing that there are a large number of genes in the human genome that confer resistance or susceptibility for tumorigenesis, and thus lead to natural genetic variability. (orig.) [de

  13. Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats.

    Science.gov (United States)

    Vogel, Heike; Kraemer, Maria; Rabasa, Cristina; Askevik, Kaisa; Adan, Roger A H; Dickson, Suzanne L

    2017-06-15

    Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition.

    LENUS (Irish Health Repository)

    Baeyens, A

    2002-12-02

    The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%).

  15. Significance of genetic predisposition and genomic instability for individual sensitivity to radiation. Implications for radiation protection

    International Nuclear Information System (INIS)

    Heller, H.

    2001-01-01

    At its closed-door meeting on 20/21 January 2000 the Radiation Protection Committee dedicated much of its attention to the significance of genetic predisposition and genetic instability for individual radiation sensitivity and to the implication of this for radiation protection. The statements and contributions to the closing plenary discussion touched on many aspects of ethics, personal rights, occupational medicine and insurance issues relating to this subject, all of which extend far beyond the purely technical issues of radiation protection. The present volume contains the lecture manuscripts of the meeting as well as a summarising assessment by the Radiation Protection Committee [de

  16. Testing positive for a genetic predisposition to depression magnifies retrospective memory for depressive symptoms.

    Science.gov (United States)

    Lebowitz, Matthew S; Ahn, Woo-Kyoung

    2017-11-01

    Depression, like other mental disorders and health conditions generally, is increasingly construed as genetically based. This research sought to determine whether merely telling people that they have a genetic predisposition to depression can cause them to retroactively remember having experienced it. U.S. adults (men and women) were recruited online to participate (Experiment 1: N = 288; Experiment 2: N = 599). After conducting a test disguised as genetic screening, we randomly assigned some participants to be told that they carried elevated genetic susceptibility to depression, whereas others were told that they did not carry this genetic liability or were told that they carried elevated susceptibility to a different disorder. Participants then rated their experience of depressive symptoms over the prior 2 weeks on a modified version of the Beck Depression Inventory-II. Participants who were told that their genes predisposed them to depression generally reported higher levels of depressive symptomatology over the previous 2 weeks, compared to those who did not receive this feedback. Given the central role of self-report in psychiatric diagnosis, these findings highlight potentially harmful consequences of personalized genetic testing in mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Genetic predisposition to ductal carcinoma in situ of the breast

    DEFF Research Database (Denmark)

    Petridis, Christos; Brook, Mark N; Shah, Vandna

    2016-01-01

    BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci...... %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen......, or whether there are differences in the strength of association for shared loci. METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. RESULTS: Most (67...

  18. Gene-Specific-Candidate-Driven Study to decipher Genetic Predisposition to Rotavirus Infection

    Directory of Open Access Journals (Sweden)

    Kshitija Rane-Yadav

    2017-10-01

    Full Text Available Recent report of WHO shows 113000 children in India succumb to death due to Rotavirus diarrhea. Lack of knowledge about pathogenesis of virus has led to lack of therapy for severely infected patients. Previous studies have found that, animal rotavirus requires sialyl glycan moieties on cell surface for pathogenesis. Present study states that human rotaviruses also follows same path and this specificity of virus leads to host genetic predisposition for the infection as well as the disease. Two hundred children less than 5 years of age clinically suspected of viral diarrhea were screened for rotavirus infection. EDTA blood was processed for analyzing DNA sequences of various fucosyltransferase genes. Lewis antigens which are secretory form of ABO Histo Blood Group Antigens were correlated with the genotype of patient. Genetics of HBGA secretion, particularly, basis of Leb expression manifested by fucosyltransferase-2 enzyme was studied in healthy individuals and was compared in cases of rotavirus positive and negative diarrhea. Positive clinical isolates with various genotypes were purified from stool samples and gene for VP4 - surface spike protein was sequenced. Using Bioinformatics interphase, three dimensional protein structures were modeled and their functional domains were analyzed. All these modeled proteins were docked with Leb HBGA (Lewis-b Histo Blood Group Antigens using molecular docking software. In present study, to investigate possible association of the rotavirus with host genome, we screened highly suspected genes involved in expression of glycoproteins on enterocytes. This study performed for prevalent Indian strains of rotaviruses provides possible evidence that, VP8 domain of VP4 spike protein utilizes Leb surface antigen for attachment and entry to enterocytes in the intestine. The FUT2 and FUT3 gene has been found to show significant association with the rotavirus infection hence can serve as a biomarker for genetic

  19. Population-genetic approach to standardization of radiation and non-radiation factors

    International Nuclear Information System (INIS)

    Telnov, I.

    2006-01-01

    Numerous studies demonstrate the importance of genetic predisposition in the development of wide range of pathologies and unfavorable effects caused by different factors. This prompts to account for genetic factors in the risk assessment of unfavorable effects. Current approaches used to solve this problem are far from perfect. On the one hand, recommendations on occupational selection bas ed on genetic signs are presently considered as human rights violation. On the other hand, to medically inform an individual with certain genetic characteristics about possible unfavorable health effects due to occupational hazard has little effect. Finally, a vast number of polymorphic genes in human genome (at least 30%) hampers accounting for all possible factors of genetic predisposition to the increasing number of environmental factors. Therefore, the current situation proves it appropriate to develop the new approach to account for genetic predisposition of individuals that would be free of flaws considered above. A possible basis for such an approach is the assessment of genotype specific relative risk (G.S.R.R.) that accounts for genetic predisposition (susceptibility) of individuals to the effects of unfavorable factors. The study used results from 65 studies. This effort was undertaken to study the association between 32 diseases and unfavorable effects and 17 genetic polymorphic systems. Data analysis included calculation of relative risk (R.R.) of specific diseases or effects development in individuals with different genotypes. Genotype-specific relative risk (G.S.R.R.) of diseases and unfavorable effects in individuals with 'sensitive' genotypes was calculated. Since about the third of genes in human genome are polymorphic, and therefore, a considerable number of genes can be involved in genetic predisposition of an individual to a specific unfavorable effect, an averaged G.S.R.R. of diseases and unfavorable effects was calculated for integral characteristics on

  20. Nevoid basal cell carcinoma syndrome. Profile of genetic and environmental factors in oncogenesis

    International Nuclear Information System (INIS)

    Howell, J.B.

    1984-01-01

    Nevoid basal cell carcinomas (NBCCs) are a prototype of a genetic form of basal cell carcinoma. These basal cell cancers, rather than being caused by genetic factors alone, are most likely the product of genetic and environmental factors. The NBCC syndrome provides a model for studying tumors induced by ionizing radiation and for viewing carcinogenesis as a multistage process explainable by a minimum of two steps. The interaction of genetic and environmental factors in producing tumors to which an individual is predisposed can be studied in patients with the NBCC syndrome and childhood medulloblastoma that was treated by radiation therapy. Individuals with the NBCC syndrome represent a special subgroup with a hereditary predisposition to basal cell carcinoma in whom ionizing radiation may supply the subsequent mutation necessary for tumor development. The genetically altered epidermis underlying the palm and sole pits found in patients with the syndrome represents basal cell carcinoma in situ from which basal cell carcinomas develop, albeit infrequently. The restrained biologic behavior of most of these tumors contrasts with the usual destructive behavior of the NBCCs of the head and neck in the same patient

  1. Local-regional control in breast cancer patients with a possible genetic predisposition

    International Nuclear Information System (INIS)

    Freedman, Laura M.; Buchholz, Thomas A.; Thames, Howard D.; Strom, Eric A.; McNeese, Marsha D.; Hortobagyi, Gabriel N.; Singletary, S. Eva; Heaton, Keith M.; Hunt, Kelly K.

    2000-01-01

    %, respectively. Conclusions: Patients with a possible genetic predisposition to breast cancer had low 5-year rates of local recurrence when treated with breast conserving surgery and radiation, but the local failure rate exceeded 50% when radiation was omitted. Our data are consistent with the hypothesis that patients with an underlying genetic predisposition develop cancers with radiosensitive phenotypes

  2. Genetic Risk for Alcoholic Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Flair José Carrilho

    2011-06-01

    Full Text Available In recent years many studies have examined the genetic predisposition to pancreatic diseases. Pancreatic disease of an alcoholic etiology was determined to be a multi-factorial disease, where environmental factors interact with the genetic profile of the individual. In this review we discuss the main results from studies examining the frequency of genetic mutations in alcoholic chronic pancreatitis.

  3. Isotretinoin as a Possible Environmental Trigger to Autoimmunity in Genetically Susceptible Patients

    Directory of Open Access Journals (Sweden)

    Jocelyn Nugroho

    2017-01-01

    Full Text Available Introduction. Isotretinoin is commonly used to treat cystic acne. Definitive mechanisms of action for isotretinoin are not known though despite many side effects having been documented. Various case reports have noted autoimmune diseases succeeding isotretinoin treatment. Case Report. A 16-year-old female presents with symptoms of tremors, lack of focus, sleeplessness, emotional liability, bulging eyes, loose stools, heat intolerance, and missed menstrual periods. Symptoms manifested shortly after the patient finished a course of oral isotretinoin treatment for acne. Physical exam showed resting tremors, bilateral proptosis, hyperactivity, and rapid speech. A diagnosis of Graves’ Disease was made by correlating symptoms, physical exam findings, ultrasound, and positive family history of autoimmune thyroid disease. Conclusion. Emergence of autoimmune thyroid diseases depends upon genetic predisposition and environmental triggers. Mechanism of action for isotretinoin is not known but the drug may play a role in triggering autoimmunity in genetically susceptible individuals.

  4. Genetic predisposition of donors affects the allograft outcome in kidney transplantation; polymorphisms of stromal-derived factor-1 and CXC receptor 4.

    Directory of Open Access Journals (Sweden)

    Jung Pyo Lee

    Full Text Available Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1 [rs1801157 (G>A] and CXC receptor 4 (CXCR4 [rs2228014 (C>T] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG (P  = 0.005. Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20-0.76, P = 0.006. CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (P = 0.001. This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.I = 1.19-7.60; P = 0.020. The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.

  5. Constitutional aneuploidy and cancer predisposition.

    Science.gov (United States)

    Ganmore, Ithamar; Smooha, Gil; Izraeli, Shai

    2009-04-15

    Constitutional aneuploidies are rare syndromes associated with multiple developmental abnormalities and the alterations in the risk for specific cancers. Acquired somatic chromosomal aneuploidies are the most common genetic aberrations in sporadic cancers. Thus studies of these rare constitutional aneuploidy syndromes are important not only for patient counseling and clinical management, but also for deciphering the mechanisms by which chromosomal aneuploidy affect cancer initiation and progression. Here we review the major constitutional aneuploidy syndromes and suggest some general mechanisms for the associated cancer predisposition.

  6. Effects of early life trauma are dependent on genetic predisposition: a rat study

    Directory of Open Access Journals (Sweden)

    Russell Vivienne A

    2011-05-01

    Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive

  7. Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry.

    Science.gov (United States)

    Cetica, Valentina; Sieni, Elena; Pende, Daniela; Danesino, Cesare; De Fusco, Carmen; Locatelli, Franco; Micalizzi, Concetta; Putti, Maria Caterina; Biondi, Andrea; Fagioli, Franca; Moretta, Lorenzo; Griffiths, Gillian M; Luzzatto, Lucio; Aricò, Maurizio

    2016-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. This work aims to further our understanding of the pathogenic bases of this rare condition based on an analysis of our 25 years of experience. From our registry, we have analyzed a total of 500 unselected patients with HLH. Biallelic pathogenic mutations defining FHL were found in 171 (34%) patients; the proportion of FHL was much higher (64%) in patients given a diagnosis during the first year of life. Taken together, mutations of the genes PRF1 (FHL2) and UNC13D (FHL3) accounted for 70% of cases of FHL. Overall, a genetic diagnosis was possible in more than 90% of our patients with FHL. Perforin expression and the extent of degranulation have been more useful for diagnosing FHL than hemophagocytosis and the cytotoxicity assay. Of 281 (56%) patients classified as having "sporadic" HLH, 43 had monoallelic mutations in one of the FHL-defining genes. Given this gene dosage effect, FHL is not strictly recessive. We suggest that the clinical syndrome HLH generally results from the combined effects of an exogenous trigger and genetic predisposition. Within this combination, different weights of exogenous and genetic factors account for the wide disease spectrum that ranges from HLH secondary to severe infection to FHL. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population.

    Science.gov (United States)

    Karaca, Sefayet; Erge, Sema; Cesuroglu, Tomris; Polimanti, Renato

    2016-06-01

    Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Disentangling the Importance of Psychological Predispositions and Social Constructions in the Organization of American Political Ideology.

    Science.gov (United States)

    Verhulst, Brad; Hatemi, Peter K; Eaves, Lindon J

    2012-06-01

    Ideological preferences within the American electorate are contingent on both the environmental conditions that provide the content of the contemporary political debate and internal predispositions that motivate people to hold liberal or conservative policy preferences. In this article we apply Jost, Federico, and Napier's (2009) top-down/bottom-up theory of political attitude formation to a genetically informative population sample. In doing so, we further develop the theory by operationalizing the top-down pathway to be a function of the social environment and the bottom-up pathway as a latent set of genetic factors. By merging insights from psychology, behavioral genetics, and political science, we find strong support for the top-down/bottom-up framework that segregates the two independent pathways in the formation of political attitudes and identifies a different pattern of relationships between political attitudes at each level of analysis.

  10. Breed-Predispositions to Cancer in Pedigree Dogs

    Science.gov (United States)

    Dobson, Jane M.

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. PMID:23738139

  11. Genes, Culture and Conservatism-A Psychometric-Genetic Approach.

    Science.gov (United States)

    Schwabe, Inga; Jonker, Wilfried; van den Berg, Stéphanie M

    2016-07-01

    The Wilson-Patterson conservatism scale was psychometrically evaluated using homogeneity analysis and item response theory models. Results showed that this scale actually measures two different aspects in people: on the one hand people vary in their agreement with either conservative or liberal catch-phrases and on the other hand people vary in their use of the "?" response category of the scale. A 9-item subscale was constructed, consisting of items that seemed to measure liberalism, and this subscale was subsequently used in a biometric analysis including genotype-environment interaction, correcting for non-homogeneous measurement error. Biometric results showed significant genetic and shared environmental influences, and significant genotype-environment interaction effects, suggesting that individuals with a genetic predisposition for conservatism show more non-shared variance but less shared variance than individuals with a genetic predisposition for liberalism.

  12. Diagnosis of genetic predisposition for lactose intolerance by high resolution melting analysis.

    Science.gov (United States)

    Delacour, Hervé; Leduc, Amandine; Louçano-Perdriat, Andréa; Plantamura, Julie; Ceppa, Franck

    2017-02-01

    Lactose, the principle sugar in milk, is a disaccharide hydrolyzed by intestinal lactase into glucose and galactose, which are absorbed directly by diffusion in the intestine. The decline of lactase expression (or hypolactasia) in intestinal microvilli after weaning is a normal phenomenon in mammals known as lactase deficiency. It is observed in nearly 75% of the world population and is an inherited autosomal recessive trait with incomplete penetrance. It is caused by SNPs in a regulatory element for lactase gene. In Indo-European, lactase deficiency is associated with rs4982235 SNP (or -13910C>T). The aim of this study is to describe a method based on high resolution melting for rapidly detecting genetic predisposition to lactose intolerance. Analytical performance of the assay was assessed by evaluating within and betwwen-run precision and by comparing the results (n = 50 patients) obtained with the HRM assay to those obtained with the gold standard (Sanger sequencing of the region of interest). In silico prediction of HRM curves was performed to evaluate the potential impact of the other SNPs described within the PCR product on the HRM analytical performances. The assay has good performance (CV lactose intolerance.

  13. Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas

    OpenAIRE

    Chan, Sock Hoai; Lim, Weng Khong; Ishak, Nur Diana Binte; Li, Shao-Tzu; Goh, Wei Lin; Tan, Gek San; Lim, Kiat Hon; Teo, Melissa; Young, Cedric Ng Chuan; Malik, Simeen; Tan, Mann Hong; Teh, Jonathan Yi Hui; Chin, Francis Kuok Choon; Kesavan, Sittampalam; Selvarajan, Sathiyamoorthy

    2017-01-01

    Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13....

  14. Evidence for a heritable predisposition to Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Bateman Lucinda

    2011-05-01

    Full Text Available Abstract Background Chronic Fatigue Syndrome (CFS came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV or other murine leukemia related retroviruses (MLV might also suggest underlying genetic implications within the host immune system. Methods We present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases. Results We observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p Conclusions These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.

  15. Clinical Assessment and Diagnosis of Germline Predisposition to Hematopoietic Malignancies: The University of Chicago Experience

    Directory of Open Access Journals (Sweden)

    Ami V. Desai

    2017-12-01

    Full Text Available With the increasing use of clinical genomics to guide cancer treatment and management, there is a rise in the identification of germline cancer predisposition syndromes and a critical need for patients with germline findings to be referred for surveillance and care. The University of Chicago Hematopoietic Malignancies Cancer Risk Team has established a unique approach to patient care for individuals with hereditary hematologic malignancies through close communication and coordination between our pediatric and adult programs. Dedicated program members, including physicians, nurses, genetic counselors, and clinical research assistants, screen individuals for cancer predisposition at initial diagnosis through survivorship, in addition to testing individuals with an established family history of a cancer predisposition syndrome. Sample procurement, such as a skin biopsy at the time of bone marrow aspirate/biopsy in individuals with a positive screen, has facilitated timely identification of clinical germline findings or has served as a pipeline for translational research. Our integrated translational research program has led to the identification of novel syndromes in collaboration with other investigators, which have been incorporated iteratively into our clinical pipeline. Individuals are referred for clinical assessment based on personal and family history, identification of variants in susceptibility genes via molecular tumor testing, and during evaluation for matched related allogeneic stem cell transplantation. Upon referral, genetic counseling incorporates education with mindfulness of the psychosocial issues surrounding germline testing at different ages. The training and role of genetic counselors continues to grow, with the discovery of new predisposition syndromes, in the age of improved molecular diagnostics and new models for service delivery, such as telemedicine. With the identification of new syndromes that may predispose individuals

  16. Myc contribution to γ-ray induced thymic lymphomas in mice of different genetic predispositions

    International Nuclear Information System (INIS)

    Sato, Toshihiro

    2008-01-01

    Myc gene has been suggested to be one of radiation targets in early genesis of γ ray-induced thymic lymphoma where Myc trisomy often occurs, and Myc activation results in p53 activation and apoptosis. The purpose of this study is to see the effects of radiation and mutation on Myc activation in the mouse. The lymphoma was induced by a single exposure of 3 Gy γ ray in BALB/c Bcl11b/Rit+/- and MSM p53-/- mice at 4 weeks after birth and by 4 weekly exposures of 2.5 Gy in p53+/- mouse. Genetic allele analysis for trisomy identification in the lymphoma was done by quantitative PCR using brain DNA as a control. Myc trisomy was found in the lymphoma of p53+/- mouse in 62% (23/37 animals) and of p53+/+, 66% (23/25), a similar frequency, suggesting that the target of radiation was not only the Myc activation. In addition, Myc trisomy frequency was 15% (4/27) in the lymphoma of Bcl11b+/+p53+/- and 36% (9/25), in heterozygote Bcl11b+/-. This finding suggested that the functional failure of Bcl11b reduced the contribution of Myc trisomy to the genesis. It was concluded that contribution of Myc trisomy to genesis of the lymphoma was dependent on genetic predisposition, and Myc-activated-, Bcl11b/Rit1-signal pathways played a parallel role in the genesis. (R.T.)

  17. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

    DEFF Research Database (Denmark)

    Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel

    2018-01-01

    BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA...... and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA...... elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV...

  18. Genetic predisposition to Parkinson's disease

    DEFF Research Database (Denmark)

    Halling, Jónrit; Petersen, Maria Skaalum; Grandjean, Philippe

    2008-01-01

    OBJECTIVE: To investigate whether the genetic variants of CYP2D6 and HFE are more frequent in Parkinson's disease (PD) patients compared with controls in a population where the prevalence of these variants and PD are increased. METHODS: Blood samples were collected from 79 PD patients and 154...

  19. Unifying diseases from a genetic point of view: the example of the genetic theory of infectious diseases.

    Science.gov (United States)

    Darrason, Marie

    2013-08-01

    In the contemporary biomedical literature, every disease is considered genetic. This extension of the concept of genetic disease is usually interpreted either in a trivial or genocentrist sense, but it is never taken seriously as the expression of a genetic theory of disease. However, a group of French researchers defend the idea of a genetic theory of infectious diseases. By identifying four common genetic mechanisms (Mendelian predisposition to multiple infections, Mendelian predisposition to one infection, and major gene and polygenic predispositions), they attempt to unify infectious diseases from a genetic point of view. In this article, I analyze this explicit example of a genetic theory, which relies on mechanisms and is applied only to a specific category of diseases, what we call "a regional genetic theory." I have three aims: to prove that a genetic theory of disease can be devoid of genocentrism, to consider the possibility of a genetic theory applied to every disease, and to introduce two hypotheses about the form that such a genetic theory could take by distinguishing between a genetic theory of diseases and a genetic theory of Disease. Finally, I suggest that network medicine could be an interesting framework for a genetic theory of Disease.

  20. ANALYSIS OF ACE, ACTN3, ENOS, PPARG, PPARA, HIF-15, PPARGC1B GENE POLYMORPHISMS FOR DETERMINATION A GENETIC PREDISPOSITION TO A VARIETY OF SPORTS

    Directory of Open Access Journals (Sweden)

    S. B. Drozdovska

    2013-05-01

    Full Text Available To establishing the possibility of assessing genetic iinherited predisposition to various sports, the differences in the distribution of genotypes of the complex polymorphisms in groups of athletes, specializing in sports with different types of energy supply of muscular work were studied. The paper examined the DNA 332 persons, of which 110 athletes involved in speed- power sports, 85 - in endurance sports , 51 - in sports that require a combination of strength and endurance, 86 - with no experience regular exercise.

  1. Consequences of diagnosing a tumor predisposition syndrome in children with cancer: A literature review

    NARCIS (Netherlands)

    Postema, Floor A. M.; Hopman, Saskia M. J.; Hennekam, Raoul C.; Merks, Johannes H. M.

    2018-01-01

    Up to 8.5% of children with cancer have a genetic cause for their cancer: a tumor predisposition syndrome (TPS). Diagnosing a TPS is of great importance, as it may have major consequences for clinical care. Patients with TPSs require specific monitoring and management. We present an overview of the

  2. The genetics of diabetes

    Directory of Open Access Journals (Sweden)

    Barjaktarović Nada

    2007-01-01

    Full Text Available Pathogenesis of diabetes is still a mystery for medicine, the real challenge currently being the identification of genetic factors and specific mutations that cause the disease. Heterogeneity of diabetes hampers research, only a few loci inside the human genome being correlated with predisposition for disease till now. Insulin-dependent diabetes - IDDM (T1DM develops through autoimmune destruction of pancreatic beta cells. HLA complex on the short arm of chromosome 6 (6p21, where very important genes responsible for immunological condition of the person are located, plays a very important role in genetic predisposition for T1DM. Beside this region, there are also other loci in the human genome (on chromosomes 1, 2 and 11 where a correlation with T1DM has been shown. Correlation between HLA systems and T1DM was first described for class I alleles, but recently attention has been drawn to class II loci which seem to be the cause of primary predisposition for T1DM. In the case of non-insulin-dependent diabetes - NIDDM (T2DM, the situation proved to be even more complex. Only a few genetic loci on chromosomes 11, 13 and 20 and MODY variant on chromosomes 7 and 12 have been identified by now. There are two theories about genetic basis of T2DM: the first stipulates that the genetic predisposition is determined through numerous loci, each individually responsible for a small part of predisposition; the second claims that there are a limited number of "major" genes probably functioning on a polygenic basis. Further research in this area is definitely needed to enable an accurate calculation of the risks of the disease and possible consequences during a lifetime of a person.

  3. Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.

    Science.gov (United States)

    Ussar, Siegfried; Griffin, Nicholas W; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I; Kahn, C Ronald

    2015-09-01

    Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Breed predisposition to canine gastric carcinoma

    DEFF Research Database (Denmark)

    Seim-Wikse, Tonje; Jörundsson, Einar; Nødtvedt, Ane

    2013-01-01

    Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The ai...

  5. Molecular Characterization of Melanoma Cases in Denmark Suspected of Genetic Predisposition

    DEFF Research Database (Denmark)

    Wadt, Karin A. W.; Aoude, Lauren G.; Krogh, Lotte

    2015-01-01

    Both environmental and host factors influence risk of cutaneousmelanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E3...... cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma....

  6. The genetic basis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    A. A. Tappakhov

    2017-01-01

    Full Text Available Parkinson's disease (PD is a multifactorial disease that develops in the presence of both genetic and environmental factors. In recent years, there has been sufficient information on the role of genetic predisposition in the development of not only familial cases, but also sporadic ones. A hereditary burden in PD may not be traced in cases of recessive inheritance with a low gene penetrance, as well as in a patient's death before the onset of the disease. Active introduction of molecular genetic methods, including next generation sequencing, can annually identify new gene mutations that underlie sporadic PD cases. This paper provides an overview of the current literature on the genetic aspects of PD with emphasis on the ethnic characteristics of the disease.

  7. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lacko, Martin [Department of Otorhinolaryngology—Head and Neck Surgery, Maastricht University Medical Center, Maastricht (Netherlands); Braakhuis, Boudewijn J.M. [Department of Otolaryngology—Head and Neck Surgery, VU University Medical Center, Amsterdam (Netherlands); Sturgis, Erich M. [Department of Head and Neck Surgery and Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Boedeker, Carsten C. [Department of Otorhinolaryngology—Head and Neck Surgery, Albert-Ludwigs-University, Freiburg, Germany and Department of Otorhinolaryngology - Head and Neck Surgery, HELIOS Hanseklinikum Stralsund, Stralsund (Germany); Suárez, Carlos [Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo (Spain); Instituto Universitario de Oncología del Principado de Asturias, Oviedo (Spain); Rinaldo, Alessandra; Ferlito, Alfio [ENT Clinic, University of Udine, Udine (Italy); Takes, Robert P., E-mail: robert.takes@radboudumc.nl [Department of Otolaryngology—Head and Neck Surgery, Radboud University Nijmegen Medical Center, Nijmegen (Netherlands)

    2014-05-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed.

  8. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.; Boedeker, Carsten C.; Suárez, Carlos; Rinaldo, Alessandra; Ferlito, Alfio; Takes, Robert P.

    2014-01-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives of research on genetic susceptibility in HNSCC are discussed

  9. Genetics Home Reference: rhabdoid tumor predisposition syndrome

    Science.gov (United States)

    ... rare type of ovarian cancer called small cell cancer of the ovary hypercalcemic type (SCCOHT). Related Information What does it mean if a disorder seems to run in my family? What is the prognosis of a genetic condition? Genetic ... Cancer Institute: Childhood Central Nervous System Atypical Teratoid/Rhabdoid ...

  10. Manipulations in maternal environment reverse periodontitis in genetically predisposed rats.

    NARCIS (Netherlands)

    Sluyter, F.; Breivik, T.; Cools, A.R.

    2002-01-01

    The predisposition to develop periodontitis is partly genetically determined in humans as well as in animals. Here we demonstrate, however, that early manipulations in the maternal environment of an animal (rat) model of periodontitis can fully reverse the genetic predisposition to develop

  11. Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition

    OpenAIRE

    Husted, Janice A.; Ahmed, Rashid; Chow, Eva W.C.; Brzustowicz, Linda M.; Bassett, Anne S.

    2012-01-01

    There are few studies of environmental factors in familial forms of schizophrenia. We investigated whether childhood adversity or environmental factors were associated with schizophrenia in a familial sample where schizophrenia is associated with the NOSA1P gene. We found that a cumulative adversity index including childhood illness, family instability and cannabis use was significantly associated with narrow schizophrenia, independent of NOSA1P risk genotype, previously measured childhood tr...

  12. Genetic and environmental influence on asthma

    DEFF Research Database (Denmark)

    Skadhauge, L.R.; Christensen, Kaare; Kyvik, Kirsten Ohm

    1999-01-01

    The aim of this study was to estimate the relative influence of genetic and environmental factors on the aetiology of asthma. The classic twin study design was used to analyse data on self-reported asthma obtained by a questionnaire mailed to 34,076 individuals, aged 12-41 yrs and originating from...... in the monozygotic than in the dizygotic twins. Using biometric modelling, a model including additive genetic and nonshared environmental effects provided the best overall fit to the data. According to this model, 73% of the variation in liability to asthma was explained by genetic factors. No sex difference or age......-dependency in the magnitude of genetic effects was observed. The biometric analysis emphasized a major influence of genetic factors in the aetiology of asthma. However, a substantial part of the variation in liability to asthma is due to the impact of environmental factors specific to the individual. There is no evidence...

  13. Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference

    DEFF Research Database (Denmark)

    Olsen, Nanna J; Ängquist, Lars; Larsen, Sofus C

    2016-01-01

    circumference (WC), or the waist- To-hip ratio adjusted for BMI (WHRBMI), the following 4 genetic predisposition scores (GRSs) were constructed: A complete genetic predisposition score including all 50 single nucleotide polymorphisms (GRSComplete), a genetic predisposition score including BMI- Associated single...

  14. Environmental change, phenotypic plasticity, and genetic compensation.

    Science.gov (United States)

    Grether, Gregory F

    2005-10-01

    When a species encounters novel environmental conditions, some phenotypic characters may develop differently than in the ancestral environment. Most environmental perturbations of development are likely to reduce fitness, and thus selection would usually be expected to favor genetic changes that restore the ancestral phenotype. I propose the term "genetic compensation" to refer to this form of adaptive evolution. Genetic compensation is a subset of genetic accommodation and the reverse of genetic assimilation. When genetic compensation has occurred along a spatial environmental gradient, the mean trait values of populations in different environments may be more similar in the field than when representatives of the same populations are raised in a common environment (i.e., countergradient variation). If compensation is complete, genetic divergence between populations may be cryptic, that is, not detectable in the field. Here I apply the concept of genetic compensation to three examples involving carotenoid-based sexual coloration and then use these and other examples to discuss the concept in a broader context. I show that genetic compensation may lead to a cryptic form of reproductive isolation between populations evolving in different environments, may explain some puzzling cases in which heritable traits exposed to strong directional selection fail to show the expected evolutionary response, and may complicate efforts to monitor populations for signs of environmental deterioration.

  15. Manipulations in Maternal Environment Reverse Periodontitis in Genetically Predisposed Rats

    Science.gov (United States)

    Sluyter, Frans; Breivik, Torbjørn; Cools, Alexander

    2002-01-01

    The predisposition to develop periodontitis is partly genetically determined in humans as well as in animals. Here we demonstrate, however, that early manipulations in the maternal environment of an animal (rat) model of periodontitis can fully reverse the genetic predisposition to develop periodontitis at adult age. PMID:12093700

  16. Genetic and environmental factors affecting birth size variation

    DEFF Research Database (Denmark)

    Yokoyama, Yoshie; Jelenkovic, Aline; Hur, Yoon-Mi

    2018-01-01

    Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia......) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling....... Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased...

  17. The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer.

    Science.gov (United States)

    Esteban-Jurado, Clara; Franch-Expósito, Sebastià; Muñoz, Jenifer; Ocaña, Teresa; Carballal, Sabela; López-Cerón, Maria; Cuatrecasas, Miriam; Vila-Casadesús, Maria; Lozano, Juan José; Serra, Enric; Beltran, Sergi; Brea-Fernández, Alejandro; Ruiz-Ponte, Clara; Castells, Antoni; Bujanda, Luis; Garre, Pilar; Caldés, Trinidad; Cubiella, Joaquín; Balaguer, Francesc; Castellví-Bel, Sergi

    2016-10-01

    Colorectal cancer (CRC) is one of the most common neoplasms in the world. Fanconi anemia (FA) is a very rare genetic disease causing bone marrow failure, congenital growth abnormalities and cancer predisposition. The comprehensive FA DNA damage repair pathway requires the collaboration of 53 proteins and it is necessary to restore genome integrity by efficiently repairing damaged DNA. A link between FA genes in breast and ovarian cancer germline predisposition has been previously suggested. We selected 74 CRC patients from 40 unrelated Spanish families with strong CRC aggregation compatible with an autosomal dominant pattern of inheritance and without mutations in known hereditary CRC genes and performed germline DNA whole-exome sequencing with the aim of finding new candidate germline predisposition variants. After sequencing and data analysis, variant prioritization selected only those very rare alterations, producing a putative loss of function and located in genes with a role compatible with cancer. We detected an enrichment for variants in FA DNA damage repair pathway genes in our familial CRC cohort as 6 families carried heterozygous, rare, potentially pathogenic variants located in BRCA2/FANCD1, BRIP1/FANCJ, FANCC, FANCE and REV3L/POLZ. In conclusion, the FA DNA damage repair pathway may play an important role in the inherited predisposition to CRC.

  18. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    Science.gov (United States)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos; Brook, Mark N; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; Dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C; Hopper, John L; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A; Jud, Sebastian M; Ekici, Arif B; Beckmann, Matthias W; Kerin, Michael J; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Investigators, Kconfab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; McLean, Catriona A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline M; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J; Sherman, Mark E; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-04-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at Plobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

  19. Classical and molecular genetics of malignant melanoma and dysplastic naevi

    International Nuclear Information System (INIS)

    Traupe, H.; Macher, E.

    1988-01-01

    The authors conclude that the prevailing concept of monogenic autosomaldominant inheritance of dysplastic naevi and familial melanoma is not compatible with the principles of formal (Mendelian) genetics. The concept of polygenic inheritance offers instead a sound basis to explain familial aggregation of dysplastic naevi and melanoma. The various genes involved have not yet been identified at the molecular level. The recent advances made possible by modern DNA technology have given us a new view of carcinogenesis. In human malignant melanoma, chromosomes 1, 6, 7 are of particular interest and oncogenes located on these chromosomes may be involved with the initiation, promotion and progression of melanoma. Carcinogenesis is viewed as a multistep process and even tumour initiation requires the input of at least two independent oncogenes. Molecular genetics thus adds an important argument for the existence of a polygenic predisposition to melanoma. The concept of polygenic inheritance is not restricted to familial melanoma, but implies that all melanomas basically share the same predisposition and are due to similar genetic mechanisms. In some patients an inherited genetic predisposition is of great importance, whereas in others (the majority) environmental factors (e.g. UV-light-induced mutations) will be the cause of initial steps in the malignant transformation. The concept of polygenic inheritance has consequences for the management of our patients. In contrast to simple Mendelian inheritance, the risk for dysplastic naevi and melanoma is not constantly 50%, but increases with the number of family members already affected. Persons belonging to families with more that 2 affected close relatives should be considered at high risk regardless of the dysplastic naevus status. Strict surveillance of this patient group is warranted for melanoma prevention

  20. Association between Maternal Fish Consumption and Gestational Weight Gain: Influence of Molecular Genetic Predisposition to Obesity.

    Directory of Open Access Journals (Sweden)

    Sofus C Larsen

    Full Text Available Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG, and whether this relationship depends on genetic makeup.To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity.A nested case-cohort study based on the Danish National Birth Cohort (DNBC sampling the most obese women (n = 990 and a random sample of the remaining participants (n = 1,128. Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC (n = 4,841. We included 32 body mass index (BMI associated single nucleotide polymorphisms (SNPs and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS. Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined.In the DNBC, each portion/week (150 g of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01. For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01 per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings.We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs.

  1. Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity - a prospective study of three independent cohorts

    Science.gov (United States)

    2014-01-01

    Background Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity. Hence, we examined whether dietary ascorbic acid, possibly in interaction with the genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHR), associates with subsequent annual changes in weight (∆BW) and waist circumference (∆WC). Methods A total of 7,569 participants’ from MONICA, the Diet Cancer and Health study and the INTER99 study were included in the study. We combined 50 obesity associated single nucleotide polymorphisms (SNPs) in four genetic scores: a score of all SNPs and a score for each of the traits (BMI, WC and WHR) with which the SNPs associate. Linear regression was used to examine the association between ascorbic acid intake and ΔBW or ΔWC. SNP-score × ascorbic acid interactions were examined by adding product terms to the models. Results We found no significant associations between dietary ascorbic acid and ∆BW or ∆WC. Regarding SNP-score × ascorbic acid interactions, each additional risk allele of the 14 WHR associated SNPs associated with a ∆WC of 0.039 cm/year (P = 0.02, 95% CI: 0.005 to 0.073) per 100 mg/day higher ascorbic acid intake. However, the association to ∆WC only remained borderline significant after adjustment for ∆BW. Conclusion In general, our study does not support an association between dietary ascorbic acid and ∆BW or ∆WC, but a diet with a high content of ascorbic acid may be weakly associated to higher WC gain among people who are genetically predisposed to a high WHR. However, given the quite limited association any public health relevance is questionable. PMID:24886192

  2. Environment Changes Genetic Effects on Respiratory Conditions and Allergic Phenotypes

    DEFF Research Database (Denmark)

    Song, Yong; Schwager, Michelle J; Backer, Vibeke

    2017-01-01

    The prevalence of asthma and allergic diseases is disproportionately distributed among different populations, with an increasing trend observed in Western countries. Here we investigated how the environment affected genotype-phenotype association in a genetically homogeneous, but geographically...... separated population. We evaluated 18 single nucleotide polymorphisms (SNPs) corresponding to 8 genes (ADAM33, ALOX5, LT-α, LTC4S, NOS1, ORMDL3, TBXA2R and TNF-α), the lung function and five respiratory/allergic conditions (ever asthma, bronchitis, rhinitis, dermatitis and atopy) in two populations of Inuit......-phenotype associations relating to bronchitis and allergy susceptibility are dependent on the environment and that environmental factors/lifestyles modify genetic predisposition and change the genetic effects on diseases....

  3. Environmental chemical mutagens and genetic risks: Lessons from radiation genetics

    International Nuclear Information System (INIS)

    Sankaranarayanan, K.

    1996-01-01

    The last three decades have witnessed substantial progress in the development and use of a variety of in vitro and in vivo assay systems for the testing of environmental chemicals which may pose a mutagenic hazard to humans. This is also true of basic studies in chemical mutagenesis on mechanisms, DNA repair, molecular dosimetry, structure-activity relationships, etc. However, the field of quantitative evaluation of genetic risks of environmental chemicals to humans is still in it infancy. This commentary addresses the question of how our experience in estimating genetic risks of exposure to ionizing radiation can be helpful in similar endeavors with environmental chemical mutagens. 24 refs., 3 tabs

  4. On the influence of abiotic stress conditions on growth of barley and bean and their predisposition for pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Oerke, E.C.; Schoenbeck, F.

    1986-01-01

    Shorttime changes of environmental conditions stressed barley and bean and affected plant growth and their predisposition for various pathogens. Moderate stress intensities as low or high temperatures, water or light deficits, increased the susceptibility to Erysiphe graminis var. hordei or Uromyces phaseoli and reduced disease level of spot blotch caused by Cochliobolus sativus, respectively. There was only little effect on plant growth in that case. Intensive stress as a result of combinations of unfavorable environmental conditions or longtime continuance of moderate stress reduced the plant growth and turned the predisposing effect to the opposite: after the treatment, plants were more resistent to diseases caused by biotrophic fungi, whereas there was increased susceptibility to the perthotrophic fungus. High intensities of fertilization acted as an additional stress and intensified the plant reaction to environmental alterations. The variation of the predisposition is discussed in relation to stress intensity.

  5. Impact of behavioral genetic evidence on the adjudication of criminal behavior.

    Science.gov (United States)

    Appelbaum, Paul S; Scurich, Nicholas

    2014-01-01

    Recent advances in behavioral genetics suggest a modest relationship among certain gene variants, early childhood experiences, and criminal behavior. Although scientific research examining this link is still at an early stage, genetic data are already being introduced in criminal trials. However, the extent to which such evidence is likely to affect jurors' decisions has not been explored. In the present study, a representative sample of the U.S. population (n = 250) received a vignette describing an apparently impulsive homicide, accompanied by one of four explanations of the defendant's impulsivity: childhood abuse, genetic predisposition, childhood abuse and genetic predisposition, or simple impulsive behavior. The participants were asked to identify the crime that the defendant had committed and to select an appropriate sentence range. Evidence of genetic predisposition did not affect the crime of which the defendant was convicted or the sentence. However, participants who received the abuse or genetic + abuse explanation imposed longer prison sentences. Paradoxically, the genetic and genetic + abuse conditions engendered the greatest fear of the defendant. These findings should allay concerns that genetic evidence in criminal adjudications will be overly persuasive to jurors, but should raise questions about the impact of genetic attributions on perceptions of dangerousness.

  6. Generalizing genetical genomics: getting added value from environmental perturbation.

    Science.gov (United States)

    Li, Yang; Breitling, Rainer; Jansen, Ritsert C

    2008-10-01

    Genetical genomics is a useful approach for studying the effect of genetic perturbations on biological systems at the molecular level. However, molecular networks depend on the environmental conditions and, thus, a comprehensive understanding of biological systems requires studying them across multiple environments. We propose a generalization of genetical genomics, which combines genetic and sensibly chosen environmental perturbations, to study the plasticity of molecular networks. This strategy forms a crucial step toward understanding why individuals respond differently to drugs, toxins, pathogens, nutrients and other environmental influences. Here we outline a strategy for selecting and allocating individuals to particular treatments, and we discuss the promises and pitfalls of the generalized genetical genomics approach.

  7. Advances in genetics and immunology: the importance of basic research to prevention of occupational diseases

    International Nuclear Information System (INIS)

    Omenn, G.S.

    1984-01-01

    Differences among workers in susceptibility to workplace exposures to environmental agents such as metals, ultraviolet radiation, and x-radiation are discussed. The distinction is made between the need for (1) monitoring for effects on the genetic material (genetic toxicology) and (2) screening for predisposing inherited traits (eco-genetics). Genetically-determined differences in susceptibility are discussed in relation to mechanisms of metabolism and of target sites. While there is not enough evidence to support routine genetic screening at this time there is common agreement that several promising areas for research on potential genetic predispositions warrant careful study. There is also reassuring evidence that productive relationships for research can be established among unions, management, and universities. 56 references, 3 figures, 7 tables

  8. Genetic and Environmental Continuity in Personality Development: A Meta-Analysis

    Science.gov (United States)

    Briley, Daniel A.; Tucker-Drob, Elliot M.

    2014-01-01

    The longitudinal stability of personality is low in childhood, but increases substantially into adulthood. Theoretical explanations for this trend differ in the emphasis placed on intrinsic maturation and socializing influences. To what extent does the increasing stability of personality result from the continuity and crystallization of genetically influenced individual differences, and to what extent does the increasing stability of life experiences explain increases in personality trait stability? Behavioral genetic studies, which decompose longitudinal stability into sources associated with genetic and environmental variation, can help to address this question. We aggregated effect sizes from 24 longitudinal behavioral genetic studies containing information on a total of 21,057 sibling pairs from six types that varied in terms of genetic relatedness and ranged in age from infancy to old age. A combination of linear and nonlinear meta-analytic regression models were used to evaluate age-trends in levels of heritability and environmentality, stabilities of genetic and environmental effects, and the contributions of genetic and environmental effects to overall phenotypic stability. Both the genetic and environmental influences on personality increase in stability with age. The contribution of genetic effects to phenotypic stability is moderate in magnitude and relatively constant with age, in part because of small-to-moderate decreases in the heritability of personality over child development that offset increases in genetic stability. In contrast, the contribution of environmental effects to phenotypic stability increases from near-zero in early childhood to moderate in adulthood. The lifespan trend of increasing phenotypic stability, therefore, predominantly results from environmental mechanisms. PMID:24956122

  9. Environmental carcinogenesis and genetic variability

    International Nuclear Information System (INIS)

    Knudsen, A.G. Jr

    1977-01-01

    It was found that carcinogenesis in man may involve the interaction of genetic and environmental forces, and that mutation, whether germinal or somatic, seems to be involved in the origin of many, perhaps all cancers. The cancers of man may be visualized as occurring in four groups of individuals according to whether (1) neither genetic nor environmental factors are dominant, i.e. 'background' or 'spontaneous' cancer, (2) heredity alone is dominant, (3) environment alone is important, or (4) both are operating (Knudsen, 1977). The last two groups together are widely thought to contribute 70-80% of cancer cases in the United States; the relative contribution of each group is a major question to be answered

  10. Postirradiation sarcoma in retinoblastoma. Induction or predisposition

    International Nuclear Information System (INIS)

    Schwarz, M.B.; Burgess, L.P.; Fee, W.E. Jr.; Donaldson, S.S.

    1988-01-01

    An alarmingly high rate of postirradiation sarcomas following treatment for retinoblastoma has been described in the literature. We present four new cases and report 57 others from the English literature. Osteogenic sarcoma was the predominant histologic type (58%), followed by fibrosarcoma (21%) and various other sarcomas (21%). The average latency period between irradiation and development of the second primary (sarcoma) was 12.4 years. Irrespective of irradiation, a genetic linkage between retinoblastoma and osteogenic sarcoma on the 13q14 chromosome is recognized. Through a pleiotropic effect of this same chromosome, a predisposition for other sarcomas may exist as well. Finally, a strong role for radiation induction is proposed for all of these postirradiation sarcomas. This is based on the increased number of sarcomas arising in the field of prior irradiation (sites uncharacteristic of spontaneously occurring primary sarcomas) and the prolonged latency periods.13 references

  11. Genetic and environmental continuity in personality development: a meta-analysis.

    Science.gov (United States)

    Briley, Daniel A; Tucker-Drob, Elliot M

    2014-09-01

    The longitudinal stability of personality is low in childhood but increases substantially into adulthood. Theoretical explanations for this trend differ in the emphasis placed on intrinsic maturation and socializing influences. To what extent does the increasing stability of personality result from the continuity and crystallization of genetically influenced individual differences, and to what extent does the increasing stability of life experiences explain increases in personality trait stability? Behavioral genetic studies, which decompose longitudinal stability into sources associated with genetic and environmental variation, can help to address this question. We aggregated effect sizes from 24 longitudinal behavioral genetic studies containing information on a total of 21,057 sibling pairs from 6 types that varied in terms of genetic relatedness and ranged in age from infancy to old age. A combination of linear and nonlinear meta-analytic regression models were used to evaluate age trends in levels of heritability and environmentality, stabilities of genetic and environmental effects, and the contributions of genetic and environmental effects to overall phenotypic stability. Both the genetic and environmental influences on personality increase in stability with age. The contribution of genetic effects to phenotypic stability is moderate in magnitude and relatively constant with age, in part because of small-to-moderate decreases in the heritability of personality over child development that offset increases in genetic stability. In contrast, the contribution of environmental effects to phenotypic stability increases from near zero in early childhood to moderate in adulthood. The life-span trend of increasing phenotypic stability, therefore, predominantly results from environmental mechanisms. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  12. The role of epigenetics in genetic and environmental epidemiology.

    Science.gov (United States)

    Ladd-Acosta, Christine; Fallin, M Daniele

    2016-02-01

    Epidemiology is the branch of science that investigates the causes and distribution of disease in populations in order to provide preventative measures and promote human health. The fields of genetic and environmental epidemiology primarily seek to identify genetic and environmental risk factors for disease, respectively. Epigenetics is emerging as an important piece of molecular data to include in these studies because it can provide mechanistic insights into genetic and environmental risk factors for disease, identify potential intervention targets, provide biomarkers of exposure, illuminate gene-environment interactions and help localize disease-relevant genomic regions. Here, we describe the importance of including epigenetics in genetic and environmental epidemiology studies, provide a conceptual framework when considering epigenetic data in population-based studies and touch upon the many challenges that lie ahead.

  13. Genetic Analysis of Micro-environmental Plasticity in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Morgante, Fabio; Sorensen, Daniel A; Sørensen, Peter

    Quantitative genetic models recognize the potential for genotype by environment interaction, whereby different genotypes have different plastic responses to changes in macro-environmental conditions. Recently, it has been recognized that micro-environmental plasticity (‘residual’ variance) may also...... be genetically variable. This study utilized the Drosophila Genetic Reference Panel (DGRP) to accurately estimate the genetic variance of micro-environmental plasticity for chill coma recovery time and startle response. Estimates of broad sense heritabilities for both traits are substantial (from 0.51 to 0.......77), of the same order as the heritability at the level of the trait mean for startle response and even larger for chill coma recovery. Genome wide association analyses identified molecular variants (from 15 to 31 depending on the sex and the trait) associated with micro-environmental plasticity. These findings...

  14. Diagnostics of movement predispositions in fitnness centre

    OpenAIRE

    Vojtíšek, Petr

    2011-01-01

    Title: Diagnostics of movement predispositions in fitness Objectives: The objective of bachelor thesis is to summarize the findings of the initial diagnostics od movement predispositions in fitness and then serve as a resource for those interested in education in this field. The aim of the practical part of this work is to obtain information about the diagnostic methods used to assess physical assumptions in the fitness centers. Methods: In this thesis was used the method of analysis of scien...

  15. Sleep Reactivity and Insomnia: Genetic and Environmental Influences

    Science.gov (United States)

    Drake, Christopher L.; Friedman, Naomi P.; Wright, Kenneth P.; Roth, Thomas

    2011-01-01

    Study Objectives: Determine the genetic and environmental contributions to sleep reactivity and insomnia. Design: Population-based twin cohort. Participants: 1782 individual twins (988 monozygotic or MZ; 1,086 dizygotic or DZ), including 744 complete twin pairs (377 MZ and 367 DZ). Mean age was 22.5 ± 2.8 years; gender distribution was 59% women. Measurements: Sleep reactivity was measured using the Ford Insomnia Response to Stress Test (FIRST). The criterion for insomnia was having difficulty falling asleep, staying asleep, or nonrefreshing sleep “usually or always” for ≥ 1 month, with at least “somewhat” interference with daily functioning. Results: The prevalence of insomnia was 21%. Heritability estimates for sleep reactivity were 29% for females and 43% for males. The environmental variance for sleep reactivity was greater for females and entirely due to nonshared effects. Insomnia was 43% to 55% heritable for males and females, respectively; the sex difference was not significant. The genetic variances in insomnia and FIRST scores were correlated (r = 0.54 in females, r = 0.64 in males), as were the environmental variances (r = 0.32 in females, r = 0.37 in males). In terms of individual insomnia symptoms, difficulty staying asleep (25% to 35%) and nonrefreshing sleep (34% to 35%) showed relatively more genetic influences than difficulty falling asleep (0%). Conclusions: Sleep reactivity to stress has a substantial genetic component, as well as an environmental component. The finding that FIRST scores and insomnia symptoms share genetic influences is consistent with the hypothesis that sleep reactivity may be a genetic vulnerability for developing insomnia. Citation: Drake CL; Friedman NP; Wright KP; Roth T. Sleep reactivity and insomnia: genetic and environmental influences. SLEEP 2011;34(9):1179-1188. PMID:21886355

  16. [Inherited colorectal cancer predisposition syndromes identified in the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, Peru;].

    Science.gov (United States)

    Castro-Mujica, María del Carmen; Sullcahuamán-Allende, Yasser; Barreda-Bolaños, Fernando; Taxa-Rojas, Luis

    2014-04-01

    Colorectal cancer (CRC) is the fourth most common cancer in the world and is classified according to their origin in sporadic CRC (~ 70%) and genetic CRC (~ 30%), this latter involves cases of familial aggregation and inherited síndromes that predispose to CRC. To describe inherited CRC predisposition syndromes, polyposic and non-polyposic, identified in the Oncogenetics Unit at National Institute of Cancer Disease (INEN). A descriptive observational record from the attentions of the Oncogenetics Unit at INEN during 2009 to 2013. We included patients with personal or familiar history of CRC and/or colonic polyposis who were referred for clinical assessment to the Oncogenetics Unitat INEN. 59.3 % were female, 40.7 % male, 69.8% under 50 years old, 60.5% had a single CRC, 23.2% had more than one CRC or CRC associated with other extracolonic neoplasia and 32.6% had a familiar history of cancer with autosomal dominant inheritance. According to the clinical genetic diagnosis, 93.1% of the included cases were inherited syndromes that predispose to CRC, with 33.8% of colonic polyposis syndromes, 23.3% of hereditary nonpolyposis CRC syndromes (HNPCC) and 36.0% of CCRHNP probable cases. Clinical genetic evaluation of patients with personal or familiar history of CRC and/or colonic polyposis can identify inherited colorectal cancer predisposition syndromes and provide an appropriategenetic counseling to patients and relatives at risk, establishing guidelines to follow-up and prevention strategies to prevent morbidity and mortality by cancer.

  17. Validation of a clinical screening instrument for tumour predisposition syndromes in patients with childhood cancer (TuPS) : Protocol for a prospective, observational, multicentre study

    NARCIS (Netherlands)

    Postema, Floor A M; Hopman, Saskia M J; De Borgie, Corianne A J M; Hammond, Peter; Hennekam, Raoul C.; Merks, Johannes H M; Aalfs, Cora M.; Anninga, Jakob K.; Berger, Lieke P V; Bleeker, Fonnet E.; De Bont, Eveline S J M; Dommering, Charlotte J.; Van Eijkelenburg, Natasha K A; Van Den Heuvel-Eibrink, Marry M.; Jongmans, Marjolijn C J; Kors, Wijnanda A.; Letteboer, Tom G W; Loeffen, Jan L C M; Olderode-Berends, Maran J W; Wagner, Anja

    2017-01-01

    Introduction: Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half of the known TPSs are recognised during standard

  18. Genetic Influences on Conduct Disorder

    Science.gov (United States)

    Salvatore, Jessica E.; Dick, Danielle M.

    2016-01-01

    Conduct disorder (CD) is a moderately heritable psychiatric disorder of childhood and adolescence characterized by aggression toward people and animals, destruction of property, deceitfulness or theft, and serious violation of rules. Genome-wide scans using linkage and association methods have identified a number of suggestive genomic regions that are pending replication. A small number of candidate genes (e.g., GABRA2, MAOA, SLC6A4, AVPR1A) are associated with CD related phenotypes across independent studies; however, failures to replicate also exist. Studies of gene-environment interplay show that CD genetic predispositions also contribute to selection into higher-risk environments, and that environmental factors can alter the importance of CD genetic factors and differentially methylate CD candidate genes. The field’s understanding of CD etiology will benefit from larger, adequately powered studies in gene identification efforts; the incorporation of polygenic approaches in gene-environment interplay studies; attention to the mechanisms of risk from genes to brain to behavior; and the use of genetically informative data to test quasi-causal hypotheses about purported risk factors. PMID:27350097

  19. Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

    Science.gov (United States)

    Yurgelun, Matthew B; Allen, Brian; Kaldate, Rajesh R; Bowles, Karla R; Judkins, Thaddeus; Kaushik, Praveen; Roa, Benjamin B; Wenstrup, Richard J; Hartman, Anne-Renee; Syngal, Sapna

    2015-09-01

    Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. We performed germline analysis with a 25-gene, next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All patients had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain clinical significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing. Of the 1260 patients, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P = .0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%). In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many

  20. Genetic and environmental effects of mortality before age 70 years

    DEFF Research Database (Denmark)

    Petersen, Liselotte; Andersen, Per Kragh; Sørensen, Thorkild I.A.

    2008-01-01

    BACKGROUND:: There is a familial influence on risk of many diseases and on mortality in general, which, according to studies of twins, is due to a combination of genetic and environmental effects. Adoption studies, which rest on different assumptions, may also be used to estimate separately...... the genetic and environmental effects on rate of dying. METHODS:: The genetic influence on the rate of dying before age 70 years was investigated by estimation of the associations in total and cause-specific mortality of Danish adoptees and their biologic full and half siblings. Familial environmental...

  1. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

    Science.gov (United States)

    Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Evans, D Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Eccles, Diana; Jensen, Thomas; Osther, Palle J; van Asperen, Christi J; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Cook, Jackie; Rosario, Derek J; Buys, Saundra S; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet Gem; Teixeira, Manuel R; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-van den Enden, Apollonia Tjm; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J; Liljegren, Annelie; Harris, Marion; Adank, Muriel A; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Gadea, Neus; Brady, Angela F; Gallagher, David; van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; James, Paul A; Murphy, Declan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias; Murthy, Vedang; Copakova, Lucia; McGrath, John; Teo, Soo-Hwang; Strom, Sara; Kast, Karin; Leongamornlert, Daniel A; Chamberlain, Anthony; Pope, Jenny; Newlin, Anna C; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Castro, Elena; Dearnaley, David; Eyfjord, Jorunn; Falconer, Alison; Foster, Christopher S; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Lubinski, Jan; Grindedal, Eli Marie; McKinley, Joanne; Shackleton, Kylie; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Tricker, Karen; Moss, Sue; Kote-Jarai, Zsofia; Vickers, Andrew; Lilja, Hans; Helfand, Brian T; Eeles, Rosalind A

    2018-01-01

    Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l , PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

  2. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

    Science.gov (United States)

    Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel; Bancroft, Elizabeth; Vertosick, Emily; Dadaev, Tokhir; Brendler, Charles; Page, Elizabeth; Dias, Alexander; Evans, D Gareth; Rothwell, Jeanette; Maehle, Lovise; Axcrona, Karol; Richardson, Kate; Eccles, Diana; Jensen, Thomas; Osther, Palle J; van Asperen, Christi J; Vasen, Hans; Kiemeney, Lambertus A; Ringelberg, Janneke; Cybulski, Cezary; Wokolorczyk, Dominika; Hart, Rachel; Glover, Wayne; Lam, Jimmy; Taylor, Louise; Salinas, Monica; Feliubadaló, Lidia; Oldenburg, Rogier; Cremers, Ruben; Verhaegh, Gerald; van Zelst-Stams, Wendy A; Oosterwijk, Jan C; Cook, Jackie; Rosario, Derek J; Buys, Saundra S; Conner, Tom; Domchek, Susan; Powers, Jacquelyn; Ausems, Margreet GEM; Teixeira, Manuel R; Maia, Sofia; Izatt, Louise; Schmutzler, Rita; Rhiem, Kerstin; Foulkes, William D; Boshari, Talia; Davidson, Rosemarie; Ruijs, Marielle; Helderman-van den Enden, Apollonia TJM; Andrews, Lesley; Walker, Lisa; Snape, Katie; Henderson, Alex; Jobson, Irene; Lindeman, Geoffrey J; Liljegren, Annelie; Harris, Marion; Adank, Muriel A; Kirk, Judy; Taylor, Amy; Susman, Rachel; Chen-Shtoyerman, Rakefet; Pachter, Nicholas; Spigelman, Allan; Side, Lucy; Zgajnar, Janez; Mora, Josefina; Brewer, Carole; Gadea, Neus; Brady, Angela F; Gallagher, David; van Os, Theo; Donaldson, Alan; Stefansdottir, Vigdis; Barwell, Julian; James, Paul A; Murphy, Declan; Friedman, Eitan; Nicolai, Nicola; Greenhalgh, Lynn; Obeid, Elias; Murthy, Vedang; Copakova, Lucia; McGrath, John; Teo, Soo-Hwang; Strom, Sara; Kast, Karin; Leongamornlert, Daniel A; Chamberlain, Anthony; Pope, Jenny; Newlin, Anna C; Aaronson, Neil; Ardern-Jones, Audrey; Bangma, Chris; Castro, Elena; Dearnaley, David; Eyfjord, Jorunn; Falconer, Alison; Foster, Christopher S; Gronberg, Henrik; Hamdy, Freddie C; Johannsson, Oskar; Khoo, Vincent; Lubinski, Jan; Grindedal, Eli Marie; McKinley, Joanne; Shackleton, Kylie; Mitra, Anita V; Moynihan, Clare; Rennert, Gad; Suri, Mohnish; Tricker, Karen; Moss, Sue; Kote-Jarai, Zsofia; Vickers, Andrew; Lilja, Hans; Helfand, Brian T; Eeles, Rosalind A

    2018-01-01

    Background: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. Methods: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. Results: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml−l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. Conclusions: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone. PMID:29301143

  3. Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

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    Rong-hua Song

    2017-01-01

    Full Text Available As there are no previous studies on the interleukin-22 (IL-22 variants in autoimmune thyroid disease (AITD, the present study aimed to explore the association between polymorphisms of IL-22 and the predisposition to AITD. The study had 975 AITD patients, including 639 Graves’ disease (GD and 336 Hashimoto’s thyroiditis (HT individuals and 851 healthy cohorts. Ligase detection reaction (LDR and direct sequencing method were used for genotyping the IL-22 gene polymorphisms at rs2046068, rs2227478, rs2227485, rs11611206, and rs1179251. In comparison to female controls, genotype CC of rs1179251 was increased in the female AITD patients. Alleles C at rs2046068, C at rs2227478, and C at rs1179251 linked to the susceptibility of HT males. Genotype CC in rs1179251 was higher in male HT. Variants at rs2046068, rs2227478, and rs1179251 were associated with the AITD teenagers. Besides, genotype GG in rs11611206 was correlated with thyroid-associated ophthalmopathy (TAO. Moreover, allele G at rs11611206 was associated with decreased risk for TAO by 28.9%. Similarly, genotype CC of rs1179251 and genotype GG of rs11611206 were associated with Graves’ ophthalmopathy (GO. Allele G in rs11611206 increased people with HT towards the predisposition of hypothyroidism. In conclusion, genetic variants of IL-22 are associated with the occurrence of AITD.

  4. Determinatıon of Some Genetic Parameters, Phenotypic, Genetic and Environmental Trends and Environmental Factors Affecting Milk Yield Traits of Brown Swiss Cattle

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    Muhammet Hanifi Selvi

    2016-01-01

    Full Text Available In this study, genetic parameters, macro environmental factors and genetic, phenotypic and environmental trends for actual and 305 day milk yield of Brown Swiss cattle reared in Research Farm of Agricultural College at Atatürk University were estimated. Estimated breeding values that were used for calculation of the genetic trend and genetic parameters were estimated by using MTDFREML computer package program. Environmental factors affecting on actual and 305day milk yields were analysed by using Harvey statistic package program. While effects of the years and parities on the actual and 305-day milk yields were highly significant, the influence of the calving season was found to be insignificant. Environmental and phenotypic trends for actual and 305-day milk yields were determined as -33.2 kg and -29.0 kg; and -27.8±19.1 kg/year and -25.9±8.7 kg/year respectively. Genetic trends for actual and 305-day milk yields were calculated as 5.4±3.8 kg and 3.1±3.4 kg. Heritability’s for actual and 305-day milk yields were 0.21±0.12 and 0.16±0.14 respectively. Repeatability values for actual and 305-day milk yield were found as 0.29 and 0.33 respectively.

  5. Genetic predictors of obesity development

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    Svetlana V. Borodina

    2016-05-01

    Full Text Available The most common reasons that cause obesity are eating disorders (overeating, genetic predisposition, sedentary lifestyle (lack of exercise, disorders of the endocrine system, and environmental factors. There is evidence of an obvious relationship of high consumption of sugary drinks and weight gain. Since 1990, there has been considerable growth in the number of obese people in the first place associated with the promotion of soft drinks. According to a study in Finnish diabetes prevention average physical activity and change of diet (1200-1800 kcal of total fat intake with less than 30% saturated fat, including less than 10%, leading to long-term loss of excess weight (within 4 years. Many studies have demonstrated the impossibility of a single template approach to the determination of optimal diets for patients with overweight and obesity which has been shown in various studies on gene polymorphisms are associated with obesity, and their interaction. This article provides an overview of current data on the genetics of obesity covering the main provisions of the study of candidate genes, such as PPARG, FABP2, ADRB 2, ADRB3. The role nutrigenetics in the creation of individual programs of weight control and weight loss. But the question of the direct role of genetic factors in the development of obesity remains controversial, since one can not ignore the impact of environmental factors, such as lifestyle, diet, physical activity, stress, and harmful habits. To understand the mechanism of the relationship between genetic factors, environmental factors, and obesity, one needs to carry out research not only on the population level, but also in certain groups of people (ethnic, racial, age.

  6. The Genetic and Environmental Factors for Keratoconus

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    Ariela Gordon-Shaag

    2015-01-01

    Full Text Available Keratoconus (KC is the most common cornea ectatic disorder. It is characterized by a cone-shaped thin cornea leading to myopia, irregular astigmatism, and vision impairment. It affects all ethnic groups and both genders. Both environmental and genetic factors may contribute to its pathogenesis. This review is to summarize the current research development in KC epidemiology and genetic etiology. Environmental factors include but are not limited to eye rubbing, atopy, sun exposure, and geography. Genetic discoveries have been reviewed with evidence from family-based linkage analysis and fine mapping in linkage region, genome-wide association studies, and candidate genes analyses. A number of genes have been discovered at a relatively rapid pace. The detailed molecular mechanism underlying KC pathogenesis will significantly advance our understanding of KC and promote the development of potential therapies.

  7. Familial Investigations of Childhood Cancer Predisposition

    Science.gov (United States)

    2018-01-03

    Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease

  8. Are Genetics and Environment Substitutes or Complements in Affecting Entrepreneurial Choice?

    DEFF Research Database (Denmark)

    Zunino, Diego

    Recent twin and adoption studies have shown that genes matter for entrepreneurial choice. This related study addresses how a genetic predisposition to entrepreneurship interacts with the (entrepreneurship friendliness of the) environment, using a dataset of Italian twins. In particular, we study ...... a role, and that a favorable environment to entrepreneurship selects those with higher predisposition rather than simply increasing the rate of self-employment....... whether the genetic effect is different across genders, based on the stylized fact that barriers to entrepreneurship entry are stronger for females than for males. Using regression analysis, the study confirms earlier findings showing substantial genetic effects. More interestingly, the study finds...

  9. Genetic predisposition to salt-sensitivity : a systematic review

    NARCIS (Netherlands)

    Beeks, Esther; Kessels, Alfons G H; Kroon, Abraham A; van der Klauw, Melanie M; de Leeuw, Peter W

    PURPOSE: To assess the role of genetic polymorphisms in salt sensitivity of blood pressure. DATA IDENTIFICATION: We conducted a systematic review by searching the Medline literature from March 1993 to June 2003. Each paper was scrutinized and data concerning study population, method of salt

  10. Impact of prenatal environmental stress on cortical development

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    Seiji eIshii

    2015-05-01

    Full Text Available Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and 3. interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders.

  11. Genetic and environmental sources of individual religiousness: the roles of individual personality traits and perceived environmental religiousness.

    Science.gov (United States)

    Kandler, Christian; Riemann, Rainer

    2013-07-01

    In the current study, we examined the genetic and environmental sources of the links between individual religiousness and individual personality traits, perceived parental religiousness, and perceived peer religiousness. Data from 870 individuals (incl. 394 twin pairs) were analyzed. Variance in individual religiousness was significantly influenced by genetic effects, environmental influences shared by twins reared together, and individual-specific environmental influences. Individual religiousness showed significant associations with age, sex, specific personality traits (e.g., agreeableness, openness to values), and perceived religiousness of important social interaction partners, such as parents, best friends, and spouses. The links to personality traits were relatively small and primarily genetically mediated. The associations between individual religiousness and parental religiousness were substantial and mediated by shared environmental effects. These links significantly decreased across age accompanying a significant decrease of shared environmental influences on individual religiousness. The correlations between individual religiousness and perceived religiousness of spouses and best friends were relatively moderate but increased with age. These associations were mediated by genetic as well as nonshared environmental sources accompanying an increase of nonshared environmental influences on individual religiousness with age. The results suggest that inter-individual differences in religiousness are due to multiple sources.

  12. Genetic and environmental sources of individual differences in views on aging.

    Science.gov (United States)

    Kornadt, Anna E; Kandler, Christian

    2017-06-01

    Views on aging are central psychosocial variables in the aging process, but knowledge about their determinants is still fragmental. Thus, the authors investigated the degree to which genetic and environmental factors contribute to individual differences in various domains of views on aging (wisdom, work, fitness, and family), and whether these variance components vary across ages. They analyzed data from 350 monozygotic and 322 dizygotic twin pairs from the Midlife Development in the U.S. (MIDUS) study, aged 25-74. Individual differences in views on aging were mainly due to individual-specific environmental and genetic effects. However, depending on the domain, genetic and environmental contributions to the variance differed. Furthermore, for some domains, variability was larger for older participants; this was attributable to increases in environmental components. This study extends research on genetic and environmental sources of psychosocial variables and stimulates future studies investigating the etiology of views on aging across the life span. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study

    Science.gov (United States)

    Padmanabhan, Sandosh; Porteous, David J.; Burri, Andrea V.; Tanaka, Haruka; Williams, Frances M. K.

    2017-01-01

    (OR 2·20 [1·90–2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05–1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63–2·95]), and depression, angina (OR 1·98 [1·49–2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99–4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05–9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85–12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, prelationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06–0·23]). Conclusion We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms. PMID:28225781

  14. Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study.

    Directory of Open Access Journals (Sweden)

    Oliver van Hecke

    ]. Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71], angina predicted chronic pain in the other (OR 2·19 [1·63-2·95], and depression, angina (OR 1·98 [1·49-2·65]. Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]; angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95] and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]. In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01. Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23].We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

  15. Dermatitis Herpetiformis: From the Genetics to the Development of Skin Lesions

    Directory of Open Access Journals (Sweden)

    Diletta Bonciani

    2012-01-01

    Full Text Available Dermatitis herpetiformis (DH is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD. Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.

  16. Genetic and Environmental Contributions to Covariation Between DHEA and Testosterone in Adolescent Twins.

    Science.gov (United States)

    Van Hulle, Carol A; Moore, Mollie N; Shirtcliff, Elizabeth A; Lemery-Chalfant, Kathryn; Goldsmith, H Hill

    2015-05-01

    Although several studies have shown that pubertal tempo and timing are shaped by genetic and environmental factors, few studies consider to what extent endocrine triggers of puberty are shaped by genetic and environmental factors. Doing so moves the field from examining correlated developmentally-sensitive biomarkers toward understanding what drives those associations. Two puberty related hormones, dehydroepiandrosterone and testosterone, were assayed from salivary samples in 118 MZ (62 % female), 111 same sex DZ (46 % female) and 103 opposite-sex DZ twin pairs, aged 12-16 years (M = 13.1, SD = 1.3). Pubertal status was assessed with a composite of mother- and self-reports. We used biometric models to estimate the genetic and environmental influences on the variance and covariance in testosterone and DHEA, with and without controlling for their association with puberty, and to test for sex differences. In males, the variance in testosterone and pubertal status was due to shared and non-shared environmental factors; variation in DHEA was due to genetic and non-shared environmental factors. In females, variance in testosterone was due to genetic and non-shared environmental factors; genetic, shared, and non-shared environmental factors contributed equally to variation in DHEA. In males, the testosterone-DHEA covariance was primarily due to shared environmental factors that overlapped with puberty as well as shared and non-shared environmental covariation specific to testosterone and DHEA. In females, the testosterone-DHEA covariance was due to genetic factors overlapping with pubertal status, and shared and non-shared environmental covariation specific to testosterone and DHEA.

  17. Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

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    Karin A W Wadt

    Full Text Available Both environmental and host factors influence risk of cutaneous melanoma (CM, and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.

  18. [Allergy - an environmental disease].

    Science.gov (United States)

    Traidl-Hoffmann, Claudia

    2017-06-01

    The increase in allergies is a phenomenon that is being observed in all fast-developing countries. For a long time, science has taken as a starting point that solely a genetic predisposition is a precondition for the development of an allergy. Today, knowledge of environmental factors that can alter genes or the transcription of genes in the cells, has improved. Epidemiological studies have meanwhile identified several environmental factors that have a protective or supporting effect on allergy development. The environmental microbiome has recently gained central interest. A common theme in most of the studies is diversity: reduced diversity is correlated with enhanced risk for chronic inflammatory diseases and allergy.It is now of great interest for research to further analyze such environment-gene and/or environment-human interactions on all levels - from organs to cells to small and microstructures such as genes. For immunologists, it is specifically about understanding the influencing factors and effector pathways of allergens, and to apply thereby obtained insights in the follow-up for the ultimate goal of allergy research - prevention.

  19. Genetic and environmental influences on focal brain density in bipolar disorder

    NARCIS (Netherlands)

    van der Schot, Astrid C.; Vonk, Ronald; Brouwer, Rachel M.; van Baal, G. Caroline M.; Brans, Rachel G. H.; van Haren, Neeltje E. M.; Schnack, Hugo G.; Boomsma, Dorret I.; Nolen, Willem A.; Pol, Hilleke E. Hulshoff; Kahn, Rene S.

    2010-01-01

    Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. To investigate the contribution of genetic and environmental factors on grey

  20. Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway

    Directory of Open Access Journals (Sweden)

    Giannoudis Peter V

    2011-02-01

    Full Text Available Abstract Background Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing. Methods A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP pathway (BMP-2, BMP-7, NOGGIN and SMAD6 were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs, and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA. Results Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year], and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6 to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age. Conclusions This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further

  1. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    Directory of Open Access Journals (Sweden)

    Elinor Sawyer

    2014-04-01

    Full Text Available Invasive lobular breast cancer (ILC accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+ and often associated with lobular carcinoma in situ (LCIS. Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI for ILC = 1.13 (1.09-1.18, P = 6.0 × 10(-10; P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4. Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03; and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04. In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365 and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7. In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity

  2. Genetic parameters, phenotypic, genotypic and environmental correlations and genetic variability on sunflower in the Brazilian Savannah

    Directory of Open Access Journals (Sweden)

    Ellen Grippi Lira

    Full Text Available ABSTRACT: Sunflower (Helianthus annuus L. is an annual crop that stands out for its production of high quality oil and for an efficient selection, being necessary to estimate the components of genetic and phenotypic variance. This study aimed to estimate genetic parameters, phenotypic, genotypic and environmental correlations and genetic variability on sunflower in the Brazilian Savannah, evaluating the characters grain yield (YIELD, days to start flowering (DFL based on flowering date in R5, chapter length (CL, weight of a thousand achenes (WTA, plant height (H and oil content (OilC of 16 sunflower genotypes. The experiment was conducted at Embrapa Cerrados, Planaltina, DF, situated at 15º 35’ 30”S latitude, 47º 42’ 30”W longitude and 1.007m above sea level, in soil classified as dystroferric Oxisol. The experimental design used was a complete randomized block with four replicates. The nature for the effects of genotypes and blocks was fixed. Except for the character chapter length, genetic variance was the main component of the phenotypic variance among the genotypes, indicating high genetic variability and experimental efficiency with proper environmental control. In absolute terms, the genetic correlations were superior to phenotypic and environmental. The high values reported for heritability and selective accuracy indicated efficiency of phenotypic selection. Results showed high genetic variability among genotypes, which may contribute to the genetic improvement of sunflower.

  3. Genetic and environmental transmission of body mass index fluctuation.

    Science.gov (United States)

    Bergin, Jocilyn E; Neale, Michael C; Eaves, Lindon J; Martin, Nicholas G; Heath, Andrew C; Maes, Hermine H

    2012-11-01

    This study sought to determine the relationship between body mass index (BMI) fluctuation and cardiovascular disease phenotypes, diabetes, and depression and the role of genetic and environmental factors in individual differences in BMI fluctuation using the extended twin-family model (ETFM). This study included 14,763 twins and their relatives. Health and Lifestyle Questionnaires were obtained from 28,492 individuals from the Virginia 30,000 dataset including twins, parents, siblings, spouses, and children of twins. Self-report cardiovascular disease, diabetes, and depression data were available. From self-reported height and weight, BMI fluctuation was calculated as the difference between highest and lowest BMI after age 18, for individuals 18-80 years. Logistic regression analyses were used to determine the relationship between BMI fluctuation and disease status. The ETFM was used to estimate the significance and contribution of genetic and environmental factors, cultural transmission, and assortative mating components to BMI fluctuation, while controlling for age. We tested sex differences in additive and dominant genetic effects, parental, non-parental, twin, and unique environmental effects. BMI fluctuation was highly associated with disease status, independent of BMI. Genetic effects accounted for ~34 % of variance in BMI fluctuation in males and ~43 % of variance in females. The majority of the variance was accounted for by environmental factors, about a third of which were shared among twins. Assortative mating, and cultural transmission accounted for only a small proportion of variance in this phenotype. Since there are substantial health risks associated with BMI fluctuation and environmental components of BMI fluctuation account for over 60 % of variance in males and over 50 % of variance in females, environmental risk factors may be appropriate targets to reduce BMI fluctuation.

  4. Can exposure to environmental chemicals increase the risk of diabetes type 1 development?

    Science.gov (United States)

    Bodin, Johanna; Stene, Lars Christian; Nygaard, Unni Cecilie

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

  5. Can Exposure to Environmental Chemicals Increase the Risk of Diabetes Type 1 Development?

    Directory of Open Access Journals (Sweden)

    Johanna Bodin

    2015-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

  6. Peripartum Cardiomyopathy: Moving Towards a More Central Role of Genetics#

    Science.gov (United States)

    Cemin, Roberto; Janardhanan, Rajesh; Donazzan, Luca; Daves, Massimo

    2013-01-01

    Peripartum cardiomyopathy (PCM) is a relatively rare disease with potentially devasting consequences requiring prompt identification and correct treatment. Overall prognosis is good in majority of the cases, although some patients may progress to irreversible heart failure. Early diagnosis is important and effective treatment reduces mortality rates and increases the chance of complete recovery of ventricular systolic function. The aetiology and pathogenesis seems to be multifactorial and poorly understood, with the available literature rather conflicting. In recent years, there has been increased interest in the role played by genetic predisposition in the development of PCM. It probably develops as a result of a complex interaction of pregnancy-associated factors and genetic factors and recently there have been many observations pointing out the central role played by a genetic predisposition. The direct and indirect observations on genetic susceptibility may offer new insights into the pathogenesis of PCM. However, larger studies are needed before advising routine genetic testing in these patients. PMID:23909634

  7. Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome

    OpenAIRE

    Ussar, Siegfried; Griffin, Nicholas W.; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I.; Kahn, C. Ronald

    2015-01-01

    Obesity, diabetes and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly-used inbred strains of mice – obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ, from Jackson Laboratory and obesity-prone, but diabetes resistant 129S6/SvEvTac from Taconic - plus three derivative lines generated by breeding these strains in a new, common environm...

  8. Immunology and Genetic of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Norma C. Serrano

    2006-01-01

    Full Text Available Preeclampsia is a disease characterized by hypertension and proteinuria in the third trimester of pregnancy. Preeclampsia is a major cause of maternal mortality, and fetal death, especially in developing countries, but its aetiology remains unclear. Key findings support a causal role of superficial placentation driven by immune mal maladaptation, which then lead to reduced concentrations of angiogenic growth factors and to an increase in placental debris in the maternal circulation resulting in a maternal inflammatory response. Epidemiological research has consistently demonstrated a substantial familial predisposition to preeclampsia. Unfortunately, the conquest of the genes explaining such a individual susceptibility has been proved to be a hard task. However, genetics will also inform us about causality of environmental factors, and then serve as a tool to prioritize therapeutic targets for preventive strategies.

  9. [Genetic predisposition to breast and ovarian cancer: importance of test results].

    Science.gov (United States)

    Julian-Reynier, Claire

    2011-01-01

    Oncogenetic consultations and predictive BRCA1/2 testing are intertwined processes and the specific impact of these genetic tests if performed alone through direct-to-consumer offers remains unknown. Noteworthy, the expectations of patients vary with their own status, whether they are affected or not by breast cancer at the time genetic testing is performed. The prescription of genetic tests for BCRA mutations has doubled in France between 2003 and 2009. There is a consensus on the fact that genetic results disclosure led to a significant increase in the knowledge and understanding that the patients have of the genetic risk and also changed the medical follow-up of these patients. Evaluating the psychological burden of tests disclosure did not reveal any major distress in patients who are followed by high-quality multidisciplinary teams. Longitudinal cohorts studies have now evaluated the perception and behaviour of these patients, and observed sociodemographic as well as geographic and psychosocial differences both in the acceptation of prophylactic strategies such as surgery, and time to surgery. © 2011 médecine/sciences - Inserm / SRMS.

  10. Autoimmunity, environmental exposure and vaccination: is there a link?

    International Nuclear Information System (INIS)

    Ravel, G.; Christ, M.; Horand, F.; Descotes, J.

    2004-01-01

    Although the wide clinical experience shows that vaccines are generally safe, concern has been expressed for a causal link between vaccines and autoimmune diseases. Even though the mechanisms of autoimmunity are ill-elucidated, the role of pre-existing risk factors including genetic predisposition and environmental factors is largely accepted. The present study was undertaken to test the hypothesis that vaccines can promote autoimmunity in genetically-prone individuals when simultaneously exposed to a chemical known to induce autoimmune reactions. Female lupus-prone (NZBxNZW) F 1 mice were given 1 μg or 10 μg of a hepatitis B vaccine at 2-week intervals in conjunction with 40 μg of mercuric chloride three times per week for 6 weeks. A marked increase in serum IgG levels and a slight increase in anti-nuclear autoantibody (ANA) levels were seen in the mice given 10 μg of the vaccine plus mercuric chloride. No straightforward conclusion can be drawn from these results because of the extreme experimental conditions of this study. Nevertheless, the results tend to support the hypothesis that vaccination could enhance the risk of autoimmunity in genetically susceptible individuals when exposed to certain environmental chemicals

  11. Methodological issues of genetic association studies.

    Science.gov (United States)

    Simundic, Ana-Maria

    2010-12-01

    Genetic association studies explore the association between genetic polymorphisms and a certain trait, disease or predisposition to disease. It has long been acknowledged that many genetic association studies fail to replicate their initial positive findings. This raises concern about the methodological quality of these reports. Case-control genetic association studies often suffer from various methodological flaws in study design and data analysis, and are often reported poorly. Flawed methodology and poor reporting leads to distorted results and incorrect conclusions. Many journals have adopted guidelines for reporting genetic association studies. In this review, some major methodological determinants of genetic association studies will be discussed.

  12. Generalizing genetical genomics : getting added value from environmental perturbation

    NARCIS (Netherlands)

    Li, Yang; Breitling, Rainer; Jansen, Ritsert C.

    2008-01-01

    Genetical genomics is a useful approach for studying the effect of genetic perturbations on biological systems at the molecular level. However, molecular networks depend on the environmental conditions and, thus, a comprehensive understanding of biological systems requires studying them across

  13. Genetic and Environmental Influences on Retinopathy of Prematurity

    Science.gov (United States)

    Ortega-Molina, J. M.; Anaya-Alaminos, R.; Uberos-Fernández, J.; Solans-Pérez de Larraya, A.; Chaves-Samaniego, M. J.; Salgado-Miranda, A.; Piñar-Molina, R.; Jerez-Calero, A.; García-Serrano, J. L.

    2015-01-01

    Objective. The goals were to isolate and study the genetic susceptibility to retinopathy of prematurity (ROP), as well as the gene-environment interaction established in this disease. Methods. A retrospective study (2000–2014) was performed about the heritability of retinopathy of prematurity in 257 infants who were born at a gestational age of ≤32 weeks. The ROP was studied and treated by a single pediatric ophthalmologist. A binary logistic regression analysis was completed between the presence or absence of ROP and the predictor variables. Results. Data obtained from 38 monozygotic twins, 66 dizygotic twins, and 153 of simple birth were analyzed. The clinical features of the cohorts of monozygotic and dizygotic twins were not significantly different. Genetic factors represented 72.8% of the variability in the stage of ROP, environmental factors 23.08%, and random factors 4.12%. The environmental variables representing the highest risk of ROP were the number of days of tracheal intubation (p < 0.001), postnatal weight gain (p = 0.001), and development of sepsis (p = 0.0014). Conclusion. The heritability of ROP was found to be 0.73. The environmental factors regulate and modify the expression of the genetic code. PMID:26089603

  14. Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Cameron M Scott

    Full Text Available DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.

  15. Verification of the model of predisposition in triathlon – structural model of confirmative factor analysis

    Directory of Open Access Journals (Sweden)

    Lenka Kovářová

    2012-09-01

    Full Text Available BACKGROUND: The triathlon is a combination of three different types of sport – swimming, cycling, and running. Each of these requires different top level predispositions and complex approach to talent selection is a rather difficult process. Attempts to identify assumptions in the triathlon have so far been specific and focused only on some groups of predispositions (physiology, motor tests, and psychology. The latest studies missed the structural approach and were based on determinants of sport performance, theory of sports training and expert assessment. OBJECTIVE: The aim of our study was to verify the model of predisposition in the short triathlon for talent assessment of young male athletes age 17–20 years. METHODS: The research sample consisted of 55 top level triathletes – men, who were included in the Government supported sports talent programme in the Czech Republic at the age of 17–20 years. We used a confirmative factor analysis (FA and Path diagram to verify the model, which allow us to explain mutual relationships among observed variables. For statistical data processing we used a structure equating modeling (SEM by software Lisrel L88. RESULTS: The study confirms best structural model for talent selection in triathlon at the age of 17–20 years old men, which composed seventeen indicators (tests and explained 91% of all cross-correlations (Goodness of Fit Index /GFI/ 0.91, Root Mean Square Residual /RMSR/ 0.13. Tests for predispositions in triathlons were grouped into five items, three motor predispositions (swimming, cycling and running skills, aerobic and psychological predispositions. Aerobic predispositions showed the highest importance to the assumptions to the general factor (1.00; 0. Running predispositions were measured as a very significant factor (–0.85; 0.28 which confirms importance of this critical stage of the race. Lower factor weight showed clusters of swimming (–0.61; 0.63 and cycling (0.53; 0

  16. Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

    DEFF Research Database (Denmark)

    Drost, Mark; Lützen, Anne; van Hees, Sandrine

    2013-01-01

    In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... function. When a residue identified as mutated in an individual suspected of Lynch syndrome is listed as critical in such a reverse diagnosis catalog, there is a high probability that the corresponding human VUS is pathogenic. To investigate the applicability of this approach, we have generated....... Nearly half of these critical residues match with VUS previously identified in individuals suspected of Lynch syndrome. This aids in the assignment of pathogenicity to these human VUS and validates the approach described here as a diagnostic tool. In a wider perspective, this work provides a model...

  17. Environmental enrichment ameliorates depressive-like symptoms in young rats bred for learned helplessness.

    Science.gov (United States)

    Richter, S Helene; Zeuch, Benjamin; Riva, Marco A; Gass, Peter; Vollmayr, Barbara

    2013-09-01

    The incidence of major depression is known to be influenced by both genetic and environmental factors. In the current study, we therefore set out to investigate depressive-like behavior and its modification by environmental enrichment using rats bred for 'learned helplessness'. 45 males of congenitally helpless (cLH, n=22) and non-helpless (cNLH, n=23) rats of two different generations were used to systematically investigate differential effects of environmental enrichment on learned helpless behavior, anhedonic-like behavior (sweetened condensed milk consumption) and spontaneous behavior in the home cage. While enrichment was found to reduce learned helpless behavior in 14 weeks old, but not 28 weeks old cLH rats, it did not affect the consumption of sweetened condensed milk. Regarding the home cage behavior, no consistent changes between rats of different strains, housing conditions, and ages were observed. We could thus demonstrate that a genetic predisposition for learned helplessness may interact with environmental conditions in mediating some, but not all depressive-like symptoms in congenitally learned helpless rats. However, future efforts are needed to isolate the differential benefits of environmental factors in mediating the different depression-related symptoms. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Geoepidemiology, Genetic and Environmental Risk Factors for PBC.

    Science.gov (United States)

    Zhang, Haiyan; Carbone, Marco; Lleo, Ana; Invernizzi, Pietro

    2015-01-01

    Primary biliary cirrhosis (PBC) is the most paradigmatic autoimmune liver disease with still several controversial issues in epidemiology, diagnosis, causation, and therapy. Although we are witnessing an enormous increase in the quantum of our basic knowledge of the disease with an initial translation in clinical practice, there are still a number of key open questions in PBC. Among them are the following questions: Why are there vast geographical variations in disease frequency? What are the reasons for female preponderance? Why do only small-size bile ducts get affected: What is the real role of genetics and epigenetics in its development? In particular, the prevalence of PBC is known to vary both on an international and a regional level, suggesting the existence of substantive geographical differences in terms of genetic susceptibility and environmental factors. New theories on potential environmental triggers, such as chemical xenobiotics, which lead to the breaking of self-tolerance within a unique immunological milieu of the liver, have been suggested. On the other hand, new and solid data on the genetic architecture of PBC are now obtained from recent high-throughput studies, together with data on sex chromosomes defects, and epigenetic abnormalities, thus strongly suggesting a role of genetic and epigenetic factors in the triggering and perpetuation of the autoimmune aggression in PBC. Based on these evidences, a number of novel drugs directed against specific immune-related molecules are currently under development. In this paper, we review a comprehensive collection of current epidemiological reports from various world regions. We also discuss here the most recent data regarding candidate genetic and environmental risk factors for PBC. © 2015 S. Karger AG, Basel.

  19. Spectrum and prevalence of genetic predisposition in medulloblastoma

    DEFF Research Database (Denmark)

    Waszak, Sebastian M; Northcott, Paul A; Buchhalter, Ivo

    2018-01-01

    Research; German Cancer Research Center; St Jude Comprehensive Cancer Center; American Lebanese Syrian Associated Charities; Swiss National Science Foundation; European Molecular Biology Organization; Cancer Research UK; Hertie Foundation; Alexander and Margaret Stewart Trust; V Foundation for Cancer...... and the Clark H Smith Brain Tumour Centre; Montreal Children's Hospital Foundation; The Hospital for Sick Children: Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, MDT's Garron Family Endowment; BC Childhood Cancer Parents...

  20. Prediction of breeding values and selection responses with genetic heterogeneity of environmental variance

    NARCIS (Netherlands)

    Mulder, H.A.; Bijma, P.; Hill, W.G.

    2007-01-01

    There is empirical evidence that genotypes differ not only in mean, but also in environmental variance of the traits they affect. Genetic heterogeneity of environmental variance may indicate genetic differences in environmental sensitivity. The aim of this study was to develop a general framework

  1. Musical predispositions in infancy.

    Science.gov (United States)

    Trehub, S E

    2001-06-01

    Some scholars consider music to exemplify the classic criteria for a complex human adaptation, including universality, orderlying development, and special-purpose cortical processes. The present account focuses on processing predispositions for music. The early appearance of receptive musical skills, well before they have obvious utility, is consistent with their proposed status as predispositions. Infants' processing of musical or music-like patterns is much like that of adults. In the early months of life, infants engage in relational processing of pitch and temporal patterns. They recognize a melody when its pitch level is shifted upward or downward, provided the relations between tones are preserved. They also recognize a tone sequence when the tempo is altered so long as the relative durations remain unchanged. Melodic contour seems to be the most salient feature of melodies for infant listeners. However, infants can detect interval changes when the component tones are related by small-integer frequency ratios. They also show enhanced processing for scales with unequal steps and for metric rhythms. Mothers sing regularly to infants, doing so in a distinctive manner marked by high pitch, slow tempo, and emotional expressiveness. The pitch and tempo of mothers' songs are unusually stable over extended periods. Infant listeners prefer the maternal singing style to the usual style of singing, and they are more attentive to maternal singing than to maternal speech. Maternal singing also has a moderating effect on infant arousal. The implications of these findings for the origins of music are discussed.

  2. Model comparisons and genetic and environmental parameter ...

    African Journals Online (AJOL)

    arc

    Model comparisons and genetic and environmental parameter estimates of growth and the ... breeding strategies and for accurate breeding value estimation. The objectives ...... Sci. 23, 72-76. Van Wyk, J.B., Fair, M.D. & Cloete, S.W.P., 2003.

  3. HSP90 Shapes the Consequences of Human Genetic Variation.

    Science.gov (United States)

    Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

    2017-02-23

    HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Genetic Determinants of Macrovascular Complications and Mortality in Type 2 Diabetes

    NARCIS (Netherlands)

    M. Yazdanpanah (Mojgan)

    2006-01-01

    textabstractEvidence is accumulating that there is a genetic predisposition for the development of vascular complications of type 2 diabetes. There is a large variation in the risk and onset of complication in patients, which may partly be explained by genetic susceptibility. Most likely

  5. Genetic and environmental trends of early growth traits in the ...

    African Journals Online (AJOL)

    Data from the Elsenburg Dormer sheep stud were used to estimate genetic and environmental change in early growth traits from 1943 to 1990. .... The Elsenburg stud is not only the foundation Dormer stud, ... derivative-free algorithm. Genet.

  6. Overlapping genetic and child-specific nonshared environmental influences on listening comprehension, reading motivation, and reading comprehension.

    Science.gov (United States)

    Schenker, Victoria J; Petrill, Stephen A

    2015-01-01

    This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Overlapping Genetic and Child-Specific Nonshared Environmental Influences on Listening Comprehension, Reading Motivation, and Reading Comprehension

    Science.gov (United States)

    Schenker, Victoria J.; Petrill, Stephen A.

    2015-01-01

    This study investigated the genetic and environmental influences on observed associations between listening comprehension, reading motivation, and reading comprehension. Univariate and multivariate quantitative genetic models were conducted in a sample of 284 pairs of twins at a mean age of 9.81 years. Genetic and nonshared environmental factors accounted for statistically significant variance in listening and reading comprehension, and nonshared environmental factors accounted for variance in reading motivation. Furthermore, listening comprehension demonstrated unique genetic and nonshared environmental influences but also had overlapping genetic influences with reading comprehension. Reading motivation and reading comprehension each had unique and overlapping nonshared environmental contributions. Therefore, listening comprehension appears to be related to reading primarily due to genetic factors whereas motivation appears to affect reading via child-specific, nonshared environmental effects. PMID:26321677

  8. Genetic and Environmental Influences on Global Family Conflict

    Science.gov (United States)

    Horwitz, Briana N.; Neiderhiser, Jenae M.; Ganiban, Jody M.; Spotts, Erica L.; Lichtenstein, Paul; Reiss, David

    2010-01-01

    This study examined genetic and environmental influences on global family conflict. The sample comprised 872 same-sex pairs of twin parents, their spouses/partners and one adolescent child per twin from the Twin and Offspring Study in Sweden (TOSS). The twins, spouses and child each reported on the degree of family conflict, and there was significant agreement among the family members’ ratings. These shared perspectives were explained by one common factor, indexing global family conflict. Genetic influences explained 36% of the variance in this common factor, suggesting that twins’ heritable characteristics contribute to family conflict, via genotype-environment correlation. Nonshared environmental effects explained the remaining 64% of this variance, indicating that twins’ unique childhood and/or current family experiences also play an important role. PMID:20438198

  9. Familial predisposition to vasovagal syncope.

    Science.gov (United States)

    Negrusz-Kawecka, Marta; Bańkowski, Tomasz; Tabin, Mateusz; Paprocka, Magdalena; Mercik, Agnieszka; Misztal, Jowita; Nowak, Piotr; Zysko, Dorota; Gajek, Jacek

    2012-06-01

    A handful of studies suggest a familial predisposition to vasovagal syncope (WS) but the scope of information available to date is poor. The aim of our study was to evaluate the prevalence of vasovagal syncope and its familial occurrence in the young. The studied group consisted of 281 women and 111 men, aged 18-32 years. Forty-seven percent of the population had one brother or sister, and the mean number of individuals per family was 4.4 +/- 1.0. The questionnaire consisted of 30 questions regarding syncopal history. Syncope was reported in 32.1% of the patients studied (36.7% in women vs. 20.7% in men; P < 0.05), 29.1% of mothers, 16.8% of fathers, 30.9% of sisters and 14.2% of brothers. Logistic regression analysis revealed that positive history regarding the syncope in the whole group of students was related to the female gender (OR 2.17; CI: 1.28-3.7), the history of a syncope in mother (OR 1.74; CI: 1.09-2.78) and the history of a syncope in father (OR 2.22; CI: 1.28-3.86; P < 0.001). A positive history of syncope in male relatives increases the risk of syncope in men and women, whereas a positive history of syncope in female relatives increases the risk of syncope in women only. Female gender independently of the family history increases the risk of syncope. The genetics of the vasovagal syncope could be polygenic but the mechanisms of a transmission remain unclear to date.

  10. Monitoring adaptive genetic responses to environmental change

    DEFF Research Database (Denmark)

    Hansen, M.M.; Olivieri, I.; Waller, D.M.

    2012-01-01

    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how...... for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We...

  11. Genetic and environmental variance in content dimensions of the MMPI.

    Science.gov (United States)

    Rose, R J

    1988-08-01

    To evaluate genetic and environmental variance in the Minnesota Multiphasic Personality Inventory (MMPI), I studied nine factor scales identified in the first item factor analysis of normal adult MMPIs in a sample of 820 adolescent and young adult co-twins. Conventional twin comparisons documented heritable variance in six of the nine MMPI factors (Neuroticism, Psychoticism, Extraversion, Somatic Complaints, Inadequacy, and Cynicism), whereas significant influence from shared environmental experience was found for four factors (Masculinity versus Femininity, Extraversion, Religious Orthodoxy, and Intellectual Interests). Genetic variance in the nine factors was more evident in results from twin sisters than those of twin brothers, and a developmental-genetic analysis, using hierarchical multiple regressions of double-entry matrixes of the twins' raw data, revealed that in four MMPI factor scales, genetic effects were significantly modulated by age or gender or their interaction during the developmental period from early adolescence to early adulthood.

  12. Association study of functional genetic variants of innate immunity related genes in celiac disease

    Directory of Open Access Journals (Sweden)

    Martín J

    2005-08-01

    Full Text Available Abstract Background Recent evidence suggest that the innate immune system is implicated in the early events of celiac disease (CD pathogenesis. In this work for the first time we have assessed the relevance of different proinflammatory mediators typically related to innate immunity in CD predisposition. Methods We performed a familial study in which 105 celiac families characterized by the presence of an affected child with CD were genotyped for functional polymorphisms located at regulatory regions of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes. Familial data was analysed with a transmission disequilibrium test (TDT that revealed no statistically significant differences in the transmission pattern of the different genetic markers considered. Results The TDT analysis for IL-1α, IL-1β, IL-1RN, IL-18, and MCP-1 genes genetic variants did not reveal biased transmission to the affected offspring. Only a borderline association of RANTES promoter genetic variants with CD predisposition was observed. Conclusion Our results suggest that the analysed polymorphisms of IL-1α, IL-1β, IL-1RN, IL-18, RANTES and MCP-1 genes do not seem to play a major role in CD genetic predisposition in our population.

  13. Genetic and environmental influences on motor function: a magnetoencephalographic study of twins

    Directory of Open Access Journals (Sweden)

    Toshihiko eAraki

    2014-06-01

    Full Text Available To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities of movement-related cortical fields (MRCFs in middle-aged and elderly monozygotic (MZ twins. MRCFs were measured using a 160-channel MEG system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1 between 16 MZ twins and 16 pairs of genetically unrelated pairs. Differences in latency and dipole location between MZ twins were significantly less than those between unrelated age-matched pairs. However, amplitude and dipole intensity were not significantly different. These results suggest that the latency and dipole location of MEF1 are determined early in life by genetic and early common environmental factors, whereas amplitude and dipole intensity are influenced by long-term environmental factors. Improved understanding of genetic and environmental factors that influence cerebral motor function may contribute to evaluation and improvement for individual motor function.

  14. Innate and adaptive immune traits are differentially affected by genetic and environmental factors

    Science.gov (United States)

    Mangino, Massimo; Roederer, Mario; Beddall, Margaret H.; Nestle, Frank O.; Spector, Tim D.

    2017-01-01

    The diversity and activity of leukocytes is controlled by genetic and environmental influences to maintain balanced immune responses. However, the relative contribution of environmental compared with genetic factors that affect variations in immune traits is unknown. Here we analyse 23,394 immune phenotypes in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4+ T and CD8+ T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment. PMID:28054551

  15. The development of an online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making: a usability and pilot study.

    Science.gov (United States)

    Reumkens, Kelly; Tummers, Marly H E; Gietel-Habets, Joyce J G; van Kuijk, Sander M J; Aalfs, Cora M; van Asperen, Christi J; Ausems, Margreet G E M; Collée, Margriet; Dommering, Charlotte J; Kets, C Marleen; van der Kolk, Lizet E; Oosterwijk, Jan C; Tjan-Heijnen, Vivianne C G; van der Weijden, Trudy; de Die-Smulders, Christine E M; van Osch, Liesbeth A D M

    2018-05-30

    An online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final decision aid was pilot tested (N = 16) with paired sample t tests comparing main outcomes (decisional conflict, knowledge, realistic expectations regarding the reproductive options and decision self-efficacy) before (T0), immediately (T1) and 2 weeks after (T2) use of the decision aid. Pilot testing indicated decreased decisional conflict scores, increased knowledge, and improved realistic expectations regarding the reproductive options, at T1 and T2. No effect was found for couples' decision self-efficacy. The positive findings during usability testing were thus reflected in the pilot study. The decision aid will be further evaluated in a nationwide pretest-posttest study to facilitate implementation in the onco-genetic counselling setting. Ultimately, it is expected that the decision aid will enable end-users to make an informed decision.

  16. Molecular and genetic mechanisms of environmental mutagens

    International Nuclear Information System (INIS)

    Kubitschek, H.E.; Derstine, P.L.; Griego, V.M.; Matsushita, T.; Peak, J.G.; Peak, M.J.; Reynolds, P.R.; Webb, R.B.; Williams-Hill, D.

    1981-01-01

    This program is primarily concerned with elucidation of the nature of DNA lesions produced by environmental and energy related mutagens, their mechanisms of action, and their repair. The main focus is on actions of chemical mutagens and electromagnetic radiations. Synergistic interactions between mutagens and the mutational processes that lead to synergism are being investigated. Mutagens are chosen for study on the basis of their potential for analysis of mutation (as genetic probes), for development of procedures for reducing mutational damage, for their potential importance to risk assessment, and for development of improved mutagen testing systems. Bacterial cells are used because of the rapidity and clarity of scientific results that can be obtained, the detailed genetic maps, and the many well-defined mutand strains available. The conventional tools of microbial and molecular genetics are used, along with intercomparison of genetically related strains. Advantage is taken of tcollective dose commitment will result in more attention being paid to potential releases of radionuclides at relatively short times after disposal

  17. The genetics of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Silverman Edwin K

    2001-01-01

    Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is a significant cause of global morbidity and mortality. Previous studies have shown that COPD aggregates in families, suggesting a genetic predisposition to airflow obstruction. Many candidate genes have been assessed, but the data are often conflicting. We review the genetic factors that predispose smokers to COPD and highlight the future role of genomic scans in identifying novel susceptibility genes.

  18. Environmental heterogeneity explains the genetic structure of Continental and Mediterranean populations of Fraxinus angustifolia Vahl.

    Directory of Open Access Journals (Sweden)

    Martina Temunović

    Full Text Available Tree species with wide distributions often exhibit different levels of genetic structuring correlated to their environment. However, understanding how environmental heterogeneity influences genetic variation is difficult because the effects of gene flow, drift and selection are confounded. We investigated the genetic variation and its ecological correlates in a wind-pollinated Mediterranean tree species, Fraxinus angustifolia Vahl, within a recognised glacial refugium in Croatia. We sampled 11 populations from environmentally divergent habitats within the Continental and Mediterranean biogeographical regions. We combined genetic data analyses based on nuclear microsatellite loci, multivariate statistics on environmental data and ecological niche modelling (ENM. We identified a geographic structure with a high genetic diversity and low differentiation in the Continental region, which contrasted with the significantly lower genetic diversity and higher population divergence in the Mediterranean region. The positive and significant correlation between environmental and genetic distances after controlling for geographic distance suggests an important influence of ecological divergence of the sites in shaping genetic variation. The ENM provided support for niche differentiation between the populations from the Continental and Mediterranean regions, suggesting that contemporary populations may represent two divergent ecotypes. Ecotype differentiation was also supported by multivariate environmental and genetic distance analyses. Our results suggest that despite extensive gene flow in continental areas, long-term stability of heterogeneous environments have likely promoted genetic divergence of ashes in this region and can explain the present-day genetic variation patterns of these ancient populations.

  19. Environmental impact assessment of genetically modified biocontrol agents

    International Nuclear Information System (INIS)

    Migheli, Q.

    2001-01-01

    This review summarises the theoretical basis of risk analysis, and the political and social implications of introducing new biotechnology products in agricultural environments. The main factors to be considered under the present European regulation in the environmental impact assessment of genetically modified biocontrol agents are briefly discussed. Finally, an alternative risk assessment paradigm is proposed for genetically modified microorganisms, which shall consider the intrinsic properties of each antagonist, rather than the method used for generating it [it

  20. Twin Studies in Autism: What Might They Say about Genetic and Environmental Influences

    Science.gov (United States)

    Anderson, George M.

    2012-01-01

    Genetic and epigenetic differences exist within monozygote twin-pairs and might be especially important in the expression of autism. Assuming phenotypic differences between monozygotic twins are due to environmental influences may lead to mistaken conclusions regarding the relative genetic and environmental contribution to autism risk.

  1. Genetic and environmental effects on mortality before age 70 years

    DEFF Research Database (Denmark)

    Petersen, L.; Andersen, Per Kragh; Sørensen, Thorkild I.A.

    2008-01-01

    There is a familial influence on risk of many diseases and on mortality in general, which, according to studies of twins, is due to a combination of genetic and environmental effects. Adoption studies, which rest on different assumptions, may also be used to estimate separately the genetic...

  2. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    Science.gov (United States)

    Yiannakouris, Nikos; Katsoulis, Michail; Trichopoulou, Antonia; Ordovas, Jose M; Trichopoulos, Dimitrios

    2014-01-01

    Objectives An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for several conventional cardiovascular risk factors (ConvRFs), including smoking, hypertension, type-2 diabetes mellitus (T2DM), body mass index (BMI), physical activity and adherence to the Mediterranean diet. Design A case–control study. Setting The general Greek population of the EPIC study. Participants and outcome measures 477 patients with medically confirmed incident CHD and 1271 controls participated in this study. We estimated the ORs for CHD by dividing participants at higher or lower GRS and, alternatively, at higher or lower ConvRF, and calculated the relative excess risk due to interaction (RERI) as a measure of deviation from additivity. Results The joint presence of higher GRS and higher risk ConvRF was in all instances associated with an increased risk of CHD, compared with the joint presence of lower GRS and lower risk ConvRF. The OR (95% CI) was 1.7 (1.2 to 2.4) for smoking, 2.7 (1.9 to 3.8) for hypertension, 4.1 (2.8 to 6.1) for T2DM, 1.9 (1.4 to 2.5) for lower physical activity, 2.0 (1.3 to 3.2) for high BMI and 1.5 (1.1 to 2.1) for poor adherence to the Mediterranean diet. In all instances, RERI values were fairly small and not statistically significant, suggesting that the GRS and the ConvRFs do not have effects beyond additivity. Conclusions Genetic predisposition to CHD, operationalised through a multilocus GRS, and ConvRFs have essentially additive effects on CHD risk. PMID:24500614

  3. Cognitive vulnerability to depression : genetic and environmental influences

    NARCIS (Netherlands)

    Antypa, Niki

    2011-01-01

    This thesis explores cognitive vulnerability to depression and the interplay between genetic and environmental influences. Cognitive vulnerability to depression is characterized by negative patterns of information processing. One aspect is cognitive reactivity - the tendency to respond with

  4. Born to Lead? A Twin Design and Genetic Association Study of Leadership Role Occupancy*

    Science.gov (United States)

    De Neve, Jan-Emmanuel; Mikhaylov, Slava; Dawes, Christopher T.; Christakis, Nicholas A.; Fowler, James H.

    2013-01-01

    We address leadership emergence and the possibility that there is a partially innate predisposition to occupy a leadership role. Employing twin design methods on data from the National Longitudinal Study of Adolescent Health, we estimate the heritability of leadership role occupancy at 24%. Twin studies do not point to specific genes or neurological processes that might be involved. We therefore also conduct association analysis on the available genetic markers. The results show that leadership role occupancy is associated with rs4950, a single nucleotide polymorphism (SNP) residing on a neuronal acetylcholine receptor gene (CHRNB3). We replicate this family-based genetic association result on an independent sample in the Framingham Heart Study. This is the first study to identify a specific genotype associated with the tendency to occupy a leadership position. The results suggest that what determines whether an individual occupies a leadership position is the complex product of genetic and environmental influences; with a particular role for rs4950. PMID:23459689

  5. Genetic and environmental influences on cardiovascular risk factors and cognitive function

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Tian, Xiaocao; Sun, Jianping

    2018-01-01

    AIM: To explore the genetic and environmental influences on cardiovascular risk factors (CVRF) and cognitive function in the world's largest and rapidly aging Chinese population. METHODS: Cognitive function and CVRF, including body mass index, systolic blood pressure, diastolic blood pressure......, pulse pressure, glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol were measured in 379 complete twin pairs. Univariate and bivariate twin models were fitted to estimate the genetic and environmental components in the variance...... and covariance of CVRF and cognition. RESULTS: Mild-to-high heritability was estimated for CVRF and cognition (0.27-0.74). Unique environmental factors showed low-to-moderate contributions (0.23-0.56). Only HDLC presented significant common environmental contribution (0.50). Bivariate analysis showed...

  6. Genetic and environmental influences on affiliation with deviant peers during adolescence and early adulthood.

    Science.gov (United States)

    Tarantino, Nicholas; Tully, Erin C; Garcia, Sarah E; South, Susan; Iacono, William G; McGue, Matt

    2014-03-01

    Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youths exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence has suggested that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, changes in the relative importance of these factors, and which of these factors contribute to the stability of affiliation across this critical developmental period using a longitudinal twin study design that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3 discrete ages: 15, 18, and 21 years of age. Biometric models revealed that genetic influences increased with age. New genetic influences appeared during late adolescence, and no new genetic influences emerged by age 21. Environmental influences shared by sibling pairs decreased with age, while the proportion of nonshared environmental effects unique to each individual remained relatively stable over the course of development. Shared environmental influences were largely age-overlapping, whereas nonshared environmental influences were largely age-specific. In summary, this study found variance in affiliation with deviant peers is explained by shared and nonshared environment effects as well as by genetic influences (46% by age 21), supporting the role of genetically influenced selection factors. The shared environment was almost exclusively responsible for the stability in late adolescence, while genetic influences were primarily responsible for stability in early adulthood. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  7. Dataset on genetic and physiological adults׳ responses to social distress.

    Science.gov (United States)

    Bonassi, Andrea; Ghilardi, Tommaso; Truzzi, Anna; Cataldo, Ilaria; Azhari, Atiqah; Setoh, Peipei; Shinohara, Kazuyuki; Esposito, Gianluca

    2017-08-01

    Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR) and serotonin transporter (5-HTTLPR) polymorphisms), and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos) we assessed participants׳ ( N = 42 males) heart rate (HR) and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants' interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994[1]), and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]). To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298) and the 5-HTTLPR gene (region SLC6A4) were genotyped. The data set is made publicly available to enable critical or extended analyzes.

  8. Dataset on genetic and physiological adults׳ responses to social distress

    Directory of Open Access Journals (Sweden)

    Andrea Bonassi

    2017-08-01

    Full Text Available Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR and serotonin transporter (5-HTTLPR polymorphisms, and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos we assessed participants׳ (N = 42 males heart rate (HR and peripheral nose temperature, which index state of arousal and readiness to action. Self-reported questionnaires were used to evaluate participants’ interactional patterns towards peers (Attachment Style Questionnaire, Feeney et al., 1994 [1], and the quality of bond with intimate partners (Experiences in Close Relationships Scale, Fraley et al., 2000 [2]. To assess participants׳ genetic predispositions, the OXTR gene (regions rs53576, and rs2254298 and the 5-HTTLPR gene (region SLC6A4 were genotyped. The data set is made publicly available to enable critical or extended analyzes.

  9. Genetic and environmental factors in experimental and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.

    1980-01-01

    Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.

  10. EDITORIAL Clinical issues in genetic testing for multifactorial diseases

    African Journals Online (AJOL)

    Given the importance of MDs, detection of genetic predisposition is potentially attractive ... burden for affected individuals and families: disease is often early onset and ... to detection of BRCA-related breast cancer in a local public health sector.

  11. A deficiency in chromatin repair, genetic instability, and predisposition to cancer

    International Nuclear Information System (INIS)

    Sanford, K.K.; Parshad, R.; Gantt, R.R.; Tarone, R.E.

    1989-01-01

    This review traces steps leading to malignant neoplastic transformation of rodent and human cells in culture and in vivo. Emphasis is placed on an abnormal response characterized by persistent chromatid damage following irradiation of cells in culture with X-rays or fluorescent light during G2 phase of the cell cycle. Evidence is presented that deficient or unbalanced DNA repair during G2 accounts for the abnormal response. This G2 repair deficiency can be inherited or acquired by normal tissue cells during the process of or following attainment of infinite lifespan. It appears as an early, possibly initiating step in neoplastic transformation. It characterizes all human tumor cells examined irrespective of histopathology or tissue of origin. It has a genetic basis. In an animal model, the BALB/c mouse, this phenotype is associated with genes on chromosomes 1 and 4. It characterizes skin fibroblasts and blood lymphocytes from individuals with genetic or familial conditions predisposing to cancer and can be used to identify clinically normal family members carrying a gene(s) for any one of the three cancer-prone genetic disorders studied to date. Furthermore, it can provide the basis of a test for carriers of genes predisposing to a high risk of cancer. We conclude that the G2 repair deficiency, whether inherited or acquired, is a prerequisite for cancer development and that it accounts for the genetic instability of the cancer cell. 167 refs

  12. The structure of genetic and environmental risk factors for fears and phobias.

    Science.gov (United States)

    Loken, E K; Hettema, J M; Aggen, S H; Kendler, K S

    2014-08-01

    Although prior genetic studies of interview-assessed fears and phobias have shown that genetic factors predispose individuals to fears and phobias, they have been restricted to the DSM-III to DSM-IV aggregated subtypes of phobias rather than to individual fearful and phobic stimuli. We examined the lifetime history of fears and/or phobias in response to 21 individual phobic stimuli in 4067 personally interviewed twins from same-sex pairs from the Virginia Adult Twin Study of Psychiatric and Substance Abuse Disorders (VATSPSUD). We performed multivariate statistical analyses using Mx and Mplus. The best-fitting model for the 21 phobic stimuli included four genetic factors (agora-social-acrophobia, animal phobia, blood-injection-illness phobia and claustrophobia) and three environmental factors (agora-social-hospital phobia, animal phobia, and situational phobia). This study provides the first view of the architecture of genetic and environmental risk factors for phobic disorders and their subtypes. The genetic factors of the phobias support the DSM-IV and DSM-5 constructs of animal and blood-injection-injury phobias but do not support the separation of agoraphobia from social phobia. The results also do not show a coherent genetic factor for the DSM-IV and DSM-5 situational phobia. Finally, the patterns of co-morbidity across individual fears and phobias produced by genetic and environmental influences differ appreciably.

  13. Sex differences in genetic and environmental influences on educational attainment and income.

    Science.gov (United States)

    Orstavik, Ragnhild E; Czajkowski, Nikolai; Røysamb, Espen; Knudsen, Gun Peggy; Tambs, Kristian; Reichborn-Kjennerud, Ted

    2014-12-01

    In many Western countries, women now reach educational levels comparable to men, although their income remains considerably lower. For the past decades, it has become increasingly clear that these measures of socio-economic status are influenced by genetic as well as environmental factors. Less is known about the relationship between education and income, and sex differences. The aim of this study was to explore genetic and environmental factors influencing education and income in a large cohort of young Norwegian twins, with special emphasis on gender differences. National register data on educational level and income were obtained for 7,710 twins (aged 29-41 years). Bivariate Cholesky models were applied to estimate qualitative and quantitative gender differences in genetic and environmental influences, the relative contribution of genetic and environmental factors to the correlation between education and income, and genetic correlations within and between sexes and phenotypes. The phenotypic correlation between educational level and income was 0.34 (0.32-0.39) for men and 0.45 (0.43-0.48) for women. An ACE model with both qualitative and quantitative sex differences fitted the data best. The genetic correlation between men and women (rg) was 0.66 (0.22-1.00) for educational attainment and 0.38 (0.01-0.75) for income, and between the two phenotypes 0.31 (0.08-0.52) for men and 0.72 (0.64-0.85) for women. Our results imply that, in relatively egalitarian societies with state-supported access to higher education and political awareness of gender equality, genetic factors may play an important role in explaining sex differences in the relationship between education and income.

  14. The Influence of Familial Predisposition to Cardiovascular Complications upon Childhood Obesity Treatment

    DEFF Research Database (Denmark)

    Nielsen, Louise A; Bøjsøe, Christine; Kloppenborg, Julie T

    2015-01-01

    INTRODUCTION: The aim was to investigate whether a familial predisposition to obesity related cardiovascular complications was associated with the degree of obesity at baseline and/or changes in the degree of obesity during a multidisciplinary childhood obesity treatment program. METHODS: The study...... included 1421 obese children (634 boys) with a median age of 11.5 years (range 3.1-17.9 years), enrolled in treatment for 0.04 to 5.90 years (median 1.3 years) at the Children's Obesity Clinic, Denmark. At baseline, weight and height were measured, body mass index (BMI) standard deviation score (SDS......) calculated, and self-reported information on familial predisposition to obesity, hypertension, type 2 diabetes mellitus (T2DM), thromboembolic events, and dyslipidaemia were obtained. A familial predisposition included events in biological parents, siblings, grandparents, uncles, and aunts. The treatment...

  15. Genetic and environmental contributions to hay fever among young adult twins

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; Suppli Ulrik, Charlotte; Kyvik, Kirsten Ohm

    2006-01-01

    environment, whereas the aetiology of 'sporadic' hay fever was mainly genetic. CONCLUSIONS: The susceptibility to develop hay fever is attributable to major genetic influences. However, effects of family environment and upbringing are also of importance in families where asthma is present. These results......BACKGROUND: The susceptibility to develop hay fever is putatively the result both of genetic and environmental causes. We estimated the significance and magnitude of genetic and environmental contributions to hay fever among young adult twins. METHODS: From the birth cohorts 1953-82 of The Danish...... effects accounted for 29% of the individual susceptibility to hay fever. The same genes contributed to the susceptibility to hay fever both in males and in females. In families with asthma, the susceptibility to develop hay fever was, in addition to genes, to a great extent ascribable to family...

  16. Genetic and environmental influences on height from infancy to early adulthood

    DEFF Research Database (Denmark)

    Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi

    2016-01-01

    Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180......,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence...... (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across...

  17. Influence of race/ethnicity on genetic counseling and testing for hereditary breast and ovarian cancer.

    Science.gov (United States)

    Forman, Andrea D; Hall, Michael J

    2009-01-01

    Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.

  18. Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

    Science.gov (United States)

    Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

    2014-08-01

    The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Genetic and Environmental Effects on Vocal Symptoms and Their Intercorrelations

    Science.gov (United States)

    Nybacka, Ida; Simberg, Susanna; Santtila, Pekka; Sala, Eeva; Sandnabba, N. Kenneth

    2012-01-01

    Purpose: Recently, Simberg et al. (2009) found genetic effects on a composite variable consisting of 6 vocal symptom items measuring dysphonia. The purpose of the present study was to determine genetic and environmental effects on the individual vocal symptoms in a population-based sample of Finnish twins. Method: The sample comprised 1,728 twins…

  20. Genetic and Environmental Contributions to the Development of Childhood Aggression

    Science.gov (United States)

    Lubke, Gitta H.; McArtor, Daniel B.; Boomsma, Dorret I.; Bartels, Meike

    2018-01-01

    Longitudinal data from a large sample of twins participating in the Netherlands Twin Register (n = 42,827, age range 3-16) were analyzed to investigate the genetic and environmental contributions to childhood aggression. Genetic auto-regressive (simplex) models were used to assess whether the same genes are involved or whether new genes come into…

  1. The Relationship Between the Genetic and Environmental Influences on Common Externalizing Psychopathology and Mental Wellbeing

    Science.gov (United States)

    Kendler, Kenneth S.; Myers, John M.; Keyes, Corey L. M.

    2012-01-01

    To determine the relationship between the genetic and environmental risk factors for externalizing psychopathology and mental wellbeing, we examined detailed measures of emotional, social and psychological wellbeing, and a history of alcohol-related problems and smoking behavior in the last year in 1,386 individual twins from same-sex pairs from the MIDUS national US sample assessed in 1995. Cholesky decomposition analyses were performed with the Mx program. The best fit model contained one highly heritable common externalizing psychopathology factor for both substance use/abuse measures, and one strongly heritable common factor for the three wellbeing measures. Genetic and environmental risk factors for externalizing psychopathology were both negatively associated with levels of mental wellbeing and accounted for, respectively, 7% and 21% of its genetic and environmental influences. Adding internalizing psychopathology assessed in the last year to the model, genetic risk factors unique for externalizing psychopathology were now positively related to levels of mental wellbeing, although accounting for only 5% of the genetic variance. Environmental risk factors unique to externalizing psychopathology continued to be negatively associated with mental wellbeing, accounting for 26% of the environmental variance. When both internalizing psychopathology and externalizing psychopathology are associated with mental wellbeing, the strongest risk factors for low mental wellbeing are genetic factors that impact on both internalizing psychopathology and externalizing psychopathology, and environmental factors unique to externalizing psychopathology. In this model, genetic risk factors for externalizing psychopathology predict, albeit weakly, higher levels of mental wellbeing. PMID:22506307

  2. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

    NARCIS (Netherlands)

    Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Gómez García, Encarna; Ruijs, Mariëlle; Verhoef, Senno

    2009-01-01

    The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

  3. Divorce: An Unreliable Predictor of Children's Emotional Predispositions.

    Science.gov (United States)

    Bernard, Janine M.; Nesbitt, Sally

    1981-01-01

    Used the Children's Emotion Projection Instrument to investigate the emotional predispositions of children from divorce or disruption and children from intact families. Results indicated that children of divorce or disruption are not more hampered emotionally than children from intact families. Discusses implications for family therapists.…

  4. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    International Nuclear Information System (INIS)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Kerr, Iain D.; Min, Jinrong

    2015-01-01

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants

  5. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  6. Genetic predisposition scores for dyslipidaemia influence plasma lipid concentrations at baseline, but not the changes after controlled intake of n-3 polyunsaturated fatty acids.

    Science.gov (United States)

    AlSaleh, Aseel; Maniou, Zoitsa; Lewis, Fiona J; Hall, Wendy L; Sanders, Thomas A B; O'Dell, Sandra D

    2014-07-01

    Inconsistent effects of fish oil supplementation on plasma lipids may be influenced by genetic variation. We investigated 12 single nucleotide polymorphisms (SNPs) associated with dyslipidaemia in genome-wide association studies, in 310 participants randomised to treatment with placebo or 0.45, 0.9 and 1.8 g/day eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) (1.51:1) in a 12-month parallel controlled trial. Effects of risk alleles were assessed as trait-specific genetic predisposition scores (GPS) and singly. GPS were positively associated with baseline concentrations of plasma total cholesterol, low-density-lipoprotein cholesterol and triglyceride (TG) and negatively with high-density-lipoprotein cholesterol. The TG-GPS was associated with 0.210 mmol/L higher TG per risk allele (P GPS was associated with 0.023 mmol/L lower TG per risk allele (P = 0.72). No interactions between GPS and treatment were significant; however, FADS1 SNP rs174546 C/T interaction with treatment was a significant determinant of plasma TG concentration (P = 0.047, n = 267). Concentration differed between genotype groups after the 1.8 g/day dose (P = 0.026), decreasing by 3.5 (95 % CI -15.1 to 8.2) % in non-carriers of the risk T-allele (n = 30) and by 21.6 (95 % CI -32.1 to -11.2) % in carriers (n = 37), who showed a highly significant difference between treatments (P = 0.007). Carriers of the FADS1 rs174546 risk allele could benefit from a high intake of EPA and DHA in normalising plasma TG.

  7. Phenotypic, genetic, and environmental relationships between self-reported talents and measured intelligence.

    Science.gov (United States)

    Schermer, Julie Aitken; Johnson, Andrew M; Jang, Kerry L; Vernon, Philip A

    2015-02-01

    The relationship between self-report abilities and measured intelligence was examined at both the phenotypic (zero-order) level as well as at the genetic and environmental levels. Twins and siblings (N = 516) completed a timed intelligence test and a self-report ability questionnaire, which has previously been found to produce 10 factors, including: politics, interpersonal relationships, practical tasks, intellectual pursuits, academic skills, entrepreneur/business, domestic skills, vocal abilities, and creativity. At the phenotypic level, the correlations between the ability factor scores and intelligence ranged from 0.01 to 0.42 (between self-report academic abilities and verbal intelligence). Further analyses found that some of the phenotypic relationships between self-report ability scores and measured intelligence also had significant correlations at the genetic and environmental levels, suggesting that some of the observed relationships may be due to common genetic and/or environmental factors.

  8. Shared genetic and environmental influences on early temperament and preschool psychiatric disorders in Hispanic twins.

    Science.gov (United States)

    Silberg, Judy L; Gillespie, Nathan; Moore, Ashlee A; Eaves, Lindon J; Bates, John; Aggen, Steven; Pfister, Elizabeth; Canino, Glorisa

    2015-04-01

    Despite an increasing recognition that psychiatric disorders can be diagnosed as early as preschool, little is known how early genetic and environmental risk factors contribute to the development of psychiatric disorders during this very early period of development. We assessed infant temperament at age 1, and attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and separation anxiety disorder (SAD) at ages 3 through 5 years in a sample of Hispanic twins. Genetic, shared, and non-shared environmental effects were estimated for each temperamental construct and psychiatric disorder using the statistical program MX. Multivariate genetic models were fitted to determine whether the same or different sets of genes and environments account for the co-occurrence between early temperament and preschool psychiatric disorders. Additive genetic factors accounted for 61% of the variance in ADHD, 21% in ODD, and 28% in SAD. Shared environmental factors accounted for 34% of the variance in ODD and 15% of SAD. The genetic influence on difficult temperament was significantly associated with preschool ADHD, SAD, and ODD. The association between ODD and SAD was due to both genetic and family environmental factors. The temperamental trait of resistance to control was entirely accounted for by the shared family environment. There are different genetic and family environmental pathways between infant temperament and psychiatric diagnoses in this sample of Puerto Rican preschool age children.

  9. Genetic and environmental effects on body mass index from infancy to the onset of adulthood

    DEFF Research Database (Denmark)

    Silventoinen, Karri; Jelenkovic, Aline; Sund, Reijo

    2016-01-01

    BACKGROUND: Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. OBJECTIVES: We analyzed the genetic and environmental contributions to BMI variation from infancy...... were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. RESULTS: The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive...... environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained...

  10. Sex Differences in Genetic and Environmental Influences on Adolescent Depressive Symptoms: A Meta-Analytic Review

    Directory of Open Access Journals (Sweden)

    Jie Chen

    2015-01-01

    Full Text Available Although sex difference in the mean level of depressive symptoms has been well established, the sex difference in genetic and environmental influences on adolescent depressive symptoms is unclear. The current study conducted a meta-analysis of twin studies on sex differences in self- and parent-reported adolescent depressive symptoms. For self-reports, genetic factors influenced adolescent depressive symptoms equally for boys and girls, accounting for 46% of variation, but shared environmental factors had stronger impacts on adolescent girls’ versus boys’ depressive symptoms (13% versus 1% of the variance. For parent-reports, genetic, shared, and nonshared environmental factors influenced adolescent depressive symptoms equally, with separate estimates of 34%, 35%, and 31%. The implications of sex difference in genetic and environmental etiologies of depressive symptoms are discussed.

  11. Stocking the genetic supermarket: reproductive genetic technologies and collective action problems.

    Science.gov (United States)

    Gyngell, Chris; Douglas, Thomas

    2015-05-01

    Reproductive genetic technologies (RGTs) allow parents to decide whether their future children will have or lack certain genetic predispositions. A popular model that has been proposed for regulating access to RGTs is the 'genetic supermarket'. In the genetic supermarket, parents are free to make decisions about which genes to select for their children with little state interference. One possible consequence of the genetic supermarket is that collective action problems will arise: if rational individuals use the genetic supermarket in isolation from one another, this may have a negative effect on society as a whole, including future generations. In this article we argue that RGTs targeting height, innate immunity, and certain cognitive traits could lead to collective action problems. We then discuss whether this risk could in principle justify state intervention in the genetic supermarket. We argue that there is a plausible prima facie case for the view that such state intervention would be justified and respond to a number of arguments that might be adduced against that view. © 2014 The Authors. Bioethics published by John Wiley & Sons Ltd.

  12. Genetics, environment, and asthma associated with celiac disease in the extended family of an affected child.

    Science.gov (United States)

    Sigala-Robles, R; Aguayo-Patrón, S V; Calderón de la Barca, A M

    2017-11-18

    Celiac disease (CD) is an autoimmune enteropathy associated with gluten ingestion. In extended families of celiac patients that live in close proximity of one another, shared genetic and environmental factors can predispose them to CD. The aim of this study was to provide evidence about the genetic and environmental factors involved in the development of CD in the extended family of a pediatric patient. The medical history, environmental conditions, and participant weight, height, and peripheral blood samples were evaluated. The HLA-DQ2/DQ8 haplotypes were genotyped through qPCR testing and the IgA anti-gliadin and anti-transglutaminase antibodies were quantified using the ELISA test. Twelve close-living maternal relatives of the index case participated in the study. Eight of them presented with the HLA-DQ2 haplotype, inherited from the grandfather, and 7/12 and 9/12 were positive for IgA anti-gliadin and IgA anti-transglutaminase antibodies, respectively. The main intestinal symptoms stated by the participants were abdominal bloating, excess flatulence, constipation, and gastroesophageal reflux. The most frequent extra-intestinal symptoms were fatigue, stress, and anxiety. In addition, 6/13 participants had bronchial asthma. The extended family living in close proximity of one another shared a genetic predisposition, environmental conditions, and asthma, which could have predisposed them to celiac disease. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  13. Genetic and environmental effects on performance traits of ...

    African Journals Online (AJOL)

    Genetic and environmental effects on performance traits of Simmentaler cattle on the Transvaal Highveld. Tina Rust, J van der Westhuizen. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · AJOL African Journals Online. HOW TO USE ...

  14. Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

    Science.gov (United States)

    Bergin, Jocilyn E.; Kendler, Kenneth S.

    2012-01-01

    Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

  15. Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

    Science.gov (United States)

    Bergin, Jocilyn E; Kendler, Kenneth S

    2012-08-01

    Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

  16. Relationships between parenting and adolescent adjustment over time: genetic and environmental contributions.

    Science.gov (United States)

    Neiderhiser, J M; Reiss, D; Hetherington, E M; Plomin, R

    1999-05-01

    The predictive association between parenting and adolescent adjustment has been assumed to be environmental; however, genetic and environmental contributions have not been examined. This article represents one effort to examine these associations in which a genetically informative design was used. Participants were 395 families with adolescent siblings who participated in the Nonshared Environment in Adolescent Development (D. Reiss et al., 1994) project at 2 times of assessment, 3 years apart. There were 5 sibling types in 2 types of families: 63 identical twins, 75 fraternal twins, and 58 full siblings in nondivorced families and 95 full, 60 half, and 44 genetically unrelated siblings in stepfamilies. Results indicate that the cross-lagged associations between parental conflict-negativity and adolescent antisocial behavior and depressive symptoms can be explained primarily by genetic factors. These findings emphasize the need to recognize and examine the impact that adolescents have on parenting and the contribution of genetic factors to developmental change.

  17. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

    Directory of Open Access Journals (Sweden)

    Petroula Proitsi

    2014-09-01

    Full Text Available Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD and test the hypothesis that genetically raised lipid levels increase the risk of LOAD.We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578. We constructed weighted genotype risk scores (GRSs for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013. Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol. Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance.Genetic predisposition to increased blood cholesterol and

  18. Genetic and familial environmental effects on suicide attempts

    DEFF Research Database (Denmark)

    Petersen, Liselotte; Sørensen, Thorkild I A; Andersen, Per Kragh

    2014-01-01

    OBJECTIVES: Genetic factors have been found to influence the risk of suicide. It is less clear if this also applies to attempted suicide. We have investigated genetic and familial environmental factors by studying the occurrence of suicide attempts in biological and adoptive siblings of adoptees...... who attempted suicide compared to siblings of adoptees with no suicide attempts. METHOD: We used a random sample of 1933 adoptees from the Danish Adoption Register, a register of non-familial adoptions of Danish children, i.e. the adoptive parents are biologically unrelated to the adoptee. Analyses...... admission of siblings the increased rate was statistically significant (IRR=3.88; 95% CI-1.42-10.6). LIMITATIONS: Information on attempted suicide and psychiatric history was limited to that which involved hospitalisation. CONCLUSIONS: Genetic factors influence risk of suicide attempts....

  19. External apical root resorption concurrent with orthodontic forces: the genetic influence.

    Science.gov (United States)

    Nieto-Nieto, Nuria; Solano, Jose Enrique; Yañez-Vico, Rosa

    2017-05-01

    Root resorption is a pathological process of multifactorial origin related to the permanent loss of dental root structure in response to a mechanical, inflammatory, autoimmune or infectious stimulus. External apical root resorption (EARR) is a frequent clinical complication secondary to orthodontic tooth movement; apart from variables related to treatment, environmental factors and/or interindividual genetic variations can confer susceptibility or resistance to its occurrence. In this context, genetic predisposition has been described as an etiological factor, together with mechanical factors derived from orthodontic treatment. In recent years, international research groups have determined the degree of influence of some genetic biomarkers in defining increased/reduced susceptibility to postorthodontic EARR. The influences of the IL1 gene cluster (IL1B, IL1A, IL1RN, IL6), P2RX7, CASP1, OPG (TNFRSF11B), RANK (TNFRSF11A), Osteopontin (OPN), TNFα, the vitamin D receptor (TaqI), TNSALP and IRAK1 have been analyzed. The objective of the present review study was to compile and analyze the latest information about the genetic background predisposing to EARR during orthodontic treatment. Genetics-based studies along with other basic science research in the field might help to clarify the exact nature of EARR, the influence of genetic inheritance and possibly lead to the prevention or even eradication of this phenomenon during orthodontic treatment.

  20. Genetic and Environmental Associations Between Procrastination and Internalizing/Externalizing Psychopathology.

    Science.gov (United States)

    Gustavson, Daniel E; du Pont, Alta; Hatoum, Alexander S; Hyun Rhee, Soo; Kremen, William S; Hewitt, John K; Friedman, Naomi P

    2017-09-01

    Recent work on procrastination has begun to unravel the genetic and environmental correlates of this problematic behavior. However, little is known about how strongly procrastination is associated with internalizing and externalizing psychopathology, and the extent to which shared genetic/environmental factors or relevant personality constructs (e.g., fear of failure, impulsivity, and neuroticism) can inform the structure of these associations. The current study examined data from 764 young adult twins who completed questionnaires assessing procrastination and personality and structured interviews regarding psychopathology symptoms. Results indicated that procrastination was positively correlated with both internalizing and externalizing latent variables, and that these correlations were driven by shared genetic influences. Moreover, the association between procrastination and internalizing was accounted for by fear of failure and neuroticism, whereas the association between procrastination and externalizing was primarily explained by impulsivity. The role of procrastination in psychopathology is discussed using a framework that highlights common and broadband-specific variance.

  1. Environmental and genetic factors affecting faecal worm egg counts ...

    African Journals Online (AJOL)

    Environmental and genetic factors affecting faecal worm egg counts in Merinos divergently selected for reproduction. ... The fixed effect of birth year x sex interaction was significant, with rams showing higher mean values for FWEC than ewes ...

  2. Neuroimmunomodulation of the young brain. Nutrition, a gut feeling

    NARCIS (Netherlands)

    de Theije, C.G.M.

    2014-01-01

    Neurodevelopmental disorders, such as autism spectrum disorder (ASD), are heterogeneous conditions, in which both genetic predisposition and environmental factors play a role. Prenatal environmental factors such as maternal immune activation, deficient nutrition, and drugs use during pregnancy

  3. Environmental Moderators of Genetic Influences on Adolescent Delinquent Involvement and Victimization

    Science.gov (United States)

    Beaver, Kevin M.

    2011-01-01

    A growing body of empirical research reveals that genetic factors account for a substantial amount of variance in measures of antisocial behaviors. At the same time, evidence is also emerging indicating that certain environmental factors moderate the effects that genetic factors have on antisocial outcomes. Despite this line of research, much…

  4. Genetic and environmental effects on performance traits of ...

    African Journals Online (AJOL)

    Genetic and environmental effects on performance traits of Simmentaler cattle on the Transvaal Highveld. Tina Rust*. Highveld Region Agricultural Development Institute, .... ef'fect of the mtt' management system (m = 1,2,3,4),. bW = linear regression of the appropriate deviation from the mean of individual age at weaning (in ...

  5. Genetic and environmental risk factors in adolescent substance use.

    Science.gov (United States)

    Silberg, Judy; Rutter, Michael; D'Onofrio, Brian; Eaves, Lindon

    2003-07-01

    The present study was undertaken with the goal of understanding the causes of association between substance use and both conduct disturbance (CD) and depression in adolescent boys and girls. Multivariate genetic structural equation models were fitted to multi-informant, multi-wave, longitudinal data collected in extensive home interviews with parents and children with respect to 307 MZ male, 392 MZ female, 185 DZ male, and 187 DZ female, same-sex twin pairs aged 12-17 years from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Although conduct disturbance and depression were moderately associated with substance use, the pattern of genetic and environmental risk differed for males and females and across the two disorders. Genetic factors were predominant in girls' substance use whereas boys' use was mediated primarily by shared environmental factors reflecting family dysfunction and deviant peers. The patterns of correlations across the two waves of the study were consistent with conduct disturbance leading to substance use in both males and females, but depression leading to smoking, drug use and, to a lesser extent, alcohol use in girls. The comorbidity between substance use and depression, and between substance use and conduct disturbance in childhood/adolescence, probably reflects rather different mediating mechanisms--as well as a different time frame, with conduct disturbance preceding substance use but depression following it. In both, the co-occurrence partially reflected a shared liability but, in girls, genetic influences played an important role in the comorbidity involving depression, whereas in both sexes (but especially in boys) environmental factors played a substantial role. The extent to which these differences reflect genuine differences in the causal mechanisms underlying substance use and CD/depression in boys and girls revealed in the present analysis awaits replication from studies of other general population samples.

  6. Evaluation criteria of the individual motor predisposition of female sport gymnastics

    Directory of Open Access Journals (Sweden)

    Boraczynski T.

    2010-10-01

    Full Text Available In the paper were presented the results of research, aimed to improve criteria for assessing the motor predisposition of girls in sports gymnastics at the initial stage of training. The studies included 24 gymnasts divided into two age groups: A 6,0-7,5 years of age and B (8,3-13,0. The level of physical fitness was assessed with the use of the EUROFIT battery tests. easurements of the maximum moment of muscle strength in the bending forearm in the elbow joint in terms of isometric contraction were also performed. Assessment f the level of individual strengthspeed and coordination abilities and physical fitness structure including the pace of biological development were the basis for the development of objective criteria for assessing the sports predispositions of young gymnasts at the initial stage of training. Our results provide the basis for improving the control system and optimization of assessment criteria in women gymnastics, including age, training experience and sports level. The results presented in this paper demonstrated the usefulness of the research methodology used to assess the physical fitness and predispositions of gymnasts at the initial stage of training, what enables individualization of training process.

  7. Genetic and environmental influences on last-year major depression in adulthood: a highly heritable stable liability but strong environmental effects on 1-year prevalence.

    Science.gov (United States)

    Kendler, K S; Gardner, C O

    2017-07-01

    This study seeks to clarify the contribution of temporally stable and occasion-specific genetic and environmental influences on risk for major depression (MD). Our sample was 2153 members of female-female twin pairs from the Virginia Twin Registry. We examined four personal interview waves conducted over an 8-year period with MD in the last year defined by DSM-IV criteria. We fitted a structural equation model to the data using classic Mx. The model included genetic and environmental risk factors for a latent, stable vulnerability to MD and for episodes in each of the four waves. The best-fit model was simple and included genetic and unique environmental influences on the latent liability to MD and unique wave-specific environmental effects. The path from latent liability to MD in the last year was constant over time, moderate in magnitude (+0.65) and weaker than the impact of occasion-specific environmental effects (+0.76). Heritability of the latent stable liability to MD was much higher (78%) than that estimated for last-year MD (32%). Of the total unique environmental influences on MD, 13% reflected enduring consequences of earlier environmental insults, 17% diagnostic error and 70% wave-specific short-lived environmental stressors. Both genetic influences on MD and MD heritability are stable over middle adulthood. However, the largest influence on last-year MD is short-lived environmental effects. As predicted by genetic theory, the heritability of MD is increased substantially by measurement at multiple time points largely through the reduction of the effects of measurement error and short-term environmental risk factors.

  8. Health-related disparities: influence of environmental factors.

    Science.gov (United States)

    Olden, Kenneth; White, Sandra L

    2005-07-01

    populations, but their frequency can vary substantially,rendering individuals or groups more or less susceptible to particular environmental exposures. Such findings are consistent with the highly publicized analogy, "genetics loads the gun, but the environment pulls the trigger." That is, one can inherit the genetic predisposition to develop a disease but will do so only if or when exposed to the environmental trigger. Poor people have approximately the same genetic makeup as everyone else,but they have the unfortunate experience of living and working in environments containing multiple and high levels of carcinogens or other toxicants capable of interacting with susceptibility genes to cause disease.Furthermore, certain disadvantaged ethnic groups may have a higher incidence of certain susceptible genes that render them more vulnerable to adverse effects of the environments they inhabit. For both of these reasons,much of the nation's disease burden could likely be reduced through better environmental protection practices, especially in low-income and minority communities. Of the many implications of polymorphisms and frequency variations for public health and the practice of medicine, however, none is more urgent than the choice of drugs in therapy. Using such knowledge,randomized trials have identified race-specific drug response differences between blacks and whites [42].To date, most knowledge of the health effects of environmental factors is derived from studies of single agents. The reality, though, is that environmental contributions to health disparities are mostly from multiple agents. These simultaneous exposures to multiple risk factors, which may accumulate or interact synergistically, remain to be fully explained and defined.Finally, health disparity is a significant public health problem that cannot be solved using "business as usual" approaches for funding and priority setting. The current emphasis on basic and clinical research at the exclusion of public

  9. Evidence that periweaning failure-to-thrive syndrome (PFTS) has a genetic predisposition.

    Science.gov (United States)

    Ramis, G; Marco, E; Magaña, V; González-Contreras, P; Swierczynski, G; Abellaneda, J M; Sáez-Acosta, A; Mrowiec, A; Pallarés, F J

    2015-06-06

    Genetic susceptibility or resistance to diseases is currently drawing increasing attention. This work describes two different breeding herds showing signs of periweaning failure-to-thrive syndrome (PFTS), an emergent swine disease. The disease was diagnosed based on clinical picture and confirmed by histopathology. The possibility of main infectious pathogens was ruled out by immunohistochemistry and PCR. In a simple approach, sires of the affected piglets have been determined using microsatellite paternity analysis, including a healthy group in each case. In each of the two farms, a single boar was found to have sired 45-50 per cent sick animals. Removal of this sire from two farms resulted in a significant decrease in the prevalence of the disease among the offspring, in accordance with other two cases diagnosed, although without including a control group. Since the analysed animals belonged to three different genetic lines, these findings point to the existence of individual genetic susceptibility to this syndrome. British Veterinary Association.

  10. Effect of deregulation of Sonic Hedgehog pathway on responses to DNA damage and cancer predisposition

    International Nuclear Information System (INIS)

    Charazac, Aurelie

    2015-01-01

    The Gorlin syndrome is a rare genetic disorder characterized by several developmental abnormalities. Due to mutations in PTCH1, a key player of the sonic hedgehog signaling pathway, clinical manifestations also includes hyper-radiosensitivity and an increased predisposition to the development of basal cell carcinomas. Given the implication of DNA repair system defects in hyper-radiosensitivity pathologies, we decided to study the effect of PTCH1 mutations on the DNA damage response in order to better understand the cellular and molecular mechanisms leading to Gorlin's phenotype.This study demonstrate a global failure of the DNA damage repair systems in Gorlin fibroblasts with respect to controls. It highlights in particular the collapse of the base excision repair pathway (BER) responsible for the repair of oxidative DNA damage. (author) [fr

  11. Genetic and environmental origins of hypospadias

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Nordenskjöld, Agneta; Hutson, John M

    2014-01-01

    PURPOSE OF REVIEW: The purpose of this study was to review and comment on recent original presentations dealing with genetic and environmental factors in the cause of hypospadias. RECENT FINDINGS: The heritability is definitely high and having an affected family member is the highest identified...... of hypospadias with low birth weight, maternal hypertension, and preeclampsia suggests that placental insufficiency is a major risk factor. Maternal exposure to chemical pollutants or endocrine disruptors in high concentrations related to selected occupations or geographic areas may be additional risk factors...

  12. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

    International Nuclear Information System (INIS)

    Apalasamy, Y.D.; Ming, M.F.; Rampal, S.; Bulgiba, A.; Mohamed, Z.

    2012-01-01

    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays

  13. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

    Energy Technology Data Exchange (ETDEWEB)

    Apalasamy, Y.D. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Ming, M.F.; Rampal, S.; Bulgiba, A. [Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Mohamed, Z. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

    2012-08-24

    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  14. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

    Directory of Open Access Journals (Sweden)

    Y.D. Apalasamy

    2012-12-01

    Full Text Available The common variants in the fat mass- and obesity-associated (FTO gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs and linkage disequilibrium (LD blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0. In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  15. A genetic-epidemiologic study of Alzheimer’s disease

    NARCIS (Netherlands)

    A. Arias-Vásquez (Alejandro)

    2006-01-01

    textabstractAlzheimer's disease (AD) is the most frequent cause of dementia and thus is a major public-health problem. Age and genetic predisposition to the disease are the most important risk factors. In 2001 more than 24 million people in the western world had dementia. This number is expected to

  16. River predisposition to ice jams: a simplified geospatial model

    Directory of Open Access Journals (Sweden)

    S. De Munck

    2017-07-01

    Full Text Available Floods resulting from river ice jams pose a great risk to many riverside municipalities in Canada. The location of an ice jam is mainly influenced by channel morphology. The goal of this work was therefore to develop a simplified geospatial model to estimate the predisposition of a river channel to ice jams. Rather than predicting the timing of river ice breakup, the main question here was to predict where the broken ice is susceptible to jam based on the river's geomorphological characteristics. Thus, six parameters referred to potential causes for ice jams in the literature were initially selected: presence of an island, narrowing of the channel, high sinuosity, presence of a bridge, confluence of rivers, and slope break. A GIS-based tool was used to generate the aforementioned factors over regular-spaced segments along the entire channel using available geospatial data. An ice jam predisposition index (IJPI was calculated by combining the weighted optimal factors. Three Canadian rivers (province of Québec were chosen as test sites. The resulting maps were assessed from historical observations and local knowledge. Results show that 77 % of the observed ice jam sites on record occurred in river sections that the model considered as having high or medium predisposition. This leaves 23 % of false negative errors (missed occurrence. Between 7 and 11 % of the highly predisposed river sections did not have an ice jam on record (false-positive cases. Results, limitations, and potential improvements are discussed.

  17. [A twin study on genetic and environmental factors of adolescents violence behaviors].

    Science.gov (United States)

    Zhu, Wenfen; Fu, Yixiao; Hu, Xiaomei; Wang, Yingcheng; Deng, Wei; Li, Tao; Ma, Xingshun

    2015-11-01

    To explore the influence of genetic and environmental factors on adolescents violence behaviors. The violence behaviors of 111 twin pairs from Chongqing (aged from 11 to 18 years) were investigated with risk behavior questionnaire-adolescent (RBQ-A). The Parenting Styles and Dimensions Questionnaire (PSDQ) and Stressful Life Event (SLE) and the General Functioning Scale of the MacMaster Family Activity Device (FAD-GFS) were applied to assess their environment factors. Structural equation modeling was performed to evaluate the effects of the additive genetic factors (A), shared environment factors (C) and individual specific environmental factors (E) on the adolescents violence behaviors. The effects of A and E on adolescents violence behaviors were 0.41 (95% CI 0.19-0.58) and 0.59 (95% CI 0.42-0.81) respectively. There were significantly negative correlation between violence behaviors and authoritative-parenting-style (r = -0.140, P parenting-style score (r = 0.133, P parenting education level and occupation. Adolescents violence behaviors were influenced by additive genetic factors and individual specific environmental factors. Environmental plays an important role. It should not been ignored that parental rearing pattern play a role in adolescents violence behaviors.

  18. Genetic and environmental influences on the allocation of adolescent leisure time activities.

    Science.gov (United States)

    Haberstick, Brett C; Zeiger, Joanna S; Corley, Robin P

    2014-01-01

    There is a growing recognition of the importance of the out-of-school activities in which adolescents choose to participate. Youth activities vary widely in terms of specific activities and in time devoted to them but can generally be grouped by the type and total duration spent per type. We collected leisure time information using a 17-item leisure time questionnaire in a large sample of same- and opposite-sex adolescent twin pairs (N = 2847). Using both univariate and multivariate genetic models, we sought to determine the type and magnitude of genetic and environmental influences on the allocation of time toward different leisure times. Results indicated that both genetic and shared and nonshared environmental influences were important contributors to individual differences in physical, social, intellectual, family, and passive activities such as watching television. The magnitude of these influences differed between males and females. Environmental influences were the primary factors contributing to the covariation of different leisure time activities. Our results suggest the importance of heritable influences on the allocation of leisure time activity by adolescents and highlight the importance of environmental experiences in these choices.

  19. Genes and genetic variations involved in the development of hypertension: focusing on a Greek patient cohort.

    Science.gov (United States)

    Kouremenos, Nikolaos; Zacharopoulou, Ioanna V; Triantafyllidi, Helen; Zacharopoulos, Georgios V; Mornos, Cristian; Filippatos, Gerasimos; Lekakis, John; Kremastinos, Dimitrios; Manolis, Athanasios I; Gavras, Haralambos

    2014-01-01

    Essential hypertension (HTN) is a multifactorial disease involving environmental, genetic and other factors. Over the past years, genetic studies of essential HTN have increased dramatically but the molecular mechanisms involved are still unknown. As part of a research program coordinated by Boston university (USA), we studied the role of various genes and single nucleotide polymorphisms (SNPs) in the inheritance or the onset of HTN in African-American, Caucasian-American and Greek families. Among 128 Greek families with a history of HTN, we studied 1474 people. Of the total examined, 273 men and 286 women were hypertensive. Based on 410 DNA samples from the hypertensive subjects, different SNPs were examined. An overall meta-analysis of the results from the Greek families, as well as a comparison with the 2 other groups (African-Americans and Caucasian-Americans), was performed. We report SNPs that are associated with the inheritance of HTN and are located either at the promoters of N-methyltransferase and catalase genes, or within the coding region of NEDD4L ubiquitin ligase gene, or SNPs in mitochondrial DNA of hypertensive probands. Furthermore, we clarified the role of hereditary predisposition in the development of HTN, showing that the presence of maternal HTN was significantly higher in African-Americans and Greeks compared to Caucasian-Americans (81.7%, 84.8%, and 65%), while the paternal HTN showed no such difference (50%, 48.3% and 44.9%), respectively. Although genetic factors that were correlated with HTN were identified, it was not possible to identify a single gene that should be targeted for the treatment of HTN. Nevertheless, the important role of the maternal hereditary predisposition to HTN in the Greek patients and the responsible genetic factors involved should be further examined.

  20. Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood.

    Science.gov (United States)

    Wesseldijk, Laura W; Bartels, Meike; Vink, Jacqueline M; van Beijsterveldt, Catharina E M; Ligthart, Lannie; Boomsma, Dorret I; Middeldorp, Christel M

    2017-06-21

    Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and unique environmental factors on variation in conduct problems measured at childhood and adolescence and antisocial personality problems measured at adulthood and on the covariation across ages. We also tested whether these estimates differed by sex. Longitudinal data were collected in the Netherlands Twin Register over a period of 27 years. Age appropriate and comparable measures of conduct and antisocial personality problems, assessed with the Achenbach System of Empirically Based Assessment, were available for 9783 9-10-year-old, 6839 13-18-year-old, and 7909 19-65-year-old twin pairs, respectively; 5114 twins have two or more assessments. At all ages, men scored higher than women. There were no sex differences in the estimates of the genetic and environmental influences. During childhood, genetic and environmental factors shared by children in families explained 43 and 44% of the variance of conduct problems, with the remaining variance due to unique environment. During adolescence and adulthood, genetic and unique environmental factors equally explained the variation. Longitudinal correlations across age varied between 0.20 and 0.38 and were mainly due to stable genetic factors. We conclude that shared environment is mainly of importance during childhood, while genetic factors contribute to variation in conduct and antisocial personality problems at all ages, and also underlie its stability over age.

  1. Content, Structure, and Usefulness of Juvenile Predisposition Psychological Evaluations

    Science.gov (United States)

    Morin, Samantha L.; Cruise, Keith R.; Hinz, Holly; Holloway, Evan D.; Chapman, John F.

    2015-01-01

    Background: There is a dearth of research regarding the content and structure of juvenile predisposition psychological evaluations. Limited research suggests that key mental health domains are insufficiently represented and judges use evaluator recommendations regarding legal outcomes more often than clinical outcomes. Studies have not addressed…

  2. Integrating environmental and genetic effects to predict responses of tree populations to climate.

    Science.gov (United States)

    Wang, Tongli; O'Neill, Gregory A; Aitken, Sally N

    2010-01-01

    Climate is a major environmental factor affecting the phenotype of trees and is also a critical agent of natural selection that has molded among-population genetic variation. Population response functions describe the environmental effect of planting site climates on the performance of a single population, whereas transfer functions describe among-population genetic variation molded by natural selection for climate. Although these approaches are widely used to predict the responses of trees to climate change, both have limitations. We present a novel approach that integrates both genetic and environmental effects into a single "universal response function" (URF) to better predict the influence of climate on phenotypes. Using a large lodgepole pine (Pinus contorta Dougl. ex Loud.) field transplant experiment composed of 140 populations planted on 62 sites to demonstrate the methodology, we show that the URF makes full use of data from provenance trials to: (1) improve predictions of climate change impacts on phenotypes; (2) reduce the size and cost of future provenance trials without compromising predictive power; (3) more fully exploit existing, less comprehensive provenance tests; (4) quantify and compare environmental and genetic effects of climate on population performance; and (5) predict the performance of any population growing in any climate. Finally, we discuss how the last attribute allows the URF to be used as a mechanistic model to predict population and species ranges for the future and to guide assisted migration of seed for reforestation, restoration, or afforestation and genetic conservation in a changing climate.

  3. Detection of genetic variants affecting cattle behaviour and their impact on milk production: a genome-wide association study.

    Science.gov (United States)

    Friedrich, Juliane; Brand, Bodo; Ponsuksili, Siriluck; Graunke, Katharina L; Langbein, Jan; Knaust, Jacqueline; Kühn, Christa; Schwerin, Manfred

    2016-02-01

    Behaviour traits of cattle have been reported to affect important production traits, such as meat quality and milk performance as well as reproduction and health. Genetic predisposition is, together with environmental stimuli, undoubtedly involved in the development of behaviour phenotypes. Underlying molecular mechanisms affecting behaviour in general and behaviour and productions traits in particular still have to be studied in detail. Therefore, we performed a genome-wide association study in an F2 Charolais × German Holstein cross-breed population to identify genetic variants that affect behaviour-related traits assessed in an open-field and novel-object test and analysed their putative impact on milk performance. Of 37,201 tested single nucleotide polymorphism (SNPs), four showed a genome-wide and 37 a chromosome-wide significant association with behaviour traits assessed in both tests. Nine of the SNPs that were associated with behaviour traits likewise showed a nominal significant association with milk performance traits. On chromosomes 14 and 29, six SNPs were identified to be associated with exploratory behaviour and inactivity during the novel-object test as well as with milk yield traits. Least squares means for behaviour and milk performance traits for these SNPs revealed that genotypes associated with higher inactivity and less exploratory behaviour promote higher milk yields. Whether these results are due to molecular mechanisms simultaneously affecting behaviour and milk performance or due to a behaviour predisposition, which causes indirect effects on milk performance by influencing individual reactivity, needs further investigation. © 2015 Stichting International Foundation for Animal Genetics.

  4. Genetic and environmental sources of covariation between early drinking and adult functioning.

    Science.gov (United States)

    Waldron, Jordan Sparks; Malone, Stephen M; McGue, Matt; Iacono, William G

    2017-08-01

    The vast majority of individuals initiate alcohol consumption for the first time in adolescence. Given the widespread nature of its use and evidence that adolescents may be especially vulnerable to its effects, there is concern about the long-term detrimental impact of adolescent drinking on adult functioning. While some researchers have suggested that genetic processes may confound the relationship, the mechanisms linking drinking and later adjustment remain unclear. The current study utilized a genetically informed sample and biometric modeling to examine the nature of the familial influences on this association and identify the potential for genetic confounding. The sample was drawn from the Minnesota Twin Family Study (MTFS), a longitudinal study consisting of 2,764 twins assessed in 2 cohorts at regular follow-ups from age 17 to age 29 (older cohort) or age 11 to age 29 (younger cohort). A broad range of adult measures was included assessing substance use, antisocial behavior, personality, socioeconomic status, and social functioning. A bivariate Cholesky decomposition was used to examine the common genetic and environmental influences on adolescent drinking and each of the measures of adult adjustment. The results revealed that genetic factors and nonshared environmental influences were generally most important in explaining the relationship between adolescent drinking and later functioning. While the presence of nonshared environmental influences on the association are not inconsistent with a causal impact of adolescent drinking, the findings suggest that many of the adjustment issues associated with adolescent alcohol consumption are best understood as genetically influenced vulnerabilities. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Genetic and Environmental Contributions to General Cognitive Ability through the First 16 Years of Life

    Science.gov (United States)

    Petrill, Stephen A.; Lipton, Paul A.; Hewitt, John K.; Plomin, Robert; Cherny, Stacey S.; Corley, Robin; DeFries, John C.

    2004-01-01

    The genetic and environmental contributions to the development of general cognitive ability throughout the first 16 years of life were examined using sibling data from the Colorado Adoption Project. Correlations were analyzed along with structural equation models to characterize the genetic and environmental influences on longitudinal stability…

  6. Panel 3: Genetics and Precision Medicine of Otitis Media.

    Science.gov (United States)

    Lin, Jizhen; Hafrén, Hena; Kerschner, Joseph; Li, Jian-Dong; Brown, Steve; Zheng, Qing Y; Preciado, Diego; Nakamura, Yoshihisa; Huang, Qiuhong; Zhang, Yan

    2017-04-01

    Objective The objective is to perform a comprehensive review of the literature up to 2015 on the genetics and precision medicine relevant to otitis media. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels were formed comprising experts in the genetics and precision medicine of otitis media. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The entire panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 and discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion Many genes relevant to otitis media have been identified in the last 4 years in advancing our knowledge regarding the predisposition of the middle ear mucosa to commensals and pathogens. Advances include mutant animal models and clinical studies. Many signaling pathways are involved in the predisposition of otitis media. Implications for Practice New knowledge on the genetic background relevant to otitis media forms a basis of novel potential interventions, including potential new ways to treat otitis media.

  7. Genetic and Environmental Contributions to Cranial Capacity in Black and White Adolescents.

    Science.gov (United States)

    Rushton, J. Philippe; Osborne, R. Travis

    1995-01-01

    Data from 236 pairs of black twins and white twins aged 13-17 years were used to examine genetic and environmental factors influencing cranial size, an indirect estimate of brain volume. Genetic factors are required to account for the phenotypic variance in cranial capacity. (SLD)

  8. Genetic and environmental influences underlying the relationship between autistic traits and temperament and character dimensions in adulthood.

    Science.gov (United States)

    Picardi, Angelo; Fagnani, Corrado; Medda, Emanuela; Toccaceli, Virgilia; Brambilla, Paolo; Stazi, Maria Antonietta

    2015-04-01

    In recent years, several twin studies adopted a dimensional approach to Autism Spectrum Disorders (ASD) and estimated the contribution of genetic and environmental influences to variation in autistic traits. However, no study was performed on adults over 18 years of age and all but two studies were based on parent or teacher ratings. Also, the genetic and environmental contributions to the interplay between autistic traits and adult personality dimensions have not been investigated. A sample of 266 complete twin pairs (30% males, mean age 40 ± 12 years) drawn from the population-based Italian Twin Register was administered the Autism-Spectrum Quotient, Temperament and Character Inventory (TCI-125), and General Health Questionnaire (GHQ-12). Genetic structural equation modelling was performed with the Mx program. Estimates were adjusted for gender, age, and GHQ-12 score. Genetic factors accounted for 44% and 20%-49% of individual differences in autistic traits and TCI dimensions, respectively. Unshared environmental factors explained the remaining proportion of variance. Consistently with the notion of a personality profile in ASD characterised by obsessive temperament, autistic traits showed significant phenotypic correlations with several TCI dimensions (positive: HA; negative: NS, RD, SD, C). Genetic and unshared environmental correlations between AQ and these TCI dimensions were significant. The degree of genetic overlap was generally greater than the degree of environmental overlap. Despite some limitations, this study suggests that genetic factors contribute substantially to individual differences in autistic traits in adults, with unshared environmental influences also playing an important role. It also suggests that autistic traits and the majority of temperament and character dimensions share common genetic and environmental aetiological factors. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  10. Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

    NARCIS (Netherlands)

    van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

    2016-01-01

    BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND

  11. Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms

    NARCIS (Netherlands)

    van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

    2016-01-01

    Background--Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and

  12. Predisposition of Nigerian children with severe malaria to urinary ...

    African Journals Online (AJOL)

    The predisposition of children with severe malaria to urinary tract infection was investigated in a group of 112 clinically diagnosed and para sitologically confirmed severe malaria patients (test) and in another subset of 114 apparently physically healthy non-malaria infected subjects (control). Standard bacteriological and ...

  13. Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

    Directory of Open Access Journals (Sweden)

    Dębniak Tadeusz

    2007-06-01

    Full Text Available Abstract Based on epidemiological data we can assume that at least some malignant melanoma (MM and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.

  14. 75 FR 8299 - Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically...

    Science.gov (United States)

    2010-02-24

    ...] Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically... making a determination on the status of the Monsanto Company and Forage Genetics International alfalfa... status of the Monsanto Company and Forage Genetics International alfalfa lines designated as events J101...

  15. Genetic and environmental influences on the relation between parental social class and mortality

    DEFF Research Database (Denmark)

    Osler, Merete; Petersen, L.; Prescott, Eva Irene Bossano

    2006-01-01

    Genetic and maternal prenatal environmental factors as well as the post-natal rearing environment may contribute to the association between childhood socioeconomic circumstances and later mortality. In order to disentangle these influences, we studied all-cause and cause-specific mortality in a c...... in a cohort of adoptees, in whom we estimated the effects of their biological and adoptive fathers' social classes as indicators of the genetic and/or prenatal environmental factors and the post-natal environment, respectively....

  16. Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states.

    Science.gov (United States)

    Sprangers, Mirjam A G; Bartels, Meike; Veenhoven, Ruut; Baas, Frank; Martin, Nicholas G; Mosing, Miriam; Movsas, Benjamin; Ropka, Mary E; Shinozaki, Gen; Swaab, Dick

    2010-12-01

    In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states. Literature overview. The heritability estimates for anxiety and depression are 30-40%. Related traits as neuroticism and loneliness are also highly heritable. The hypothalamo-pituitary-adrenal axis is the 'final common pathway' for most depressive symptoms. The many findings of investigated genes are promising but not definitive. Heritability estimates of positive emotional states range between 40 and 50%. Life satisfaction and mental health share common genetic factors with optimism and self-esteem. The prefrontal cortex is a candidate brain area for positive emotional states. Biological and genetic research into positive emotional states is scarce. Genetically informative studies may provide insights into a wide variety of complex questions that traditional QL studies cannot deliver. This insight in turn will help us to design more effective supportive programs that could moderate the outcomes of genetically based predispositions.

  17. Genetic mutations in Gorlin-Goltz syndrome

    OpenAIRE

    Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

    2013-01-01

    Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management.

  18. Genetic mutations in Gorlin-Goltz syndrome.

    Science.gov (United States)

    Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

    2013-07-01

    Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management.

  19. Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

    International Nuclear Information System (INIS)

    Forjaz, C.L.M.; Bartholomeu, T.; Rezende, J.A.S.; Oliveira, J.A.; Basso, L.; Tani, G.; Prista, A.; Maia, J.A.R.

    2012-01-01

    Blood pressure (BP) and physical activity (PA) levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP was measured, and total PA (TPA) was assessed by an interview (commuting, occupational, leisure time, and school time PA). Quantitative genetic modeling was used to estimate maximal heritability (h 2 ), and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h 2 = 0.37 ± 0.10, P < 0.05; diastolic BP: h 2 = 0.39 ± 0.09, P < 0.05; TPA: h 2 = 0.24 ± 0.09, P < 0.05). Significant genetic (r g ) and environmental (r e ) correlations were detected between systolic and diastolic BP (r g = 0.67 ± 0.12 and r e = 0.48 ± 0.08, P < 0.05). Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r e = -0.18 ± 0.09, P = 0.057). In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences

  20. Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy.

    Science.gov (United States)

    Dubrovina, N I; Zinov'ev, D R; Zinov'eva, D V; Kulikov, A V

    2009-06-01

    This report presents results obtained from comparative analysis of learning and the dynamics of extinction of a conditioned passive avoidance response in ASC mice, which were bred for a high level of predisposition to catalepsy, and in CBA and AKR mice. The following findings were obtained: 1) impairments to the extinction of the memory of fear represent an important symptom of depression in ASC mice; 2) extinction is delayed in CBA mice; and 3) new inhibitory learning occurs quickly in AKR mice. Prolonged retention of the fear memory in ASC mice appears to be related to increased anxiety on prolonged testing without a punishment. The deficit of inhibition of the fear reaction in ASC mice allows this strain to be regarded as a genetic model of depression.

  1. Personality Predispositions to Depression in Children of Affectively-Ill Parents: The Buffering Role of Self-Esteem

    Science.gov (United States)

    Abela, John R. Z.; Fishman, Michael B.; Cohen, Joseph R.; Young, Jami F.

    2012-01-01

    A major theory of personality predispositions to depression posits that individuals who possess high levels of self-criticism and/or dependency are vulnerable to developing depression following negative life events. The goal of the current study was to test this theory of personality predispositions and the self-esteem buffering hypothesis in a…

  2. Epigenomic strategies at the interface of genetic and environmental risk factors for autism.

    Science.gov (United States)

    LaSalle, Janine M

    2013-07-01

    Autism spectrum disorders (ASD) have been increasing in prevalence over the last two decades, primarily because of increased awareness and diagnosis. However, autism is clearly a complex human genetic disorder that involves interactions between genes and environment. Epigenetic mechanisms, such as DNA methylation, act at the interface of genetic and environmental risk and protective factors. Advancements in genome-wide sequencing has broadened the view of the human methylome and revealed the organization of the human genome into large-scale methylation domains that footprint over neurologically important genes involved in embryonic development. Future integrative epigenomic analyses of genetic risk factors with environmental exposures and methylome analyses are expected to be important for understanding the complex etiology of ASD.

  3. Environmental and geographic variables are effective surrogates for genetic variation in conservation planning.

    Science.gov (United States)

    Hanson, Jeffrey O; Rhodes, Jonathan R; Riginos, Cynthia; Fuller, Richard A

    2017-11-28

    Protected areas buffer species from anthropogenic threats and provide places for the processes that generate and maintain biodiversity to continue. However, genetic variation, the raw material for evolution, is difficult to capture in conservation planning, not least because genetic data require considerable resources to obtain and analyze. Here we show that freely available environmental and geographic distance variables can be highly effective surrogates in conservation planning for representing adaptive and neutral intraspecific genetic variation. We obtained occurrence and genetic data from the IntraBioDiv project for 27 plant species collected over the European Alps using a gridded sampling scheme. For each species, we identified loci that were potentially under selection using outlier loci methods, and mapped their main gradients of adaptive and neutral genetic variation across the grid cells. We then used the cells as planning units to prioritize protected area acquisitions. First, we verified that the spatial patterns of environmental and geographic variation were correlated, respectively, with adaptive and neutral genetic variation. Second, we showed that these surrogates can predict the proportion of genetic variation secured in randomly generated solutions. Finally, we discovered that solutions based only on surrogate information secured substantial amounts of adaptive and neutral genetic variation. Our work paves the way for widespread integration of surrogates for genetic variation into conservation planning.

  4. Convergence of genetic and environmental factors on parvalbumin-positive interneurons in schizophrenia

    Directory of Open Access Journals (Sweden)

    Zhihong eJiang

    2013-09-01

    Full Text Available Schizophrenia etiology is thought to involve an interaction between genetic and environmental factors during postnatal brain development. However, there is a fundamental gap in our understanding of the molecular mechanisms by which environmental factors interact with genetic susceptibility to trigger symptom onset and disease progression. In this review, we summarize the most recent findings implicating oxidative stress as one mechanism by which environmental insults, especially early life social stress, impact the development of schizophrenia. Based on a review of the literature and the results of our own animal model, we suggest that environmental stressors such as social isolation render parvalbumin-positive interneurons vulnerable to oxidative stress. We previously reported that social isolation stress exacerbates many of the schizophrenia-like phenotypes seen in a conditional genetic mouse model of schizophrenia in which NMDARs are selectively ablated in half of cortical and hippocampal interneurons during early postnatal development (Belforte et al., 2010. We have since revealed that this social isolation-induced effect is caused by impairments in the antioxidant defense capacity in the parvalbumin-positive interneurons in which NMDARs are ablated. We propose that this effect is mediated by the down-regulation of PGC-1α, a master regulator of mitochondrial energy metabolism and anti-oxidant defense, following the deletion of NMDARs (Jiang et al, 2013. Other potential molecular mechanisms underlying redox dysfunction upon gene and environmental interaction will be discussed, with a focus on the unique properties of parvalbumin-positive interneurons.

  5. From predisposition to psychosis: progression of symptoms in schizophrenia

    DEFF Research Database (Denmark)

    Parnas, Josef

    1999-01-01

    Schizophrenia is increasingly viewed as a neurodevelopmental process caused by an interaction between genetic factors and environmental stressors. Prospective studies and retrospective research using objective data indicate that behavioural deviations can be dated to early infancy and cut across...

  6. A comparative study on genetic and environmental influences on metabolic phenotypes in Eastern (Chinese) and Western (Danish) populations

    DEFF Research Database (Denmark)

    Li, Shuxia

    2015-01-01

    the risk of clinic diseases e.g. diabetes, atherosclerosis, stroke and cardiovascular disease. Metabolic phenotypes, similar to most complex traits, can be influenced by both genetic and environmental factors as well as their interplay. Many family and twin studies have demonstrated both genetic...... and environmental factors play important role in the variation of metabolic phenotypes and intra-individual change over time. Although both genetic and environmental factors are involved the development of metabolic disorders, the role of environment should be emphasized as the expression or function of gene can...... be regulated to adapt to existing environmental circumstance. In other words, adaptive evolution in populations under distinct environmental and cultural circumstances could have resulted in varying genetic basis of metabolic factors and development of metabolic disorders or diseases. Thus, it can...

  7. [Genetics factors in pathogenesis and clinical genetics of binge eating disorder].

    Science.gov (United States)

    Kibitov, А О; Мazo, G E

    2016-01-01

    Genetic studies have shown that binge eating disorder (ВЕD) aggregates in families, heritability was estimated as about 60% and additive genetic influences on BED up to 50%. Using a genetic approach has proved useful for verifying the diagnostic categories of BED using DSM-IV criteria and supporting the validity of considering this pathology as a separate nosological category. The results confirmed the genetic and pathogenic originality of BED as a separate psychopathological phenomenon, but not a subtype of obesity. It seems fruitful to considerate BED as a disease with hereditary predisposition with significant genetic influence and a complex psychopathological syndrome, including not only eating disorders, but also depressive and addictive component. A possible mechanism of pathogenesis of BED may be the interaction of the neuroendocrine and neurotransmitters systems including the active involvement of the reward system in response to a variety of chronic stress influences with the important modulatory role of specific personality traits. The high level of genetic influence on the certain clinical manifestations of BED confirms the ability to identify the subphenotypes of BED on genetic basis involving clinical criteria. It can not only contribute to further genetic studies, taking into account more homogeneous samples, but also help in finding differentiated therapeutic approaches.

  8. Genetic and Environmental Influences on Individual Differences in Frequency of Play with Pets among Middle-Aged Men: A Behavioral Genetic Analysis.

    Science.gov (United States)

    Jacobson, Kristen C; Hoffman, Christy L; Vasilopoulos, Terrie; Kremen, William S; Panizzon, Matthew S; Grant, Michael D; Lyons, Michael J; Xian, Hong; Franz, Carol E

    2012-12-01

    There is growing evidence that pet ownership and human-animal interaction (HAI) have benefits for human physical and psychological well-being. However, there may be pre-existing characteristics related to patterns of pet ownership and interactions with pets that could potentially bias results of research on HAI. The present study uses a behavioral genetic design to estimate the degree to which genetic and environmental factors contribute to individual differences in frequency of play with pets among adult men. Participants were from the ongoing longitudinal Vietnam Era Twin Study of Aging (VETSA), a population-based sample of 1,237 monozygotic (MZ) and dizygotic (DZ) twins aged 51-60 years. Results demonstrate that MZ twins have higher correlations than DZ twins on frequency of pet play, suggesting that genetic factors play a role in individual differences in interactions with pets. Structural equation modeling revealed that, according to the best model, genetic factors accounted for as much as 37% of the variance in pet play, although the majority of variance (63-71%) was due to environmental factors that are unique to each twin. Shared environmental factors, which would include childhood exposure to pets, overall accounted for influenced characteristics.

  9. Environmental enrichment imparts disease-modifying and transgenerational effects on genetically-determined epilepsy and anxiety.

    Science.gov (United States)

    Dezsi, Gabi; Ozturk, Ezgi; Salzberg, Michael R; Morris, Margaret; O'Brien, Terence J; Jones, Nigel C

    2016-09-01

    The absence epilepsies are presumed to be caused by genetic factors, but the influence of environmental exposures on epilepsy development and severity, and whether this influence is transmitted to subsequent generations, is not well known. We assessed the effects of environmental enrichment on epilepsy and anxiety outcomes in multiple generations of GAERS - a genetic rat model of absence epilepsy that manifests comorbid elevated anxiety-like behaviour. GAERS were exposed to environmental enrichment or standard housing beginning either prior to, or after epilepsy onset, and underwent EEG recordings and anxiety testing. Then, we exposed male GAERS to early enrichment or standard housing and generated F1 progeny, which also underwent EEG recordings. Hippocampal CRH mRNA expression and DNA methylation were assessed using RT-PCR and pyrosequencing, respectively. Early environmental enrichment delayed the onset of epilepsy in GAERS, and resulted in fewer seizures in adulthood, compared with standard housed GAERS. Enrichment also reduced the frequency of seizures when initiated in adulthood. Anxiety levels were reduced by enrichment, and these anti-epileptogenic and anxiolytic effects were heritable into the next generation. We also found reduced expression of CRH mRNA in GAERS exposed to enrichment, but this was not due to changes in DNA methylation. Environmental enrichment produces disease-modifying effects on genetically determined absence epilepsy and anxiety, and these beneficial effects are transferable to the subsequent generation. Reduced CRH expression was associated with these phenotypic improvements. Environmental stimulation holds promise as a naturalistic therapy for genetically determined epilepsy which may benefit subsequent generations. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Forjaz, C.L.M.; Bartholomeu, T. [Laboratório de Hemodinâmica da Atividade Motora (LAHAM), Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo, SP (Brazil); Rezende, J.A.S. [Escola Superior de Educação Física de Muzambinho, Muzambinho, MG (Brazil); Oliveira, J.A.; Basso, L.; Tani, G. [Laboratório de Comportamento Motor (LACOM), Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo, SP (Brazil); Prista, A. [Faculdade de Educação Física e Desporto, Universidade Pedagógica, Maputo (Mozambique); Maia, J.A.R. [CIFI2D, Laboratório de Cineantropometria e Gabinete de Estatística Aplicada, Faculdade de Desporto, Universidade do Porto, Porto (Portugal)

    2012-09-07

    Blood pressure (BP) and physical activity (PA) levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years) and their 82 fathers and 122 mothers (24 to 65 years) were evaluated. BP was measured, and total PA (TPA) was assessed by an interview (commuting, occupational, leisure time, and school time PA). Quantitative genetic modeling was used to estimate maximal heritability (h{sup 2}), and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h{sup 2} = 0.37 ± 0.10, P < 0.05; diastolic BP: h{sup 2} = 0.39 ± 0.09, P < 0.05; TPA: h{sup 2} = 0.24 ± 0.09, P < 0.05). Significant genetic (r{sub g}) and environmental (r{sub e}) correlations were detected between systolic and diastolic BP (r{sub g} = 0.67 ± 0.12 and r{sub e} = 0.48 ± 0.08, P < 0.05). Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r{sub e} = -0.18 ± 0.09, P = 0.057). In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences.

  11. Genetic and environmental influences on blood pressure and physical activity: a study of nuclear families from Muzambinho, Brazil

    Directory of Open Access Journals (Sweden)

    C.L.M. Forjaz

    2012-12-01

    Full Text Available Blood pressure (BP and physical activity (PA levels are inversely associated. Since genetic factors account for the observed variation in each of these traits, it is possible that part of their association may be related to common genetic and/or environmental influences. Thus, this study was designed to estimate the genetic and environmental correlations of BP and PA phenotypes in nuclear families from Muzambinho, Brazil. Families including 236 offspring (6 to 24 years and their 82 fathers and 122 mothers (24 to 65 years were evaluated. BP was measured, and total PA (TPA was assessed by an interview (commuting, occupational, leisure time, and school time PA. Quantitative genetic modeling was used to estimate maximal heritability (h², and genetic and environmental correlations. Heritability was significant for all phenotypes (systolic BP: h² = 0.37 ± 0.10, P < 0.05; diastolic BP: h² = 0.39 ± 0.09, P < 0.05; TPA: h² = 0.24 ± 0.09, P < 0.05. Significant genetic (r g and environmental (r e correlations were detected between systolic and diastolic BP (r g = 0.67 ± 0.12 and r e = 0.48 ± 0.08, P < 0.05. Genetic correlations between BP and TPA were not significant, while a tendency to an environmental cross-trait correlation was found between diastolic BP and TPA (r e = -0.18 ± 0.09, P = 0.057. In conclusion, BP and PA are under genetic influences. Systolic and diastolic BP share common genes and environmental influences. Diastolic BP and TPA are probably under similar environmental influences.

  12. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    P.J. Basso

    2014-09-01

    Full Text Available Inflammatory bowel disease (IBD, which includes Crohn's disease (CD and ulcerative colitis (UC, is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

  13. [Breast cancer genetics. BRCA1 and BRCA2: the main genes for disease predisposition].

    Science.gov (United States)

    Ruiz-Flores, P; Calderón-Garcidueñas, A L; Barrera-Saldaña, H A

    2001-01-01

    Breast cancer is among the most common world cancers. In Mexico this neoplasm has been progressively increasing since 1990 and is expected to continue. The risk factors for this disease are age, some reproductive factors, ionizing radiation, contraceptives, obesity and high fat diets, among other factors. The main risk factor for BC is a positive family history. Several families, in which clustering but no mendelian inheritance exists, the BC is due probably to mutations in low penetrance genes and/or environmental factors. In families with autosomal dominant trait, the BRCA1 and BRCA2 genes are frequently mutated. These genes are the two main BC susceptibility genes. BRCA1 predispose to BC and ovarian cancer, while BRCA2 mutations predispose to BC in men and women. Both are long genes, tumor suppressors, functioning in a cell cycle dependent manner, and it is believed that both switch on the transcription of several genes, and participate in DNA repair. The mutations profile of these genes is known in developed countries, while in Latin America their search has just began. A multidisciplinary group most be responsible of the clinical management of patients with mutations in BRCA1 and BRCA2, and the risk assignment and Genetic counseling most be done carefully.

  14. Does cortisol moderate the environmental association between peer victimization and depression symptoms? A genetically informed twin study.

    Science.gov (United States)

    Brendgen, Mara; Ouellet-Morin, Isabelle; Lupien, Sonia; Vitaro, Frank; Dionne, Ginette; Boivin, Michel

    2017-10-01

    Many youths who are victimized by peers suffer from depression symptoms. However, not all bullying victims show depression symptoms and individuals' biological sensitivity may play an important moderating role in this regard. In line with this notion, peer victimization has been associated with increased depressive symptoms in youth with higher basal cortisol secretion. It is unclear, however, whether this moderating effect of cortisol really concerns the environmental effect of peer victimization on depression. Indeed, genetic factors can also influence individuals' environmental experiences, including peer victimization, and part of these genetic factors may be those associated with depression. Using a genetically informed design based on 159 monozygotic and 120 dizygotic twin pairs (52% girls) assessed at age 14 years, this study examined whether cortisol secretion moderates the environmental or the genetic association between peer victimization and depression symptoms. Salivary cortisol at awakening was obtained with buccal swabs during four school week days. Peer victimization and depression were assessed via self-reports. Cholesky modeling revealed that peer victimization was associated with depression symptoms via both genetic and environmental pathways. Moreover, the environmental association between peer victimization and depression symptoms steadily increased with increasing levels of morning cortisol. The genetic association between peer victimization and depression symptoms also varied, albeit less, as a function of individuals' cortisol secretion. These findings support the hypothesis that peer victimization increases internalizing psychopathology mainly in youth with heightened biological reactivity to environmental conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Identification of Germline Genetic Mutations in Pancreatic Cancer Patients

    Science.gov (United States)

    Salo-Mullen, Erin E.; O’Reilly, Eileen; Kelsen, David; Ashraf, Asad M.; Lowery, Maeve; Yu, Kenneth; Reidy, Diane; Epstein, Andrew S.; Lincoln, Anne; Saldia, Amethyst; Jacobs, Lauren M.; Rau-Murthy, Rohini; Zhang, Liying; Kurtz, Robert; Saltz, Leonard; Offit, Kenneth; Robson, Mark; Stadler, Zsofia K.

    2016-01-01

    Background Pancreatic adenocarcinoma (PAC) is part of several cancer predisposition syndromes; however, indications for genetic counseling/testing are not well-defined. We sought to determine mutation prevalence and characteristics that predict for inherited predisposition to PAC. Methods We identified 175 consecutive PAC patients who underwent clinical genetics assessment at Memorial Sloan Kettering between 2011–2014. Clinical data, family history, and germline results were evaluated. Results Among 159 PAC patients who pursued genetic testing, 24 pathogenic mutations were identified (15.1%; 95%CI, 9.5%–20.7%), including BRCA2(n=13), BRCA1(n=4), p16(n=2), PALB2(n=1), and Lynch syndrome(n=4). BRCA1/BRCA2 prevalence was 13.7% in Ashkenazi Jewish(AJ) (n=95) and 7.1% in non-AJ(n=56) patients. In AJ patients with strong, weak, or absent family history of BRCA-associated cancers, mutation prevalence was 16.7%, 15.8%, and 7.4%, respectively. Mean age at diagnosis in all mutation carriers was 58.5y(range 45–75y) compared to 64y(range 27–87y) in non-mutation carriers(P=0.02). Although BRCA2 was the most common mutation identified, no patients with early-onset PAC(≤50y) harbored a BRCA2 mutation and the mean age at diagnosis in BRCA2 carriers was equivalent to non-mutation carriers(P=0.34). Mutation prevalence in early-onset patients(n=21) was 28.6%, including BRCA1(n=2), p16(n=2), MSH2(n=1) and MLH1(n=1). Conclusion Mutations in BRCA2 account for over 50% of PAC patients with an identified susceptibility syndrome. AJ patients had high BRCA1/BRCA2 prevalence regardless of personal/family history, suggesting that ancestry alone indicates a need for genetic evaluation. With the exception of BRCA2-associated PAC, inherited predisposition to PAC is associated with earlier age at PAC diagnosis suggesting that this subset of patients may also represent a population warranting further evaluation. PMID:26440929

  16. Genetic and environmental-genetic interaction rules for the myopia based on a family exposed to risk from a myopic environment.

    Science.gov (United States)

    Wenbo, Li; Congxia, Bai; Hui, Liu

    2017-08-30

    To quantitatively assess the role of heredity and environmental factors in myopia based on the family with enough exposed to risk from myopic environment for establishment of environmental and genetic index (EGI). A pedigree analysis unit was defined as one child (university student), father, and mother. Information pertaining to visual acuity, experience in participating in the college entrance examination in mainland of China (regarded as a strong environmental risk for myopia), and occupation for pedigree analysis units were obtained. The difference between effect of both genetic and environmental factors (myopia prevalence in children with two myopic parents) and environmental factors (myopia prevalence in children of whom neither parent was myopic) was defined as the EGI. Multiple regression analysis was performed for 114 pedigree using diopters of father, mother, average diopters in parents, maximum and minimum diopters in father and mother as variables. A total of 353 farmers and 162 farmer families were used as a control group. A distinct difference in myopia rate (96.2% versus 57.7%) was observed for children from parents with myopia and parents without myopia (EGI=0.385). The maximum diopter was included to regression equation which was statistically significant. The prevalence of myopia was 9.9% in the farmer. The prevalence in children is similar between the farmer and other families. A new genetic rule that myopia in children was directly related with maximum diopters in father and mother may be suggested. Environmental factors may play a leading role in the formation of myopia. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chia-Hsuan Chou

    Full Text Available Oral squamous cell carcinoma (OSCC is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively. AURKA, which encodes a centrosome-related serine/threonine kinase, is frequently amplified and overexpressed in many human cancers, particularly advanced OSCC. We conducted a hospital-based case-control study to estimate AURKA single-nucleotide polymorphisms (SNPs and environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics.We enrolled a total of 876 OSCC patients and 1200 controls. Four SNPs of AURKA, namely rs1047972, rs2273535, rs2064863, and rs6024836, were analyzed using real-time polymerase chain reaction (PCR. Among the 1420 smokers, the AURKA polymorphism carriers with the betel nut chewing habit had a higher risk of oral cancer than AURKA wild-type (WT carriers without the betel nut chewing habit. Patients with the AURKA rs2064863 gene had a 1.365-fold higher risk of stage III or IV OSCC (95% confidence interval [CI] 1.029-1.811 than those with the rs2064863 WT gene. Furthermore, carriers of the AURKA rs1047972/rs2273535/rs2064863 C-A-T haplotype had a 1.736-fold (95% CI 1.110-2.715 higher risk of OSCC than controls (C-T-T, the most common haplotype. Among patients with the betel quid chewing habit, carriers of other haplotypes (C-T-T, C-A-G, T-A-T, T-A-G, T-T-T, and C-T-G had a 12.857-fold (95% CI 10.731-15.404 increased risk, and carriers of the C-A-T haplotype had the highest risk (AOR: 31.120; 95% CI 13.864-69.850 of OSCC, compared with those without the betel quid chewing who harbored other haplotypes.In conclusion, betel nut chewing combined with the AURKA C-A-T haplotypes lead to a high risk of OSCC. These findings reveal a novel genetic-environmental predisposition for oral tumorigenesis.

  18. Genetic and environmental influences on female sexual orientation, childhood gender typicality and adult gender identity.

    Directory of Open Access Journals (Sweden)

    Andrea Burri

    Full Text Available BACKGROUND: Human sexual orientation is influenced by genetic and non-shared environmental factors as are two important psychological correlates--childhood gender typicality (CGT and adult gender identity (AGI. However, researchers have been unable to resolve the genetic and non-genetic components that contribute to the covariation between these traits, particularly in women. METHODOLOGY/PRINCIPAL FINDINGS: Here we performed a multivariate genetic analysis in a large sample of British female twins (N = 4,426 who completed a questionnaire assessing sexual attraction, CGT and AGI. Univariate genetic models indicated modest genetic influences on sexual attraction (25%, AGI (11% and CGT (31%. For the multivariate analyses, a common pathway model best fitted the data. CONCLUSIONS/SIGNIFICANCE: This indicated that a single latent variable influenced by a genetic component and common non-shared environmental component explained the association between the three traits but there was substantial measurement error. These findings highlight common developmental factors affecting differences in sexual orientation.

  19. Nature, Genetics and the Biophilia Connection: Exploring Linkages with Social Work Values and Practice

    Directory of Open Access Journals (Sweden)

    Fred H. Besthorn

    2003-05-01

    Full Text Available Social work’s notion of environment and its environmental responsibilities has always been narrowly defined. The profession has tended to either neglect natural environmental issues or accept shallow, ecological conceptualizations of nature as something other, quite separate from the human enterprise and/or outside the reach of social work activity. The Biophilia Hypothesis, first articulated by Harvard biologist E.O.Wilson in 1984, offers social work as a fundamentally different view of the person/environment construct and argues for a primary shift in the way the profession views its relationship with the natural world. This article traces the conceptual development of the Biophilic theory and reviews pivotal empirical evidence explicitly arguing for the essential Biophilic premise that humans have acquired, through their long evolutionary history, a strong genetic predisposition for nature and natural settings. It offers key insights and examples for incorporating Biophilia into social work’s values and knowledge base and how it may impact the profession’s practice strategies and techniques.

  20. Internet addiction and its facets: The role of genetics and the relation to self-directedness.

    Science.gov (United States)

    Hahn, Elisabeth; Reuter, Martin; Spinath, Frank M; Montag, Christian

    2017-02-01

    A growing body of research focuses on problematic behavior patterns related to the use of the Internet to identify contextual as well as individual risk factors of this new phenomenon called Internet addiction (IA). IA can be described as a multidimensional syndrome comprising aspects such as craving, development of tolerance, loss of control and negative consequences. Given that previous research on other addictive behaviors showed substantial heritability, it can be expected that the vulnerability to IA may also be due to a person's genetic predisposition. However, it is questionable whether distinct components of IA have different etiologies. Using data from a sample of adult monozygotic and dizygotic twins and non-twin siblings (N=784 individuals, N=355 complete pairs, M=30.30years), we investigated the magnitude of genetic and environmental influences on generalized IA as well as on specific facets such as excessive use, self-regulation, preference for online social interaction or negative consequences. To explain the heritability in IA, we further examined the relation to Self-Directedness as potential mediating source. Results showed that relative contributions of genetic influences vary considerable for different components of IA. For generalized IA factors, individual differences could be explained by shared and non-shared environmental influences while genetic influences did not play a role. For specific facets of IA and private Internet use in hours per week, heritability estimates ranged between 21% and 44%. Bivariate analysis indicated that Self-Directedness accounted for 20% to 65% of the genetic variance in specific IA facets through overlapping genetic pathways. Implications for future research are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Human fertility, molecular genetics, and natural selection in modern societies.

    Directory of Open Access Journals (Sweden)

    Felix C Tropf

    Full Text Available Research on genetic influences on human fertility outcomes such as number of children ever born (NEB or the age at first childbirth (AFB has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758, results show significant additive genetic effects on both traits explaining 10% (SE = 5 of the variance in the NEB and 15% (SE = 4 in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of -0.62 (SE = 0.27, p-value = 0.02. This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size.

  2. Genetic and environmental multidimensionality of well- and ill-being in middle aged twin men.

    Science.gov (United States)

    Franz, Carol E; Panizzon, Matthew S; Eaves, Lindon J; Thompson, Wesley; Lyons, Michael J; Jacobson, Kristen C; Tsuang, Ming; Glatt, Stephen J; Kremen, William S

    2012-07-01

    The goals of the study were to determine the extent to which the underlying structure of different types of well-being was multidimensional and whether well- and ill-being were influenced by similar or different genetic and environmental factors. Participants were 1226 male twins ages 51-60, from the Vietnam Era Twin Study of Aging. Measures included: psychological well-being, Multidimensional Personality Questionnaire Well-Being scale (MPQWB), life satisfaction, self-esteem, and depressive symptoms. A two-orthogonal-factor common pathway model fit the data well. Psychological well-being and self-esteem loaded most strongly on Factor 1, which was highly heritable (h(2) = .79). Life satisfaction loaded most strongly on Factor 2, which was only moderately heritable (h(2) = .32). Only MPQWB had measure-specific genetic influences. Depressive symptoms loaded on both factors, and only depressive symptoms had measure-specific common environmental influences. All measures had specific unique environmental influences. Results indicate that well-being is genetically and environmentally multidimensional and that ill-being has partial overlap with both latent factors.

  3. International Szent-Györgyi Prize for Progress in Cancer Research: basic and translational research recognition : Mary-Claire King received the 2016 Prize for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer.

    Science.gov (United States)

    Hartmann, Hali; Zhao, Jie; Ba, Sujuan

    2017-11-21

    The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award sponsored by the National Foundation for Cancer Research (NFCR)-a leading cancer research charitable organization in the United States that supports innovative cancer research globally with the ultimate goal to cure cancer. The coveted Szent-Györgyi Prize annually honors a scientist whose seminal discovery or body of work has resulted in, or led toward, notable contributions to cancer prevention, diagnosis, or treatment; and the discovery has had a high direct impact of saving people's lives. In addition, the prize promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. In 2016, NFCR's Szent-Györgyi Prize Selection Committee was unanimous in its decision to recognize an icon in human disease genetics, Dr. Mary-Claire King, for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer. Her proof of existence of BRCA1 gene and its location has made genetic screening for breast and ovarian cancers possible, saving lives of many people who are at high risk with inherited BRCA1 mutations.

  4. Prepubertal Ovariectomy Exaggerates Adult Affective Behaviors and Alters the Hippocampal Transcriptome in a Genetic Rat Model of Depression

    Directory of Open Access Journals (Sweden)

    Neha S. Raghavan

    2018-01-01

    Full Text Available Major depressive disorder (MDD is a debilitating illness that affects twice as many women than men postpuberty. This female bias is thought to be caused by greater heritability of MDD in women and increased vulnerability induced by female sex hormones. We tested this hypothesis by removing the ovaries from prepubertal Wistar Kyoto (WKY more immobile (WMI females, a genetic animal model of depression, and its genetically close control, the WKY less immobile (WLI. In adulthood, prepubertally ovariectomized (PrePubOVX animals and their Sham-operated controls were tested for depression- and anxiety-like behaviors, using the routinely employed forced swim and open field tests, respectively, and RNA-sequencing was performed on their hippocampal RNA. Our results confirmed that the behavioral and hippocampal expression changes that occur after prepubertal ovariectomy are the consequences of an interaction between genetic predisposition to depressive behavior and ovarian hormone-regulated processes. Lack of ovarian hormones during and after puberty in the WLIs led to increased depression-like behavior. In WMIs, both depression- and anxiety-like behaviors worsened by prepubertal ovariectomy. The unbiased exploration of the hippocampal transcriptome identified sets of differentially expressed genes (DEGs between the strains and treatment groups. The relatively small number of hippocampal DEGs resulting from the genetic differences between the strains confirmed the genetic relatedness of these strains. Nevertheless, the differences in DEGs between the strains in response to prepubertal ovariectomy identified different molecular processes, including the importance of glucocorticoid receptor-mediated mechanisms, that may be causative of the increased depression-like behavior in the presence or absence of genetic predisposition. This study contributes to the understanding of hormonal maturation-induced changes in affective behaviors and the hippocampal

  5. Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence.

    Science.gov (United States)

    Kendler, Kenneth S; Myers, John; Prescott, Carol A

    2007-11-01

    Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence

  6. Genetic and environmental factors interact to influence anxiety.

    Science.gov (United States)

    Gross, Cornelius; Hen, René

    2004-01-01

    Both genetic and environmental factors influence normal anxiety traits as well as anxiety disorders. In addition it is becoming increasingly clear that these factors interact to produce specific anxiety-related behaviors. For example, in humans and in monkeys mutations in the gene encoding for the serotonin transporter result in increased anxiety in adult life when combined with a stressful environment during development. Another recent example comes from twin studies suggesting that a small hippocampus can be a predisposing condition that renders individuals susceptible to post traumatic stress disorder. Such examples illustrate how specific mutations leading to abnormal brain development may increase vulnerability to environmental insults which may in turn lead to specific anxiety disorders.

  7. A genetic basis for functional hypothalamic amenorrhea.

    OpenAIRE

    Caronia, L.M.; Martin, C.; Welt, C.K.; Sykiotis, G.P.; Quinton, R.; Thambundit, A.; Avbelj, M.; Dhruvakumar, S.; Plummer, L.; Hughes, V.A.; Seminara, S.B.; Boepple, P.A.; Sidis, Y.; Crowley, W.F.; Martin, K.A.

    2011-01-01

    Background: Functional hypothalamic amenorrhea is a reversible form of gonadotropin-releasing hormone (GnRH) deficiency commonly triggered by stressors such as excessive exercise, nutritional deficits, or psychological distress. Women vary in their susceptibility to inhibition of the reproductive axis by such stressors, but it is unknown whether this variability reflects a genetic predisposition to hypothalamic amenorrhea. We hypothesized that mutations in genes involved in idiopathic hypogon...

  8. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Maehlen, Marthe T.; Olsen, Inge C.; Andreassen, Bettina K.; Viken, Marte K.; Jiang, Xia; Alfredsson, Lars; Kallberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina; Toes, Rene; Zhernakova, Alexandra; Gutierrez-Achury, Javier; de Bakker, Paul I. W.; Martin, Javier; Teruel, Maria; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore K.; Lie, Benedicte A.

    Objective Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number

  9. Genetic risk scores and number of autoantibodies in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Maehlen, Marthe T; Olsen, Inge C; Andreassen, Bettina K; Viken, Marte K; Jiang, Xia; Alfredsson, Lars; Källberg, Henrik; Brynedal, Boel; Kurreeman, Fina; Daha, Nina; Toes, Rene; Zhernakova, Alexandra; Gutierrez-Achury, Javier; de Bakker, Paul I W; Martin, Javier; Teruel, María; Gonzalez-Gay, Miguel A; Rodríguez-Rodríguez, Luis; Balsa, Alejandro; Uhlig, Till; Kvien, Tore K; Lie, Benedicte A

    OBJECTIVE: Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number

  10. Genetic and environmental influences on thin-ideal internalization across puberty and preadolescent, adolescent, and young adult development.

    Science.gov (United States)

    Suisman, Jessica L; Thompson, J Kevin; Keel, Pamela K; Burt, S Alexandra; Neale, Michael; Boker, Steven; Sisk, Cheryl; Klump, Kelly L

    2014-11-01

    Mean-levels of thin-ideal internalization increase during adolescence and pubertal development, but it is unknown whether these phenotypic changes correspond to developmental changes in etiological (i.e., genetic and environmental) risk. Given the limited knowledge on risk for thin-ideal internalization, research is needed to guide the identification of specific types of risk factors during critical developmental periods. The present twin study examined genetic and environmental influences on thin-ideal internalization across adolescent and pubertal development. Participants were 1,064 female twins (ages 8-25 years) from the Michigan State University Twin Registry. Thin-ideal internalization and pubertal development were assessed using self-report questionnaires. Twin moderation models were used to examine if age and/or pubertal development moderate genetic and environmental influences on thin-ideal internalization. Phenotypic analyses indicated significant increases in thin-ideal internalization across age and pubertal development. Twin models suggested no significant differences in etiologic effects across development. Nonshared environmental influences were most important in the etiology of thin-ideal internalization, with genetic, shared environmental, and nonshared environmental accounting for approximately 8%, 15%, and 72%, respectively, of the total variance. Despite mean-level increases in thin-ideal internalization across development, the relative influence of genetic versus environmental risk did not differ significantly across age or pubertal groups. The majority of variance in thin-ideal internalization was accounted for by environmental factors, suggesting that mean-level increases in thin-ideal internalization may reflect increases in the magnitude/strength of environmental risk across this period. Replication is needed, particularly with longitudinal designs that assess thin-ideal internalization across key developmental phases. © 2014 Wiley

  11. Investigating genetic and environmental contributions to adolescent externalizing behavior in a collectivistic culture: a multi-informant twin study.

    Science.gov (United States)

    Chen, J; Yu, J; Zhang, J; Li, X; McGue, M

    2015-07-01

    Little is known about the etiology of adolescents' externalizing behavior (Ext) in collectivistic cultures. We aimed to fill this gap by investigating the genetic and environmental influences on Ext in Chinese adolescents. The etiological heterogeneity of aggression (AGG) and rule breaking (RB) was also examined. The study sample included 908 pairs of same-sex twins aged from 10 to 18 years (mean = 13.53 years, s.d. = 2.26). Adolescents' Ext were assessed with the Achenbach System of Empirically Based Assessment including Child Behavior Checklist, Teacher Report Form, and Youth Self-Report. Univariate genetic analyses showed that genetic influences on all measures were moderate ranging from 34% to 50%, non-shared environmental effects ranged from 23% to 52%, and shared environmental effects were significant in parent- and teacher-reported measures ranging from 29% to 43%. Bivariate genetic analyses indicated that AGG and RB shared large genetic influences (r g = 0.64-0.79) but moderate non-shared environmental factors (r e = 0.34-0.52). Chinese adolescents' Ext was moderately influenced by genetic factors. AGG and RB had moderate independent genetic and non-shared environmental influences, and thus constitute etiologically distinct dimensions within Ext in Chinese adolescents. The heritability of AGG, in particular, was smaller in Chinese adolescents than suggested by previous data obtained on Western peers. This study suggests that the collectivistic cultural values and Confucianism philosophy may attenuate genetic potential in Ext, especially AGG.

  12. Persistence and innovation effects in genetic and environmental factors in negative emotionality during infancy: A twin study.

    Directory of Open Access Journals (Sweden)

    Lyndall Schumann

    Full Text Available Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age.Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus.There were substantial and similar heritability (approximately 31% and shared environmental (57.3% contributions to negative emotionality at both 5 and 18 months. The trait's interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months.In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology.

  13. Overlapping genetic and environmental influences among men's alcohol consumption and problems, romantic quality and social support.

    Science.gov (United States)

    Salvatore, J E; Prom-Wormley, E; Prescott, C A; Kendler, K S

    2015-08-01

    Alcohol consumption and problems are associated with interpersonal difficulties. We used a twin design to assess in men the degree to which genetic or environmental influences contributed to the covariance between alcohol consumption and problems, romantic quality and social support. The sample included adult male-male twin pairs (697 monozygotic and 487 dizygotic) for whom there were interview-based data on: alcohol consumption (average monthly alcohol consumption in the past year); alcohol problems (lifetime alcohol dependence symptoms); romantic conflict and warmth; friend problems and support; and relative problems and support. Key findings were that genetic and unique environmental factors contributed to the covariance between alcohol consumption and romantic conflict; genetic factors contributed to the covariance between alcohol problems and romantic conflict; and common and unique environmental factors contributed to the covariance between alcohol problems and friend problems. Recognizing and addressing the overlapping genetic and environmental influences that alcohol consumption and problems share with romantic quality and other indicators of social support may have implications for substance use prevention and intervention efforts.

  14. Externalizing problems in childhood and adolescence predict subsequent educational achievement but for different genetic and environmental reasons.

    Science.gov (United States)

    Lewis, Gary J; Asbury, Kathryn; Plomin, Robert

    2017-03-01

    Childhood behavior problems predict subsequent educational achievement; however, little research has examined the etiology of these links using a longitudinal twin design. Moreover, it is unknown whether genetic and environmental innovations provide incremental prediction for educational achievement from childhood to adolescence. We examined genetic and environmental influences on parental ratings of behavior problems across childhood (age 4) and adolescence (ages 12 and 16) as predictors of educational achievement at age 16 using a longitudinal classical twin design. Shared-environmental influences on anxiety, conduct problems, and peer problems at age 4 predicted educational achievement at age 16. Genetic influences on the externalizing behaviors of conduct problems and hyperactivity at age 4 predicted educational achievement at age 16. Moreover, novel genetic and (to a lesser extent) nonshared-environmental influences acting on conduct problems and hyperactivity emerged at ages 12 and 16, adding to the genetic prediction from age 4. These findings demonstrate that genetic and shared-environmental factors underpinning behavior problems in early childhood predict educational achievement in midadolescence. These findings are consistent with the notion that early-childhood behavior problems reflect the initiation of a life-course persistent trajectory with concomitant implications for social attainment. However, we also find evidence that genetic and nonshared-environment innovations acting on behavior problems have implications for subsequent educational achievement, consistent with recent work arguing that adolescence represents a sensitive period for socioaffective development. © 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

  15. Genetic Structure of Bluefin Tuna in the Mediterranean Sea Correlates with Environmental Variables

    Science.gov (United States)

    Riccioni, Giulia; Stagioni, Marco; Landi, Monica; Ferrara, Giorgia; Barbujani, Guido; Tinti, Fausto

    2013-01-01

    Background Atlantic Bluefin Tuna (ABFT) shows complex demography and ecological variation in the Mediterranean Sea. Genetic surveys have detected significant, although weak, signals of population structuring; catch series analyses and tagging programs identified complex ABFT spatial dynamics and migration patterns. Here, we tested the hypothesis that the genetic structure of the ABFT in the Mediterranean is correlated with mean surface temperature and salinity. Methodology We used six samples collected from Western and Central Mediterranean integrated with a new sample collected from the recently identified easternmost reproductive area of Levantine Sea. To assess population structure in the Mediterranean we used a multidisciplinary framework combining classical population genetics, spatial and Bayesian clustering methods and a multivariate approach based on factor analysis. Conclusions FST analysis and Bayesian clustering methods detected several subpopulations in the Mediterranean, a result also supported by multivariate analyses. In addition, we identified significant correlations of genetic diversity with mean salinity and surface temperature values revealing that ABFT is genetically structured along two environmental gradients. These results suggest that a preference for some spawning habitat conditions could contribute to shape ABFT genetic structuring in the Mediterranean. However, further studies should be performed to assess to what extent ABFT spawning behaviour in the Mediterranean Sea can be affected by environmental variation. PMID:24260341

  16. Socioeconomic Status Moderates Genetic and Environmental Effects on the Amount of Alcohol Use

    Science.gov (United States)

    Hamdi, Nayla R; Krueger, Robert F.; South, Susan C.

    2015-01-01

    Background Much is unknown about the relationship between socioeconomic status (SES) and alcohol use, including the means by which SES may influence risk for alcohol use. Methods Using a sample of 672 twin pairs (aged 25–74) derived from the MacArthur Foundation Survey of Midlife Development in the United States (MIDUS), the present study examined whether SES, measured by household income and educational attainment, moderates genetic and environmental influences on three indices of alcohol use: amount used, frequency of use, and problem use. Results We found significant moderation for amount of alcohol used. Specifically, genetic effects were greater in low-SES conditions, shared environmental effects (i.e., environmental effects that enhance the similarity of twins from the same families) tended to increase in high-SES conditions, and non-shared environmental effects (i.e., environmental effects that distinguish twins) tended to decrease with SES. This pattern of results was found for both income and education, and it largely replicated at a second wave of assessment spaced nine years after the first. There was virtually no evidence of moderation for either frequency of alcohol use or alcohol problems. Conclusions Our findings indicate that genetic and environmental influences on drinking amount vary as a function of the broader SES context, whereas the etiologies of other drinking phenomena are less affected by this context. Efforts to find the causes underlying the amount of alcohol used are likely to be more successful if such contextual information is taken into account. PMID:25778493

  17. Socioeconomic status moderates genetic and environmental effects on the amount of alcohol use.

    Science.gov (United States)

    Hamdi, Nayla R; Krueger, Robert F; South, Susan C

    2015-04-01

    Much is unknown about the relationship between socioeconomic status (SES) and alcohol use, including the means by which SES may influence risk for alcohol use. Using a sample of 672 twin pairs (aged 25 to 74) derived from the MacArthur Foundation Survey of Midlife Development in the United States, this study examined whether SES, measured by household income and educational attainment, moderates genetic and environmental influences on 3 indices of alcohol use: amount used, frequency of use, and problem use. We found significant moderation for amount of alcohol used. Specifically, genetic effects were greater in low-SES conditions, shared environmental effects (i.e., environmental effects that enhance the similarity of twins from the same families) tended to increase in high-SES conditions, and nonshared environmental effects (i.e., environmental effects that distinguish twins) tended to decrease with SES. This pattern of results was found for both income and education, and it largely replicated at a second wave of assessment spaced 9 years after the first. There was virtually no evidence of moderation for either frequency of alcohol use or alcohol problems. Our findings indicate that genetic and environmental influences on drinking amount vary as a function of the broader SES context, whereas the etiologies of other drinking phenomena are less affected by this context. Efforts to find the causes underlying the amount of alcohol used are likely to be more successful if such contextual information is taken into account. Copyright © 2015 by the Research Society on Alcoholism.

  18. Genetic and Environmental Basis in Phenotype Correlation Between Physical Function and Cognition in Aging Chinese Twins

    DEFF Research Database (Denmark)

    Xu, Chunsheng; Zhang, Dongfeng; Tian, Xiaocao

    2017-01-01

    for cognition with handgrip strength, FTSST, near visual acuity, and number of teeth lost. Cognitive function was genetically related to pulmonary function. The FTSST and cognition shared almost the same common environmental factors but only part of the unique environmental factors, both with negative......Although the correlation between cognition and physical function has been well studied in the general population, the genetic and environmental nature of the correlation has been rarely investigated. We conducted a classical twin analysis on cognitive and physical function, including forced...... and cognitive function. Bivariate analysis showed mildly positively genetic correlations between cognition and FEV1, r G = 0.23 [95% CI: 0.03, 0.62], as well as FVC, r G = 0.35 [95% CI: 0.06, 1.00]. We found that FTSST and cognition presented very high common environmental correlation, r C = -1.00 [95% CI: -1...

  19. Why do some like it hot? Genetic and environmental contributions to the pleasantness of oral pungency.

    Science.gov (United States)

    Törnwall, Outi; Silventoinen, Karri; Kaprio, Jaakko; Tuorila, Hely

    2012-10-10

    Although potential environmental influences on hedonic responses to oral pungency have been identified, little is known of the possible role of genetics underlying these responses. We explored the contribution of genetic and environmental influences on the pleasantness of oral pungency and spicy foods. Respondents were young adult Finnish twins (n=331, 21-25 years), including 47 complete monozygotic and 93 dizygotic twin pairs and 51 twin individuals without their co-twin. Pleasantness and intensity of strawberry jelly spiked with capsaicin (0.0001% w/v) relative to untainted strawberry jelly were rated. Furthermore, pleasantness of spicy foods and oral pungency caused by spices were rated based on food names in a questionnaire. Respondents were grouped as non-likers, medium-likers, and likers by their pleasantness responses to capsaicin spiked jelly. The contribution of genetic and environmental factors to variation and co-variation of the pleasantness traits was analyzed using quantitative genetic modeling. The non-likers perceived oral pungency as more intense (sensory) and rated pleasantness of spicy foods and pungent sensations caused by spices (questionnaire) as less pleasant than the likers. Genetic factors accounted for 18-58% of the variation in the pleasantness of oral pungency, spicy foods and pungent sensations. The rest was due to environmental factors. All pleasantness traits (sensory and questionnaire based) were shown to share a common genetic variance. This indicates that an underlying genetic aptitude to like oral pungency, and spicy foods exists and it is expressed in these measures. The findings broaden the understanding of the diverse nature of individual food preferences and motivate further search for the underlying genetic components of oral pungency. Copyright © 2012. Published by Elsevier Inc.

  20. Genetic and environmental influences on non-specific neck pain in early adolescence: A classical twin study

    Science.gov (United States)

    Ståhl, Minna K; El-Metwally, Ashraf A; Mikkelsson, Marja K; Salminen, Jouko J; Pulkkinen, Lea R; Rose, Richard J; Kaprio, Jaakko A

    2012-01-01

    Background Prevalence of neck pain has increased among adolescents. The origins of adult chronic neck pain may lie in late childhood, but for early prevention, more information is needed about its aetiology. We investigated the relative roles of genetic and environmental factors in early adolescent neck pain with a classic twin study. Methods Frequency of neck pain was assessed with a validated pain questionnaire in a population-based sample of nearly 1800 pairs of 11–12-year-old Finnish twins. Twin pair similarity for neck pain was quantified by polychoric correlations, and variance components were estimated with biometric structural equation modelling. Results Prevalence of neck pain reported at least once monthly was 38% and at least once weekly 16%, with no significant differences between gender or zygosity. A greater polychoric correlation in liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs (0.38), suggesting strong genetic influences. Model-fitting indicated that 68% (95% CI 62 to 74) of the variation in liability to neck pain could be attributed to genetic effects, with the remainder attributed to unshared environmental effects. No evidence for sex-specific genetic effects or for sex differences in the magnitude of genetic effects was found. Conclusions Genetic and unique environmental factors seem to play the most important roles in liability to neck pain in early adolescence. Future research should be directed to identifying pathways for genetic influences on neck pain and in exploring effectiveness of interventions that target already identified environmental risk factors. PMID:23139100

  1. Physical activity level of three generation families. Genetic and environmental factors

    Directory of Open Access Journals (Sweden)

    Raquel Nichele de Chaves

    2010-09-01

    Full Text Available This study aims (1 to investigate the presence of familial aggregation in physical activity (PA levels and sedentary behavior (SB among members of three generations families and (2 to estimate the magnitude of additive genetic influences on PA and SB phenotypes. The sample consisted of 100 extended families covering three generations (n=1034, from the Lisbon area, Portugal. Phenotypes were assessed via the short version of the self-administered International Physical Activity Questionnaire (IPAQ-SF. Measured phenotypes: total physical activity (TPA; vigorous (VPA; moderate (MPA; walking; time spent in sitting time (ST, watching television (WT and PA levels classification. Body mass index (BMI was calculated. Exploratory family analysis in all phenotypes was conducted in PEDSTATS software. The genetic component (h2 and shared environmental effect were estimated using maximum likelihood implemented in the SOLAR software package. All graphs were done in HLM software. Sex, age, sex*age, age2, sex*age2 and BMI were used as covariates. Significant level was set at 0,05. Genetic component estimates (h2 were as follows: TPA h2=0,28±0,06 (p<0.0001; VPA h2=0,35±0,06 (p<0.0001; MPA h2=0,29±0,06 (p<0.0001; walking h2=0,40±0,06 (p<0.0001; ST h2=0,29±0,06 (p<0.0001; WT h2=0,15±0,06 (p<0.003 and determination of the level physical activity h2=0,35±0,14 (p<0.007. Shared environmental effect was not significant. These results showed a low-to-moderate genetic contribution, between 15% to 40% of the total variability, in the PA and SB phenotypes. The genetic factors have low to moderate influence in this sample. Non-shared environmental factors appear to have the major contribution in these phenotypes.

  2. Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients

    DEFF Research Database (Denmark)

    Fagerudd, J A; Tarnow, L; Jacobsen, P

    1998-01-01

    Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN......+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion hypertension, defined as antihypertensive therapy or a 24-h ambulatory blood pressure (SpaceLabs 90207) > or = 135/85 mm...... for hypertension than were patients with DN+ and without parental treatment for hypertension (100 vs. 61%; P = 0.034; difference 39% [21-57%]). In conclusion, familial predisposition to essential hypertension increases the risk of diabetic nephropathy and may also contribute to the development of systemic...

  3. Predicting type 2 diabetes using genetic and environmental risk factors in a multi-ethnic Malaysian cohort.

    Science.gov (United States)

    Abdullah, N; Abdul Murad, N A; Mohd Haniff, E A; Syafruddin, S E; Attia, J; Oldmeadow, C; Kamaruddin, M A; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G

    2017-08-01

    Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation. This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project. The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R 2 and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. The models including environmental risk factors only had pseudo R 2 values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10 -4 -4.83 × 10 -12 ) and increased the pseudo R 2 by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 variation in Malaysian population groups. If gene-environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for

  4. Stroke genetics: prospects for personalized medicine

    Directory of Open Access Journals (Sweden)

    Markus Hugh S

    2012-09-01

    Full Text Available Abstract Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice.

  5. Celiac Disease Genomic, Environmental, Microbiome, and Metabolomic (CDGEMM Study Design: Approach to the Future of Personalized Prevention of Celiac Disease

    Directory of Open Access Journals (Sweden)

    Maureen M. Leonard

    2015-11-01

    Full Text Available In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD. Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.

  6. [Issues on business of genetic testing in near future].

    Science.gov (United States)

    Takada, Fumio

    2009-06-01

    Since 1990's, a business condition that company sells genetic testing services directly to consumers without through medical facility, so called "direct-to-consumers (DTC) genetic testing", has risen. They provide genetic testing for obesity, disease susceptibility or paternity, etc. There are serious problems in this kind of business. Most of the providers do not make sales with face-to-face selling, and do through internet instead. They do not provide genetic counseling by certified genetic counselor or clinical geneticist. Most DTC genetic testing services for disease susceptibility or predispositions including obesity, lack scientific validity, clinical validity and clinical utility. And also including paternity genetic testing, they all have risks of ethical legal and social issues (ELSI) in genetic discrimination and/or eugenics. The specific problem in Japan is that the healthcare section of the government still has not paid attention and not taken seriously the requirement to deploy safety net.

  7. Genetic, environmental, and epigenetic factors in the development of personality disturbance.

    Science.gov (United States)

    Depue, Richard A

    2009-01-01

    A dimensional model of personality disturbance is presented that is defined by extreme values on interacting subsets of seven major personality traits. Being at the extreme has marked effects on the threshold for eliciting those traits under stimulus conditions: that is, the extent to which the environment affects the neurobiological functioning underlying the traits. To explore the nature of development of extreme values on these traits, each trait is discussed in terms of three major issues: (a) the neurobiological variables associated with the trait, (b) individual variation in this neurobiology as a function of genetic polymorphisms, and (c) the effects of environmental adversity on these neurobiological variables through the action of epigenetic processes. It is noted that gene-environment interaction appears to be dependent on two main factors: (a) both genetic and environmental variables appear to have the most profound and enduring effects when they exert their effects during early postnatal periods, times when the forebrain is undergoing exuberant experience-expectant dendritic and axonal growth; and (b) environmental effects on neurobiology are strongly modified by individual differences in "traitlike" functioning of neurobiological variables. A model of the nature of the interaction between environmental and neurobiological variables in the development of personality disturbance is presented.

  8. Role of genetic in periodontal disease

    Directory of Open Access Journals (Sweden)

    Anand Narayanrao Wankhede

    2017-01-01

    Full Text Available Genetics is the study and understanding of the phenomena of heredity and variation. A large number of genes are associated with many systemic conditions. Periodontitis is inflammatory condition of periodontium. Periodontium consists of gingiva, periodontal ligament, cementum, and alveolar bone. It is considered being a multifactorial disease. Studies of animals and humans support the concept that a large number of genes' factor may be associated with periodontitis and clearly play a role in the predisposition and progression of periodontal diseases. It has been proven that genetic factors impair inflammatory and immune responses during periodontal diseases. Research on identifying specific genes causing periodontitis may improve and prevent the disease progression. The aim of this article is to focus on genetic risk factors and its influence for the various forms of periodontal disease.

  9. Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings.

    Science.gov (United States)

    Segal, N L; Feng, R; McGuire, S A; Allison, D B; Miller, S

    2009-01-01

    Earlier studies have established that a substantial percentage of variance in obesity-related phenotypes is explained by genetic components. However, only one study has used both virtual twins (VTs) and biological twins and was able to simultaneously estimate additive genetic, non-additive genetic, shared environmental and unshared environmental components in body mass index (BMI). Our current goal was to re-estimate four components of variance in BMI, applying a more rigorous model to biological and virtual multiples with additional data. Virtual multiples share the same family environment, offering unique opportunities to estimate common environmental influence on phenotypes that cannot be separated from the non-additive genetic component using only biological multiples. Data included 929 individuals from 164 monozygotic twin pairs, 156 dizygotic twin pairs, five triplet sets, one quadruplet set, 128 VT pairs, two virtual triplet sets and two virtual quadruplet sets. Virtual multiples consist of one biological child (or twins or triplets) plus one same-aged adoptee who are all raised together since infancy. We estimated the additive genetic, non-additive genetic, shared environmental and unshared random components in BMI using a linear mixed model. The analysis was adjusted for age, age(2), age(3), height, height(2), height(3), gender and race. Both non-additive genetic and common environmental contributions were significant in our model (P-valuesrole in BMI and that common environmental factors such as diet or exercise also affect BMI. This conclusion is consistent with our earlier study using a smaller sample and shows the utility of virtual multiples for separating non-additive genetic variance from common environmental variance.

  10. Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera.

    Science.gov (United States)

    Hirvonen, Elina A M; Pitkänen, Esa; Hemminki, Kari; Aaltonen, Lauri A; Kilpivaara, Outi

    2017-04-20

    Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients. The 12 shared variants (maximum allowed minor allele frequency  G (p.Phe418Leu) in ZXDC, c.1931C > G (p.Pro644Arg) in ATN1, and c.701G > A (p.Arg234Gln) in LRRC3. We also observed a rare, predicted benign germline variant c.2912C > G (p.Ala971Gly) in BCORL1 in all four patients. Somatic mutations in BCORL1 have been reported in myeloid malignancies. We further screened the variants in eight PV patients in six other Finnish families, but no other carriers were found. Exome sequencing provides a powerful tool for the identification of novel variants, and understanding the familial predisposition of diseases. This is the first report on Finnish familial PV cases, and we identified three novel candidate variants that may predispose to the disease.

  11. Nature and nurture: environmental influences on a genetic rat model of depression.

    Science.gov (United States)

    Mehta-Raghavan, N S; Wert, S L; Morley, C; Graf, E N; Redei, E E

    2016-03-29

    In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or 'nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, 'trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms.

  12. Genetic and environmental influences on infant growth: prospective analysis of the Gemini twin birth cohort.

    Directory of Open Access Journals (Sweden)

    Laura Johnson

    Full Text Available Infancy is a critical period during which rapid growth potentially programs future disease risk. Identifying the modifiable determinants of growth is therefore important. To capture the complexity of infant growth, we modeled growth trajectories from birth to six months in order to compare the genetic and environmental influences on growth trajectory parameters with single time-point measures at birth, three and six months of age.Data were from Gemini, a population sample of 2402 UK families with twins. An average 10 weight measurements per child made by health professionals were available over the first six months. Weights at birth, three and six months were identified. Longitudinal growth trajectories were modeled using SITAR utilizing all available weight measures for each child. SITAR generates three parameters: size (characterizing mean weight throughout infancy, tempo (indicating age at peak weight velocity (PWV, and velocity (reflecting the size of PWV. Genetic and environmental influences were estimated using quantitative genetic analysis.In line with previous studies, heritability of weight at birth and three months was low (38%, but it was higher at six months (62%. Heritability of the growth trajectory parameters was high for size (69% and velocity (57%, but low (35% for tempo. Common environmental influences predominated for tempo (42%.Modeled growth parameters using SITAR indicated that size and velocity were primarily under genetic influence but tempo was predominantly environmentally determined. These results emphasize the importance of identifying specific modifiable environmental determinants of the timing of peak infant growth.

  13. Genetic and environmental influences on self-reported reduced hearing in the old and oldest old

    DEFF Research Database (Denmark)

    Christensen, Kaare; Frederiksen, H; Hoffman, H J

    2001-01-01

    effects. Structural-equation analyses revealed a substantial heritability for self-reported reduced hearing of 40% (95% CI = 19-53%). The remaining variation could be attributed to individuals' nonfamilial environments. CONCLUSION: We found that genetic factors play an important role in self......-reported reduced hearing in both men and women age 70 and older. Because self-reports of reduced hearing involve misclassification, this estimate of the genetic influence on hearing disabilities is probably conservative. Hence, genetic and environmental factors play a substantial role in reduced hearing among......OBJECTIVES: The aim of the present twin study was to estimate the relative importance of genetic and environmental factors in variation in self-reported reduced hearing among the old and the oldest old. DESIGN: Self-reported hearing abilities of older twins assessed at intake interview...

  14. 75 FR 1585 - Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically...

    Science.gov (United States)

    2010-01-12

    ...] Draft Environmental Impact Statement; Determination of Regulated Status of Alfalfa Genetically... and Forage Genetics International alfalfa lines designated as events J101 and J163 as regulated... International (FGI) alfalfa events J101 and J163 were no longer considered regulated articles under the...

  15. Persistent Genetic and Family-Wide Environmental Contributions to Early Number Knowledge and Later Achievement in Mathematics.

    Science.gov (United States)

    Garon-Carrier, Gabrielle; Boivin, Michel; Kovas, Yulia; Feng, Bei; Brendgen, Mara; Vitaro, Frank; Séguin, Jean R; Tremblay, Richard E; Dionne, Ginette

    2017-12-01

    This study investigated the stable and transient genetic and environmental contributions to individual differences in number knowledge in the transition from preschool (age 5) to Grade 1 (age 7) and to the predictive association between early number knowledge and later math achievement (age 10-12). We conducted genetic simplex modeling across these three time points. Genetic variance was transmitted from preschool number knowledge to late-elementary math achievement; in addition, significant genetic innovation (i.e., new influence) occurred at ages 10 through 12 years. The shared and nonshared environmental contributions decreased during the transition from preschool to school entry, but shared and nonshared environment contributed to the continuity across time from preschool number knowledge to subsequent number knowledge and math achievement. There was no new environmental contribution at time points subsequent to preschool. Results are discussed in light of their practical implications for children who have difficulties with mathematics, as well as for preventive intervention.

  16. Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior.

    Science.gov (United States)

    Meier, Madeline H; Slutske, Wendy S; Heath, Andrew C; Martin, Nicholas G

    2011-05-01

    Sex differences in the genetic and environmental influences on childhood conduct disorder and adult antisocial behavior were examined in a large community sample of 6,383 adult male, female, and opposite-sex twins. Retrospective reports of childhood conduct disorder (prior to 18 years of age) were obtained when participants were approximately 30 years old, and lifetime reports of adult antisocial behavior (antisocial behavior after 17 years of age) were obtained 8 years later. Results revealed that either the genetic or the shared environmental factors influencing childhood conduct disorder differed for males and females (i.e., a qualitative sex difference), but by adulthood, these sex-specific influences on antisocial behavior were no longer apparent. Further, genetic and environmental influences accounted for proportionally the same amount of variance in antisocial behavior for males and females in childhood and adulthood (i.e., there were no quantitative sex differences). Additionally, the stability of antisocial behavior from childhood to adulthood was slightly greater for males than females. Though familial factors accounted for more of the stability of antisocial behavior for males than females, genetic factors accounted for the majority of the covariation between childhood conduct disorder and adult antisocial behavior for both sexes. The genetic influences on adult antisocial behavior overlapped completely with the genetic influences on childhood conduct disorder for both males and females. Implications for future twin and molecular genetic studies are discussed.

  17. Genetic and environmental influences on individual differences in emotion regulation and its relation to working memory in toddlerhood.

    Science.gov (United States)

    Wang, Manjie; Saudino, Kimberly J

    2013-12-01

    This is the first study to explore genetic and environmental contributions to individual differences in emotion regulation in toddlers, and the first to examine the genetic and environmental etiology underlying the association between emotion regulation and working memory. In a sample of 304 same-sex twin pairs (140 MZ, 164 DZ) at age 3, emotion regulation was assessed using the Behavior Rating Scale of the Bayley Scales of Infant Development (BRS; Bayley, 1993), and working memory was measured by the visually cued recall (VCR) task (Zelazo, Jacques, Burack, & Frye, 2002) and several memory tasks from the Mental Scale of the BSID. Based on model-fitting analyses, both emotion regulation and working memory were significantly influenced by genetic and nonshared environmental factors. Shared environmental effects were significant for working memory, but not for emotion regulation. Only genetic factors significantly contributed to the covariation between emotion regulation and working memory.

  18. Genetic and environmental contributions to anxiety among Chinese children and adolescents--a multi-informant twin study.

    Science.gov (United States)

    Chen, Jie; Yu, Jing; Li, Xinying; Zhang, Jianxin

    2015-05-01

    Child and adolescent anxiety has become a major public health concern in China, but little was known about the etiology of anxiety in Chinese children and adolescents. The present study aimed to investigate genetic and environmental influences on trait anxiety among Chinese children and adolescents. Rater, sex, and age differences on these estimates were also examined. Self-reported and parent-reported child's trait anxiety was collected from 1,104 pairs of same-sex twins aged 9-18 years. Genetic models were fitted to data from each informant to determine the genetic (A), shared (C), and non-shared environmental (E) influences on trait anxiety. The parameter estimates and 95% confidence intervals (CI) of A, C, E on self-reported trait anxiety were 50% [30%, 60%], 5% [0%, 24%], 45% [40%, 49%]. For parent-reported data, the corresponding parameter estimates were 63% [47%, 78%], 13% [1%, 28%], and 24% [22%, 27%], respectively. The heritability of anxiety was higher in girls for self-reported data, but higher in boys for parent-reported data. There was no significant age difference in genetic and environmental contributions for self-reported data, but a significant increase of heritability with age for parent-reported data. The trait anxiety in Chinese children and adolescents was highly heritable. Non-shared environmental factors also played an important role. The estimates of genetic and environmental effects differed by rater, sex and age. Our findings largely suggest the cross-cultural generalizability of the etiological model of child and adolescent anxiety. © 2014 Association for Child and Adolescent Mental Health.

  19. Genetic variation in GABRA2 moderates peer influence on externalizing behavior in adolescents.

    Science.gov (United States)

    Villafuerte, Sandra; Trucco, Elisa M; Heitzeg, Mary M; Burmeister, Margit; Zucker, Robert A

    2014-01-01

    Genetic predisposition and environmental influences are both important factors in the development of problematic behavior leading to substance use in adolescence. Involvement with delinquent peers also strongly predicts adolescent externalizing behavior. Several lines of evidence support a role of GABRA2 on externalizing behavior related to disinhibition. However, whether this genetic association is influenced by the environment such as peer behavior remains unknown. We examined the moderating role of GABRA2 genetic variation on the socialization model of delinquent peer affiliation (at ages 12-14 years) on externalizing behavior (at ages 15-17 years) in the Michigan Longitudinal Study (MLS) adolescent sample. The sample consisted of 244 adolescents (75 females and 152 with at least one parent with a DSM-IV lifetime alcohol dependence/abuse diagnosis). Peer delinquent activity reported by the participant and teacher-reported adolescent externalizing behavior (Teacher Report Form (TRF) were assessed. No main effect of the GABRA2 SNP rs279826, which tags a large haplotype, on externalizing behavior was observed. However, there was a statistically reliable GABRA2 × peer delinquency interaction. The effect of peer delinquent involvement on externalizing scores and the rule breaking subscale is significantly stronger for those with the GG genotype compared to A-carriers, whereas there was no effect of genotype on externalizing in the absence of peer delinquent involvement. No interaction was observed for the aggression subscale. Our results suggest that the genetic effect of GABRA2 on externalizing behavior, more specifically on rule breaking is, at least in part, due to its effect on susceptibility to environmental exposure (i.e., peer delinquency).

  20. Statin-associated myopathy: from genetic predisposition to clinical management.

    Science.gov (United States)

    Vrablik, M; Zlatohlavek, L; Stulc, T; Adamkova, V; Prusikova, M; Schwarzova, L; Hubacek, J A; Ceska, R

    2014-01-01

    Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results.

  1. Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences.

    Science.gov (United States)

    Pluess, Michael

    2017-02-01

    A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. © 2015 Wiley Periodicals, Inc.

  2. The Genetic and Environmental Contributions to Internet Use and Associations With Psychopathology: A Twin Study.

    Science.gov (United States)

    Long, Elizabeth C; Verhulst, Brad; Neale, Michael C; Lind, Penelope A; Hickie, Ian B; Martin, Nicholas G; Gillespie, Nathan A

    2016-02-01

    Excessive internet use has been linked to psychopathology. Therefore, understanding the genetic and environmental risks underpinning internet use and their relation to psychopathology is important. This study aims to explore the genetic and environmental etiology of internet use measures and their associations with internalizing disorders and substance use disorders. The sample included 2,059 monozygotic (MZ) and dizygotic (DZ) young adult twins from the Brisbane Longitudinal Twin Study (BLTS). Younger participants reported more frequent internet use, while women were more likely to use the internet for interpersonal communication. Familial aggregation in 'frequency of internet use' was entirely explained by additive genetic factors accounting for 41% of the variance. Familial aggregation in 'frequency of use after 11 pm', 'using the internet to contact peers', and 'using the internet primarily to access social networking sites' was attributable to varying combinations of additive genetic and shared environmental factors. In terms of psychopathology, there were no significant associations between internet use measures and major depression (MD), but there were positive significant associations between 'frequency of internet use' and 'frequency of use after 11 pm' with social phobia (SP). 'Using the internet to contact peers' was positively associated with alcohol abuse, whereas 'using the internet to contact peers' and 'using the internet primarily to access social networking sites' were negatively associated with cannabis use disorders and nicotine symptoms. Individual differences in internet use can be attributable to varying degrees of genetic and environmental risks. Despite some significant associations of small effect, variation in internet use appears mostly unrelated to psychopathology.

  3. Moderation of genetic and environmental influences on diurnal preference by age in adult twins.

    Science.gov (United States)

    Barclay, Nicola L; Watson, Nathaniel F; Buchwald, Dedra; Goldberg, Jack

    2014-03-01

    Diurnal preference changes across the lifespan. However, the mechanisms underlying this age-related shift are poorly understood. The aim of this twin study was to determine the extent to which genetic and environmental influences on diurnal preference are moderated by age. Seven hundred and sixty-eight monozygotic and 674 dizygotic adult twin pairs participating in the University of Washington Twin Registry completed the reduced Morningness-Eveningness Questionnaire as a measure of diurnal preference. Participants ranged in age from 19 to 93 years (mean = 36.23, SD = 15.54) and were categorized on the basis of age into three groups: younger adulthood (19-35 years, n = 1715 individuals), middle adulthood (36-64 years, n = 1003 individuals) and older adulthood (65+ years, n = 168 individuals). Increasing age was associated with an increasing tendency towards morningness (r = 0.42, p influences for the total sample as well as for each age group separately. Additive genetic influences accounted for 52%[46-57%], and non-shared environmental influences 48%[43-54%], of the total variance in diurnal preference. In comparing univariate genetic models between age groups, the best-fitting model was one in which the parameter estimates for younger adults and older adults were equated, in comparison with middle adulthood. For younger and older adulthood, additive genetic influences accounted for 44%[31-49%] and non-shared environmental influences 56%[49-64%] of variance in diurnal preference, whereas for middle adulthood these estimates were 34%[21-45%] and 66%[55-79%], respectively. Therefore, genetic influences on diurnal preference are attenuated in middle adulthood. Attenuation is likely driven by the increased importance of work and family responsibilities during this life stage, in comparison with younger and older adulthood when these factors may be less influential in determining sleep-wake timing. These findings have implications for studies

  4. Genetic and environmental influences on the familial transmission of externalizing disorders in adoptive and twin offspring.

    Science.gov (United States)

    Hicks, Brian M; Foster, Katherine T; Iacono, William G; McGue, Matt

    2013-10-01

    Twin-family studies have shown that parent-child resemblance on substance use disorders and antisocial behavior can be accounted for by the transmission of a general liability to a spectrum of externalizing disorders. Most studies, however, include only biological parents and offspring, which confound genetic and environmental transmission effects. To examine the familial transmission of externalizing disorders among both adoptive (genetically unrelated) and biological relatives to better distinguish genetic and environmental mechanisms of transmission. Family study design wherein each family included the mother, father, and 2 offspring, including monozygotic twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural equation modeling was used to estimate familial transmission effects and their genetic and environmental influences. Participants were recruited from the community and assessed at a university laboratory. A total of 1590 families with biological offspring and 409 families with adoptive offspring. Offspring participants were young adults (mean age, 26.2 years). Symptom counts of conduct disorder, adult antisocial behavior, and alcohol, nicotine, and drug dependence. RESULTS There was a medium effect for the transmission of the general externalizing liability for biological parents (r = 0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive siblings exhibited significant similarity on the general externalizing liability (r = 0.21). Biometric analyses revealed that the general externalizing liability was highly heritable (a2 = 0.61) but also exhibited significant shared environmental influences (c2 = 0.20). Parent-child resemblance for substance use disorders and antisocial behavior is primarily due to the genetic transmission of a general liability to a spectrum of externalizing disorders. Including adoptive siblings revealed a greater role of shared environmental influences on the general externalizing liability

  5. Guidance on the environmental risk assessment of genetically modified plants

    DEFF Research Database (Denmark)

    Bartsch, Detlef; Chueca, Cristina; De-Schrijver, Adinda

    risk evaluation. The scientific Panel on Genetically Modified Organisms (of the European Food Safety Authority (EFSA GMO Panel) considers seven specific areas of concern to be addressed by applicants and risk assessors during the ERA (1) persistence and invasiveness of the GM plant , or its compatible......This document provides guidance for the environmental risk assessment (ERA) of genetically modified (GM) plants submitted within the framework of Regulation (EC) No. 1829/2003 on GM food and feed or under Directive 2001/18/EC on the deliberate release into the environment of genetically modified...... organisms (GMOs). This document provides guidance for assessing potential effects of GM plants on the environment and the rationales for the data requirements for a comprehensive ERA of GM plants. The ERA should be carried out on a case-by-case basis, following a step-by-step assessment approach...

  6. Genetic and environmental factors in alexithymia: A population-based study of 8.785 Danish twin pairs

    DEFF Research Database (Denmark)

    Jørgensen, Michael Martini; Zachariae, Robert; Skytthe, Axel

    2007-01-01

    by shared (12-20%) and nonshared environmental effects (50-56%). CONCLUSION: The results from this large population-based sample suggest that genetic factors have a noticeable and similar impact on all facets of alexithymia. While the results suggested a moderate influence of shared environmental factors......BACKGROUND: The role of genetic and environmental factors for developing alexithymia is still unclear, and the aim of this study was to examine these factors in a large population-based sample of twins. METHODS: The Toronto Alexithymia Scale-20 (TAS-20) was included in a mail survey of 46...... modeling of the noncategorical data, an ACE model including additive genetic, shared environmental and nonshared environmental effects, provided the best fit for all three facets of alexithymia as well as total alexithymia scores, with heritabilities of 30-33% and the remaining variance being explained...

  7. On the Genetic and Environmental Correlations between Trait Emotional Intelligence and Vocational Interest Factors.

    Science.gov (United States)

    Schermer, Julie Aitken; Petrides, Konstantinos V; Vernon, Philip A

    2015-04-01

    The phenotypic (observed), genetic, and environmental correlations were examined in a sample of adult twins between the four factors and global score of the trait emotional intelligence questionnaire (TEIQue) and the seven vocational interest factors of the Jackson Career Explorer (JCE). Multiple significant correlations were found involving the work style vocational interest factor (consisting of job security, stamina, accountability, planfulness, and interpersonal confidence) and the social vocational interest factor (which included interests in the social sciences, personal services, teaching, social services, and elementary education), both of which correlated significantly with all of the TEIQue variables (well-being, self-control, emotionality, sociability, and global trait EI). Following bivariate genetic analyses, most of the significant phenotypic correlations were found to also have significant genetic correlations as well as significant non-shared (unique) environmental correlations.

  8. Estimates of genetic and environmental factors on growth and mortality in Karakul lambs

    Directory of Open Access Journals (Sweden)

    Sayed Akbar Shiri

    2016-04-01

    Full Text Available Introduction Lamb production is the largest part of income in sheep industry. Therefore, the mortality rate of lambs is a key factor in profit of the sheep breeding. Mortality rate of lambs (or Lamb mortality rate in different breeds of sheep under different climatic conditions is varying from 15% to 50% and an average of 9% to 20% has been reported. Survival rate is a combination trait that is influenced by various factors such as management, weather condition, and behavior of dam and lamb, as well as genetic effects. Quantification of non-genetic effects on mortality rate can be useful in controlling lamb survival rate and increasing profitability of sheep breeding. Therefore, identification of genetic and environmental factors affecting the productive capacity of indigenous breeds in different area is the main priority that should be considered in breeding programmes. Therefore, the objective of this study was to estimate genetic and environmental factors of growth traits and mortality in Karakul lambs. To estimate the genetic and environmental parameters of Karakul lambs before weaning growth and mortality records of 4929 lambs from 207 rams and 1856 ewes at Sarakhs Karakul sheep breeding station, from 1994 to 2009 were used. Materials and Methods The data were used in this study included a total of 4929 record of lamb birth weight, 1 and 3 months of age, average daily gain from birth to weaning (growth traits before weaning and mortality rate of lambs from birth to 1, 2, 4, 8 and 14 weeks (mortality rate of lambs before weaning. Data were collected during the years 1994 to 2010 in karakul breeding station in Sarakhs. The data were edited and pedigree file and data file were prepared. Uni-variate animal model was used to estimate the genetic parameters as following: where is the vector of record, b is the vector of fixed effects (year, sex, type of birth, age of dam, a is the vector of direct additive genetic effects, m the vector of

  9. Genetic and environmental influences on conduct and antisocial personality problems in childhood, adolescence, and adulthood

    NARCIS (Netherlands)

    Wesseldijk, Laura W; Bartels, Meike; Vink, Jacqueline M; van Beijsterveldt, Catharina E M; Ligthart, Lannie; Boomsma, Dorret I; Middeldorp, Christel M

    2017-01-01

    Conduct problems in children and adolescents can predict antisocial personality disorder and related problems, such as crime and conviction. We sought an explanation for such predictions by performing a genetic longitudinal analysis. We estimated the effects of genetic, shared environmental, and

  10. Differential Effects of Environmental and Genetic Factors on T and B Cell Immune Traits

    NARCIS (Netherlands)

    Aguirre-Gamboa, Raul; Joosten, Irma; Urbano, Paulo C. M.; van der Molen, Renate G.; van Rijssen, Esther; van Cranenbroek, Bram; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Zorro, Maria; Withoff, Sebo; van Herwaarden, Antonius E.; Sweep, Fred C. G. J.; Netea, Romana T.; Swertz, Morris A.; Franke, Lude; Xavier, Ramnik J.; Joosten, Leo A. B.; Netea, Mihai G.; Wijmenga, Cisca; Kumar, Vinod; Li, Yang; Koenen, Hans J. P. M.

    2016-01-01

    Effective immunity requires a complex network of cellular and humoral components that interact with each other and are influenced by different environmental and host factors. We used a systems biology approach to comprehensively assess the impact of environmental and genetic factors on immune cell

  11. The Association between Infants' Attention Control and Social Inhibition Is Moderated by Genetic and Environmental Risk for Anxiety

    Science.gov (United States)

    Brooker, Rebecca J.; Neiderhiser, Jenae M.; Kiel, Elizabeth J.; Leve, Leslie D.; Shaw, Daniel S.; Reiss, David

    2011-01-01

    Infant social inhibition is associated with increased risk for anxiety later in life. Although both genetic and environmental factors are associated with anxiety, little empirical work has addressed how developing regulatory abilities work with genetic and environmental risk to exacerbate or mitigate problem behaviors. The current study was aimed…

  12. Continuity of Genetic and Environmental Influences on Cognition across the Life Span: A Meta-Analysis of Longitudinal Twin and Adoption Studies

    Science.gov (United States)

    Tucker-Drob, Elliot M.; Briley, Daniel A.

    2014-01-01

    The longitudinal rank-order stability of cognitive ability increases dramatically over the lifespan. Multiple theoretical perspectives have proposed that genetic and/or environmental mechanisms underlie the longitudinal stability of cognition, and developmental trends therein. However, the patterns of stability of genetic and environmental influences on cognition over the lifespan largely remain poorly understood. We searched for longitudinal studies of cognition that reported raw genetically-informative longitudinal correlations or parameter estimates from longitudinal behavior genetic models. We identified 150 combinations of time points and measures from 15 independent longitudinal samples. In total, longitudinal data came from 4,538 monozygotic twin pairs raised together, 7,777 dizygotic twin pairs raised together, 34 monozygotic twin pairs raised apart, 78 dizygotic twin pairs raised apart, 141 adoptive sibling pairs, and 143 non-adoptive sibling pairs, ranging in age from infancy through late adulthood. At all ages, cross-time genetic correlations and shared environmental correlations were substantially larger than cross-time nonshared environmental correlations. Cross-time correlations for genetic and shared environmental components were low during early childhood, increased sharply over child development, and remained relatively high from adolescence through late adulthood. Cross-time correlations for nonshared environmental components were low across childhood and increased gradually to moderate magnitudes in adulthood. Increasing phenotypic stability over child development was almost entirely mediated by genetic factors. Time-based decay of genetic and shared environmental stability was more pronounced earlier in child development. Results are interpreted in reference to theories of gene-environment interaction and correlation. PMID:24611582

  13. Assessing environmental impacts of genetically modified plants on non-target organisms

    NARCIS (Netherlands)

    Arpaia, Salvatore; Birch, A.N.E.; Kiss, Jozsef; Loon, van Joop J.A.; Messéan, Antoine; Nuti, Marco; Perry, Joe N.; Sweet, Jeremy B.; Tebbe, Christoph C.

    2017-01-01

    In legal frameworks worldwide, genetically modified plants (GMPs) are subjected to pre-market environmental risk assessment (ERA) with the aim of identifying potential effects on the environment. In the European Union, the EFSA Guidance Document introduces the rationale that GMPs, as well as their

  14. Beliefs about the Etiology of Homosexuality and about the Ramifications of Discovering Its Possible Genetic Origin

    Science.gov (United States)

    Sheldon, Jane P.; Pfeffer, Carla A.; Jayaratne, Toby Epstein; Feldbaum, Merle; Petty, Elizabeth M.

    2013-01-01

    Homosexuality is viewed by many as a social problem. As such, there has been keen interest in elucidating the origins of homosexuality among many scholars, from anthropologists to zoologists, psychologists to theologians. Research has shown that those who believe sexual orientation is inborn are more likely to have tolerant attitudes toward gay men and lesbians, whereas those who believe it is a choice have less tolerant attitudes. The current qualitative study used in-depth, open-ended telephone interviews with 42 White and 44 Black Americans to gain insight into the public's beliefs about the possible genetic origins of homosexuality. Along with etiological beliefs (and the sources of information used to develop those beliefs), we asked respondents to describe the benefits and dangers of scientists discovering the possible genetic basis for homosexuality. We found that although limited understanding and biased perspectives likely led to simplistic reasoning concerning the origins and genetic basis of homosexuality, many individuals appreciated complex and interactive etiological perspectives. These interactive perspectives often included recognition of some type of inherent aspect, such as a genetic factor(s), that served as an underlying predisposition that would be manifested after being influenced by other factors such as choice or environmental exposures. We also found that beliefs in a genetic basis for homosexuality could be used to support very diverse opinions, including those in accordance with negative eugenic agendas. PMID:17594974

  15. Parental rearing and psychopathology in mothers of adolescents with and without borderline personality symptoms

    NARCIS (Netherlands)

    Schuppert, H.M.; Albers, C.J.; Minderaa, R.B.; Emmelkamp, P.M.G.; Nauta, M.H.

    2012-01-01

    Background: A combination of multiple factors, including a strong genetic predisposition and environmental factors, are considered to contribute to the developmental pathways to borderline personality disorder (BPD). However, these factors have mostly been investigated retrospectively, and hardly in

  16. Changes in genetic and environmental influences on disordered eating between early and late adolescence: a longitudinal twin study.

    Science.gov (United States)

    Fairweather-Schmidt, A K; Wade, T D

    2015-11-01

    We investigated the genetic and environmental contributions to disordered eating (DE) between early and late adolescence in order to determine whether different sources of heritability and environmental risk contributed to these peak times of emergence of eating disorders. Adolescent female twins from the Australian Twin Registry were interviewed over the telephone with the Eating Disorder Examination (EDE). Data were collected at 12-15 and 16-19 years (wave 1: N = 699, 351 pairs; wave 3: N = 499, 247 pairs). Assessments also involved self-report measures related to negative life events and weight-related peer teasing. Unstandardized estimates from the bivariate Cholesky decomposition model showed both genetic influences and non-shared environmental influences increased over adolescence, but shared environmental influences decreased. While non-shared environmental sources active at ages 12-15 years continued to contribute at 16-19 years, new sources of both additive genetic and non-shared environmental risk were introduced at ages 16-19 years. Weight-related peer teasing in early-mid adolescence predicted increases of DE in later adolescence, while negative life events did not. Two-thirds of the heritable influence contributing to DE in late adolescence was unique to this age group. During late adolescence independent sources of genetic risk, as well as environmental influences are likely to be related in part to peer teasing, appear key antecedents in growth of DE.

  17. Enabling complex genetic circuits to respond to extrinsic environmental signals.

    Science.gov (United States)

    Hoynes-O'Connor, Allison; Shopera, Tatenda; Hinman, Kristina; Creamer, John Philip; Moon, Tae Seok

    2017-07-01

    Genetic circuits have the potential to improve a broad range of metabolic engineering processes and address a variety of medical and environmental challenges. However, in order to engineer genetic circuits that can meet the needs of these real-world applications, genetic sensors that respond to relevant extrinsic and intrinsic signals must be implemented in complex genetic circuits. In this work, we construct the first AND and NAND gates that respond to temperature and pH, two signals that have relevance in a variety of real-world applications. A previously identified pH-responsive promoter and a temperature-responsive promoter were extracted from the E. coli genome, characterized, and modified to suit the needs of the genetic circuits. These promoters were combined with components of the type III secretion system in Salmonella typhimurium and used to construct a set of AND gates with up to 23-fold change. Next, an antisense RNA was integrated into the circuit architecture to invert the logic of the AND gate and generate a set of NAND gates with up to 1168-fold change. These circuits provide the first demonstration of complex pH- and temperature-responsive genetic circuits, and lay the groundwork for the use of similar circuits in real-world applications. Biotechnol. Bioeng. 2017;114: 1626-1631. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Dandelion (Taraxacum Officinale Wigg. S.L. Is A Convenient Object For Genetic Monitoring Of Environmental Pollution

    Directory of Open Access Journals (Sweden)

    Nina V Reutova

    2006-09-01

    Full Text Available It is proposed to use dandelion (Taraxacum officinale Wigg. s.l. for testing of mutagenic effects of environmental pollutants. This widespread species is convenient for genetic monitoring. It is sensitive to various types of pollutants (heavy metals, products of combustion and processing of oil. T. officinale appeared to be a convenient, simple in using and inexpensive object for genetic monitoring of environmental pollution. anaphase-telophase method is recomended for this purpose.

  19. Moderation of Harsh Parenting on Genetic and Environmental Contributions to Child and Adolescent Deviant Peer Affiliation: A Longitudinal Twin Study.

    Science.gov (United States)

    Li, Mengjiao; Chen, Jie; Li, Xinying; Deater-Deckard, Kirby

    2015-07-01

    Affiliation with deviant peers is associated with biologically influenced personal attributes, and is itself a major contributor to growth in antisocial behavior over childhood and adolescence. Several studies have shown that variance in child and adolescent deviant peer affiliation includes genetic and non-genetic influences, but none have examined longitudinal genetic and environmental stability or change within the context of harsh parenting. To address this gap, we tested the moderating role of harsh parenting on genetic and environmental stability or change of deviant peer affiliation in a longitudinal (spanning one and a half years) study of Chinese child and adolescent twin pairs (N = 993, 52.0% female). Using multiple informants (child- and parent-reports) and measurement methods to minimize rater bias, we found that individual differences in deviant peer affiliation at each assessment were similarly explained by moderate genetic and nonshared environmental variance. The longitudinal stability and change of deviant peer affiliation were explained by genetic and nonshared environmental factors. The results also revealed that the genetic variance for deviant peer affiliation is higher in the families with harsher parenting. This amplified genetic risk underscores the role of harsh parenting in the selection and socialization process of deviant peer relationships.

  20. Assessment of the environmental and genetic factors influencing prevalence of metabolic syndrome in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Ibrahim M. Gosadi

    2016-01-01

    Full Text Available Metabolic syndrome (MS is a combination of factors that increases the risk of cardiovascular atherosclerotic diseases including diabetes, obesity, dyslipidemia, and high blood pressure. Cardiovascular diseases are one of the leading causes of death in the adult Saudi population where the increase in cardiovascular-related mortality is augmented by the rise in the prevalence of MS. Metabolic syndrome is a multi-factorial disorder influenced by interactions between genetic and environmental components. This review aims to provide a comprehensive assessment of studied environmental and genetic factors explaining the prevalence of MS in the Kingdom of Saudi Arabia. Additionally, this review aims to illustrate factors related to the population genetics of Saudi Arabia, which might explain a proportion of the prevalence of MS.

  1. Assessment of the environmental and genetic factors influencing prevalence of metabolic syndrome in Saudi Arabia

    Science.gov (United States)

    Gosadi, Ibrahim M.

    2016-01-01

    Metabolic syndrome (MS) is a combination of factors that increases the risk of cardiovascular atherosclerotic diseases including diabetes, obesity, dyslipidemia, and high blood pressure. Cardiovascular diseases are one of the leading causes of death in the adult Saudi population where the increase in cardiovascular-related mortality is augmented by the rise in the prevalence of MS. Metabolic syndrome is a multi-factorial disorder influenced by interactions between genetic and environmental components. This review aims to provide a comprehensive assessment of studied environmental and genetic factors explaining the prevalence of MS in the Kingdom of Saudi Arabia. Additionally, this review aims to illustrate factors related to the population genetics of Saudi Arabia, which might explain a proportion of the prevalence of MS. PMID:26739969

  2. Syndromic Gastric Polyps : At the Crossroads of Genetic and Environmental Cancer Predisposition

    NARCIS (Netherlands)

    Brosens, Lodewijk A A; Giardiello, Francis M; Offerhaus, G Johan; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare

  3. The McGill Interactive Pediatric OncoGenetic Guidelines: An approach to identifying pediatric oncology patients most likely to benefit from a genetic evaluation.

    Science.gov (United States)

    Goudie, Catherine; Coltin, Hallie; Witkowski, Leora; Mourad, Stephanie; Malkin, David; Foulkes, William D

    2017-08-01

    Identifying cancer predisposition syndromes in children with tumors is crucial, yet few clinical guidelines exist to identify children at high risk of having germline mutations. The McGill Interactive Pediatric OncoGenetic Guidelines project aims to create a validated pediatric guideline in the form of a smartphone/tablet application using algorithms to process clinical data and help determine whether to refer a child for genetic assessment. This paper discusses the initial stages of the project, focusing on its overall structure, the methodology underpinning the algorithms, and the upcoming algorithm validation process. © 2017 Wiley Periodicals, Inc.

  4. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    DEFF Research Database (Denmark)

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo

    2016-01-01

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic...

  5. Genetic variance in micro-environmental sensitivity for milk and milk quality in Walloon Holstein cattle.

    Science.gov (United States)

    Vandenplas, J; Bastin, C; Gengler, N; Mulder, H A

    2013-09-01

    Animals that are robust to environmental changes are desirable in the current dairy industry. Genetic differences in micro-environmental sensitivity can be studied through heterogeneity of residual variance between animals. However, residual variance between animals is usually assumed to be homogeneous in traditional genetic evaluations. The aim of this study was to investigate genetic heterogeneity of residual variance by estimating variance components in residual variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027 test-day records from 26,887 cows in 747 herds were available. All cows had at least 3 records and a known sire. These sires had at least 10 cows with records and each herd × test-day had at least 5 cows. The 5 traits were analyzed separately based on fixed lactation curve and random regression test-day models for the mean. Estimation of variance components was performed by running iteratively expectation maximization-REML algorithm by the implementation of double hierarchical generalized linear models. Based on fixed lactation curve test-day mean models, heritability for residual variances ranged between 1.01×10(-3) and 4.17×10(-3) for all traits. The genetic standard deviation in residual variance (i.e., approximately the genetic coefficient of variation of residual variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro-environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5 studied traits. The standard deviations due to herd × test-day and permanent environment in residual variance ranged between 0.36 and 0.45 for herd × test-day effect and between 0.55 and 0.97 for permanent environmental effect. Therefore, nongenetic effects also

  6. Detection vs. selection: integration of genetic, epigenetic and environmental cues in fluctuating environments.

    Science.gov (United States)

    McNamara, John M; Dall, Sasha R X; Hammerstein, Peter; Leimar, Olof

    2016-10-01

    There are many inputs during development that influence an organism's fit to current or upcoming environments. These include genetic effects, transgenerational epigenetic influences, environmental cues and developmental noise, which are rarely investigated in the same formal framework. We study an analytically tractable evolutionary model, in which cues are integrated to determine mature phenotypes in fluctuating environments. Environmental cues received during development and by the mother as an adult act as detection-based (individually observed) cues. The mother's phenotype and a quantitative genetic effect act as selection-based cues (they correlate with environmental states after selection). We specify when such cues are complementary and tend to be used together, and when using the most informative cue will predominate. Thus, we extend recent analyses of the evolutionary implications of subsets of these effects by providing a general diagnosis of the conditions under which detection and selection-based influences on development are likely to evolve and coexist. © 2016 John Wiley & Sons Ltd/CNRS.

  7. Developing genetic privacy legislation: the South Carolina experience.

    Science.gov (United States)

    Edwards, J G; Young, S R; Brooks, K A; Aiken, J H; Patterson, E D; Pritchett, S T

    1998-01-01

    The availability of presymptomatic and predisposition genetic testing has spawned the need for legislation prohibiting health insurance discrimination on the basis of genetic information. The federal effort, the Health Insurance Portability and Accountability Act (HIPAA) of 1996, falls short by protecting only those who access insurance through group plans. A committee of University of South Carolina professionals convened in 1996 to develop legislation in support of genetic privacy for the state of South Carolina. The legislation prevents health insurance companies from denying coverage or setting insurance rates on the basis of genetic information. It also protects the privacy of genetic information and prohibits performance of genetic tests without specific informed consent. In preparing the bill, genetic privacy laws from other states were reviewed, and a modified version of the Virginia law adopted. The South Carolina Committee for the Protection of Genetic Privacy version went a step further by including enforcement language and excluding Virginia's sunset clause. The definition of genetic information encompassed genetic test results, and importantly, includes family history of genetic disease. Our experience in navigating through the state legislature and working through opposition from the health insurance lobby is detailed herein.

  8. A study of changes in genetic and environmental influences on weight and shape concern across adolescence.

    Science.gov (United States)

    Wade, Tracey D; Hansell, Narelle K; Crosby, Ross D; Bryant-Waugh, Rachel; Treasure, Janet; Nixon, Reginald; Byrne, Susan; Martin, Nicholas G

    2013-02-01

    The goal of the current study was to examine whether genetic and environmental influences on an important risk factor for disordered eating, weight and shape concern, remained stable over adolescence. This stability was assessed in 2 ways: whether new sources of latent variance were introduced over development and whether the magnitude of variance contributing to the risk factor changed. We examined an 8-item WSC subscale derived from the Eating Disorder Examination (EDE) using telephone interviews with female adolescents. From 3 waves of data collected from female-female same-sex twin pairs from the Australian Twin Registry, a subset of the data (which included 351 pairs at Wave 1) was used to examine 3 age cohorts: 12 to 13, 13 to 15, and 14 to 16 years. The best-fitting model contained genetic and environmental influences, both shared and nonshared. Biometric model fitting indicated that nonshared environmental influences were largely specific to each age cohort, and results suggested that latent shared environmental and genetic influences that were influential at 12 to 13 years continued to contribute to subsequent age cohorts, with independent sources of both emerging at ages 13 to 15. The magnitude of all 3 latent influences could be constrained to be the same across adolescence. Ages 13 to 15 were indicated as a time of risk for the development of high levels of WSC, given that most specific environmental risk factors were significant at this time (e.g., peer teasing about weight, adverse life events), and indications of the emergence of new sources of latent genetic and environmental variance over this period. 2013 APA, all rights reserved

  9. Environmental Noise, Genetic Diversity and the Evolution of Evolvability and Robustness in Model Gene Networks

    Science.gov (United States)

    Steiner, Christopher F.

    2012-01-01

    The ability of organisms to adapt and persist in the face of environmental change is accepted as a fundamental feature of natural systems. More contentious is whether the capacity of organisms to adapt (or “evolvability”) can itself evolve and the mechanisms underlying such responses. Using model gene networks, I provide evidence that evolvability emerges more readily when populations experience positively autocorrelated environmental noise (red noise) compared to populations in stable or randomly varying (white noise) environments. Evolvability was correlated with increasing genetic robustness to effects on network viability and decreasing robustness to effects on phenotypic expression; populations whose networks displayed greater viability robustness and lower phenotypic robustness produced more additive genetic variation and adapted more rapidly in novel environments. Patterns of selection for robustness varied antagonistically with epistatic effects of mutations on viability and phenotypic expression, suggesting that trade-offs between these properties may constrain their evolutionary responses. Evolution of evolvability and robustness was stronger in sexual populations compared to asexual populations indicating that enhanced genetic variation under fluctuating selection combined with recombination load is a primary driver of the emergence of evolvability. These results provide insight into the mechanisms potentially underlying rapid adaptation as well as the environmental conditions that drive the evolution of genetic interactions. PMID:23284934

  10. Genetic control of environmental variation of two quantitative traits of Drosophila melanogaster revealed by whole-genome sequencing

    DEFF Research Database (Denmark)

    Sørensen, Peter; de los Campos, Gustavo; Morgante, Fabio

    2015-01-01

    and others more volatile performance. Understanding the mechanisms responsible for environmental variability not only informs medical questions but is relevant in evolution and in agricultural science. In this work fully sequenced inbred lines of Drosophila melanogaster were analyzed to study the nature...... of genetic control of environmental variance for two quantitative traits: starvation resistance (SR) and startle response (SL). The evidence for genetic control of environmental variance is compelling for both traits. Sequence information is incorporated in random regression models to study the underlying...... genetic signals, which are shown to be different in the two traits. Genomic variance in sexual dimorphism was found for SR but not for SL. Indeed, the proportion of variance captured by sequence information and the contribution to this variance from four chromosome segments differ between sexes in SR...

  11. Genetic studies of type 2 diabetes in South Asians: a systematic overview.

    Science.gov (United States)

    Chowdhury, Ritam; Narayan, Kabayam M Venkat; Zabetian, Azadeh; Raj, Suraja; Tabassum, Rubina

    2014-01-01

    Diabetes Mellitus, which affects 366 million people worldwide, is a leading cause of mortality, morbidity, and loss of quality of life. South Asians, comprising 24% of the world's population, suffer a large burden of type 2 diabetes. With intriguing risk phenotypes, unique environmental triggers, and potential genetic predisposition, South Asians offer a valuable resource for investigating the pathophysiology of type 2 diabetes. Genomics has proven its potential to underpin some of the etiology of type 2 diabetes by identifying a number of susceptibility genes, but such data are scarce and unclear in South Asians. We present a systematic review of studies on the genetic basis of type 2 diabetes or its complications in South Asians published between 1987-2012, and discuss the findings and limitations of the available data. Of the 91 eligible studies meeting our inclusion criteria, a vast majority included Indian populations, followed by a few in those of Pakistani origin, while other South Asian countries were generally under-represented. Though a large number of studies focused on the replication of findings from genome-wide association studies (GWAS) in European populations, a few studies explored new genes and pathways along with GWAS in South Asians and suggested the potential to unravel population- specific susceptibility genes in this population. We find encouraging improvements in study designs, sample sizes and the numbers of genetic variants investigated over the last five years, which reflect the existing capacity and scope for large-scale genetic studies in South Asians.

  12. Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Scott, D. [Christie Hospital, Manchester (United Kingdom). Paterson Inst. for Cancer Research

    2000-05-01

    Aim: This paper briefly summarizes the research on this topic, undertaken in the Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, England, over the previous 6 years. We have investigated the possible role of radiosensitivity as a marker of cancer predisposition and response to radiotherapy in the general population. Results: We found that 42% (57/135) of breast cancer patients exhibit chromosomal radiosensitivity when lymphocytes are irradiated in the G{sub 2} phase of the cell cycle, compared with 6% (6/105) of healthy controls. These figures are much higher than the estimated frequencies of carriers of the ataxia-telangiectasia gene (heterozygotes) amongst breast cancer patients (<5%) and control (0.5%). We have also obtained evidence of heritability of G{sub 2} sensitivity by studying relatives of breast cancer cases. The pattern of inheritance is relatively simple and attributable to 1 or 2 genes segregating in each family. In a prospective study of 123 breast cancer patients, 9 (7%) had severe acute reactions to radiotherapy and their mean G{sub 2} sensitivity was significantly greater (p=0.001) than that of the remaining patients. In 16 patients with adverse acute reactions we found no mutations of the ataxia-telangiectasia gene (ATM). Using another chromosomal assay (micronucleus induction in G{sub 0} lymphocytes) we found that the mean radiosensitivity of patients with severe late reactions was higher than that of normal reactors. For example, 8 patients with severe fibrosis were more sensitive (p=0.055) than 39 patients with a normal response. However, the discriminatory power of these chromosomal assays is too low for them to be used alone in a clinical setting. Conclusion: Our results provide good evidence that genes other than ATM, that confer chromosomal radiosensitivity, are involved in low penetrance predisposition to breast cancer in a high proportion of cases and contribute to adverse reactions after radiotherapy

  13. Combat exposure severity as a moderator of genetic and environmental liability to post-traumatic stress disorder.

    Science.gov (United States)

    Wolf, E J; Mitchell, K S; Koenen, K C; Miller, M W

    2014-05-01

    Twin studies of veterans and adults suggest that approximately 30-46% of the variance in post-traumatic stress disorder (PTSD) is attributable to genetic factors. The remaining variance is attributable to the non-shared environment, which, by definition, includes combat exposure. This study used a gene by measured environment twin design to determine whether the effects of genetic and environmental factors that contribute to the etiology of PTSD are dependent on the level of combat exposure. The sample was drawn from the Vietnam Era Twin Registry (VETR) and included 620 male-male twin pairs who served in the US Military in South East Asia during the Vietnam War era. Analyses were based on data from a clinical diagnostic interview of lifetime PTSD symptoms and a self-report measure of combat exposure. Biometric modeling revealed that the effects of genetic and non-shared environment factors on PTSD varied as a function of level of combat exposure such that the association between these factors and PTSD was stronger at higher levels of combat exposure. Combat exposure may act as a catalyst that augments the impact of hereditary and environmental contributions to PTSD. Individuals with the greatest exposure to combat trauma were at increased risk for PTSD as a function of both genetic and environmental factors. Additional work is needed to determine the biological and environmental mechanisms driving these associations.

  14. Sports participation during adolescence: a shift from environmental to genetic factors

    NARCIS (Netherlands)

    Stubbe, J.H.; Boomsma, D.I.; de Geus, J.C.N.

    2005-01-01

    Purpose: A twin design was used to assess the relative contribution of genetic and environmental influences on the variation in sports participation of Dutch male and female twins between the ages of 13 and 20 yr. Methods: Survey data from 2628 complete twin pairs were available (443 male and 652

  15. Viva la Familia Study: genetic and environmental contributions to childhood obesity and its comorbidities in the Hispanic population.

    Science.gov (United States)

    Butte, Nancy F; Cai, Guowen; Cole, Shelley A; Comuzzie, Anthony G

    2006-09-01

    Genetic and environmental contributions to childhood obesity are poorly delineated. The Viva la Familia Study was designed to genetically map childhood obesity and its comorbidities in the Hispanic population. The objectives of this report were to describe the study design and to summarize genetic and environmental contributions to the phenotypic variation in obesity and risk factors for metabolic diseases in Hispanic children. The Viva la Familia cohort consisted of 1030 children from 319 families selected based on an overweight proband between the ages of 4 and 19 y. In-depth phenotyping to characterize the overweight children and their siblings included anthropometric and body-composition traits by dual-energy X-ray absorptiometry and assessments of diet by 24-h recalls, physical activity by accelerometry, and risk factors for metabolic diseases by standard biochemical methods. Univariate quantitative genetic analysis was used to partition phenotypic variance into additive genetic and environmental components by using the computer program SOLAR. Sex, age, and environmental covariates explained 1-91% of the phenotypic variance. Heritabilities of anthropometric indexes ranged from 0.24 to 0.75. Heritability coefficients for the body-composition traits ranged from 0.18 to 0.35. Diet and physical activity presented heritabilities of 0.32 to 0.69. Risk factors for metabolic diseases were heritable with coefficients ranging from 0.25 to 0.73. Significant genetic correlations between obesity traits and risk factors for metabolic diseases substantiated pleiotropy between traits. The Viva la Familia Study provides evidence of a strong genetic contribution to the high prevalence of obesity and its comorbidities in Hispanic children.

  16. Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study.

    Directory of Open Access Journals (Sweden)

    Guang-Hui Dong

    Full Text Available BACKGROUND: Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship. METHODOLOGY/PRINCIPAL FINDINGS: 30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM(10, sulfur dioxide (SO(2, nitrogen dioxides (NO(2, ozone (O(3 and carbon monoxide (CO. A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs per interquartile changes for PM(10, SO(2, NO(2, O(3, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM(10 (ORs = 1.36 per 31 µg/m(3; 95% CI, 1.08-1.72, SO(2 (ORs = 1.38 per 21 µg/m(3; 95%CI, 1.12-1.69 only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO(2 (ORs = 1.48 per 21 µg/m(3; 95%CI, 1.21-1.80, NO(2 (ORs = 1.26 per 10 µg/m(3; 95%CI, 1.01-1.56, and current asthma with

  17. Epidemiology and genetics of ventricular fibrillation during acute myocardial infarction

    DEFF Research Database (Denmark)

    Glinge, Charlotte; Sattler, Stefan; Jabbari, Reza

    2016-01-01

    of a family member is a risk factor for SCD and VF during acute myocardial infarction (MI), independent of traditional risk factors including family history of MI, suggesting a genetic component in the susceptibility to VF. To prevent SCD and VF due to MI, we need a better understanding of the genetic...... and molecular mechanisms causing VF in this apparently healthy population. Even though new insights and technologies have become available, the genetic predisposition to VF during MI remains poorly understood. Findings from a variety of different genetic studies have failed to reach reproducibility, although...... several genetic variants, both common and rare variants, have been associated to either VF or SCD. For this review, we searched PubMed for potentially relevant articles, using the following MeSH-terms: "sudden cardiac death", "ventricular fibrillation", "out-of-hospital cardiac arrest", "myocardial...

  18. Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

    DEFF Research Database (Denmark)

    Benyamin, B.; Sørensen, T.I.A.; Schousboe, K.

    2007-01-01

    and environmental factors influencing this cluster in a general population of twin pairs. MATERIALS AND METHODS: A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. RESULTS: All......AIMS/HYPOTHESIS: The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic...... endophenotypes showed moderate to high heritability (0.31-0.69) and small common environmental variance (0.05-0.21). In general, genetic and phenotypic correlations between the endophenotypes were strong only within sets of physiologically similar endophenotypes, but weak to moderate for other pairs...

  19. Genetic and environmental components of female depression as a function of the severity of the disorder.

    Science.gov (United States)

    Rusby, James S M; Tasker, Fiona; Cherkas, Lynn

    2016-10-01

    Both clinical care and genome-wide studies need to account for levels of severity in the etiology of depression. The purpose of the study is to estimate the genetic and environmental components of female depression as a function of the severity of the disorder. A genetic and environmental model analysis of depression incidence was made using the IOP Depression Severity Measure (IDSM). Details of lifetime depression incidence were obtained by questionnaire from twins on the DTR registry. Data from 1449 matched female twin pairs in the age range 19-85 years in four ordinal categories of increasing severity were employed in the analysis. Estimates of additive and dominance genetic components of 27% and 25% were found when all three levels of depression were included, and near zero and 33% when the recurrent/severe level was excluded. Shared environmental effects were not significant in either case, but the estimate for random environmental effects was greater when the severe level was excluded. These results suggest that the incidence of severe depression is associated with homozygotic alleles and the less severe with heterozygotic alleles. This is in accord with the finding that the hereditary component of severe depression is relatively high and that milder forms are more dependent on life-time environmental factors. Such conclusions have clinical implications for the diagnosis and treatment of the disorder by practicing psychiatrists. They also lead to the importance of focusing future genome-wide and linkage studies on those females with severe levels of depression if progress in identifying genetic risk loci is to be made.

  20. Neuroimmunomodulation of the young brain. Nutrition, a gut feeling

    OpenAIRE

    de Theije, C.G.M.

    2014-01-01

    Neurodevelopmental disorders, such as autism spectrum disorder (ASD), are heterogeneous conditions, in which both genetic predisposition and environmental factors play a role. Prenatal environmental factors such as maternal immune activation, deficient nutrition, and drugs use during pregnancy increase the risk of neurodevelopmental disorders in the newborn. Also during postnatal development, environmental factors can have a persistent impact on brain development. It is hypothesized that (all...

  1. Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen costimulation.

    Science.gov (United States)

    Walker, Matthew T; Green, Jeremy E; Ferrie, Ryan P; Queener, Ashley M; Kaplan, Mark H; Cook-Mills, Joan M

    2018-02-15

    Mechanisms for the development of food allergy in neonates are unknown but clearly linked in patient populations to a genetic predisposition to skin barrier defects. Whether skin barrier defects contribute functionally to development of food allergy is unknown. The purpose of the study was to determine whether skin barrier mutations, which are primarily heterozygous in patient populations, contribute to the development of food allergy. Mice heterozygous for the filaggrin (Flg) ft and Tmem79 ma mutations were skin sensitized with environmental and food allergens. After sensitization, mice received oral challenge with food allergen, and then inflammation, inflammatory mediators, and anaphylaxis were measured. We define development of inflammation, inflammatory mediators, and food allergen-induced anaphylaxis in neonatal mice with skin barrier mutations after brief concurrent cutaneous exposure to food and environmental allergens. Moreover, neonates of allergic mothers have increased responses to suboptimal sensitization with food allergens. Importantly, responses to food allergens by these neonatal mice were dependent on genetic defects in skin barrier function and on exposure to environmental allergens. ST2 blockade during skin sensitization inhibited the development of anaphylaxis, antigen-specific IgE, and inflammatory mediators. Neonatal anaphylactic responses and antigen-specific IgE were also inhibited by oral pre-exposure to food allergen, but interestingly, this was blunted by concurrent pre-exposure of the skin to environmental allergen. These studies uncover mechanisms for food allergy sensitization and anaphylaxis in neonatal mice that are consistent with features of human early-life exposures and genetics in patients with clinical food allergy and demonstrate that changes in barrier function drive development of anaphylaxis to food allergen. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Genetic and Environmental Effects on Stuttering: A Twin Study from Finland

    Science.gov (United States)

    Rautakoski, Pirkko; Hannus, Therese; Simberg, Susanna; Sandnabba, N. Kenneth; Santtila, Pekka

    2012-01-01

    The present study explored the prevalence of self-reported stuttering in a Finnish twin population and examined the extent to which the variance in liability to stuttering was attributable to genetic and environmental effects. We analyzed data of 1728 Finnish twins, born between 1961 and 1989. The participants were asked to complete a…

  3. Migratory decisions in birds: Extent of genetic versus environmental control

    Science.gov (United States)

    Ogonowski, M.S.; Conway, C.J.

    2009-01-01

    Migration is one of the most spectacular of animal behaviors and is prevalent across a broad array of taxa. In birds, we know much about the physiological basis of how birds migrate, but less about the relative contribution of genetic versus environmental factors in controlling migratory tendency. To evaluate the extent to which migratory decisions are genetically determined, we examined whether individual western burrowing owls (Athene cunicularia hypugaea) change their migratory tendency from one year to the next at two sites in southern Arizona. We also evaluated the heritability of migratory decisions by using logistic regression to examine the association between the migratory tendency of burrowing owl parents and their offspring. The probability of migrating decreased with age in both sexes and adult males were less migratory than females. Individual owls sometimes changed their migratory tendency from one year to the next, but changes were one-directional: adults that were residents during winter 2004-2005 remained residents the following winter, but 47% of adults that were migrants in winter 2004-2005 became residents the following winter. We found no evidence for an association between the migratory tendency of hatch-year owls and their male or female parents. Migratory tendency of hatch-year owls did not differ between years, study sites or sexes or vary by hatching date. Experimental provision of supplemental food did not affect these relationships. All of our results suggest that heritability of migratory tendency in burrowing owls is low, and that intraspecific variation in migratory tendency is likely due to: (1) environmental factors, or (2) a combination of environmental factors and non-additive genetic variation. The fact that an individual's migratory tendency can change across years implies that widespread anthropogenic changes (i.e., climate change or changes in land use) could potentially cause widespread changes in the migratory tendency of

  4. Sensitivity to Peer Evaluation and Its Genetic and Environmental Determinants: Findings from a Population-Based Twin Study.

    Science.gov (United States)

    Klippel, Annelie; Reininghaus, Ulrich; Viechtbauer, Wolfgang; Decoster, Jeroen; Delespaul, Philippe; Derom, Cathérine; de Hert, Marc; Jacobs, Nele; Menne-Lothmann, Claudia; Rutten, Bart; Thiery, Evert; van Os, Jim; van Winkel, Ruud; Myin-Germeys, Inez; Wichers, Marieke

    2018-02-23

    Adolescents and young adults are highly focused on peer evaluation, but little is known about sources of their differential sensitivity. We examined to what extent sensitivity to peer evaluation is influenced by interacting environmental and genetic factors. A sample of 354 healthy adolescent twin pairs (n = 708) took part in a structured, laboratory task in which they were exposed to peer evaluation. The proportion of the variance in sensitivity to peer evaluation due to genetic and environmental factors was estimated, as was the association with specific a priori environmental risk factors. Differences in sensitivity to peer evaluation between adolescents were explained mainly by non-shared environmental influences. The results on shared environmental influences were not conclusive. No impact of latent genetic factors or gene-environment interactions was found. Adolescents with lower self-rated positions on the social ladder or who reported to have been bullied more severely showed significantly stronger responses to peer evaluation. Not genes, but subjective social status and past experience of being bullied seem to impact sensitivity to peer evaluation. This suggests that altered response to peer evaluation is the outcome of cumulative sensitization to social interactions.

  5. Genetic relationships between detailed reproductive traits and performance traits in Holstein-Friesian dairy cattle.

    Science.gov (United States)

    Carthy, T R; Ryan, D P; Fitzgerald, A M; Evans, R D; Berry, D P

    2016-02-01

    The objective of the study was to estimate the genetic relationships between detailed reproductive traits derived from ultrasound examination of the reproductive tract and a range of performance traits in Holstein-Friesian dairy cows. The performance traits investigated included calving performance, milk production, somatic cell score (i.e., logarithm transformation of somatic cell count), carcass traits, and body-related linear type traits. Detailed reproductive traits included (1) resumed cyclicity at the time of examination, (2) multiple ovulations, (3) early ovulation, (4) heat detection, (5) ovarian cystic structures, (6) embryo loss, and (7) uterine score, measured on a 1 (little or no fluid with normal tone) to 4 (large quantity of fluid with a flaccid tone) scale, based on the tone of the uterine wall and the quantity of fluid present in the uterus. (Co)variance components were estimated using a repeatability animal linear mixed model. Genetic merit for greater milk, fat, and protein yield was associated with a reduced ability to resume cyclicity postpartum (genetic correlations ranged from -0.25 to -0.15). Higher genetic merit for milk yield was also associated with a greater genetic susceptibility to multiple ovulations. Genetic predisposition to elevated somatic cell score was associated with a decreased likelihood of cyclicity postpartum (genetic correlation of -0.32) and a greater risk of both multiple ovulations (genetic correlation of 0.25) and embryo loss (genetic correlation of 0.32). Greater body condition score was genetically associated with an increased likelihood of resumption of cyclicity postpartum (genetic correlation of 0.52). Genetically heavier, fatter carcasses with better conformation were also associated with an increased likelihood of resumed cyclicity by the time of examination (genetic correlations ranged from 0.24 to 0.41). Genetically heavier carcasses were associated with an inferior uterine score as well as a greater

  6. dnAGEnetics: genomic copy number variants and parental age as risk factors for psychiatric disorders

    NARCIS (Netherlands)

    Buizer - Voskamp, J.E.

    2011-01-01

    Introduction: Schizophrenia is a debilitating psychiatric disorder with a life-time risk of 0.46 – 1% in the general population. It is characterized by psychotic symptoms, including delusions and hallucinations. Its predisposition is influenced by a complex interaction of genetic and environmental

  7. European recommendations for primary prevention of congenital anomalies: A joined effort of EUROCAT and EUROPLAN projects to facilitate inclusion of this topic in the National Rare Disease Plans

    DEFF Research Database (Denmark)

    Taruscio, Domenica; Arriola, Larraitz; Baldi, Francesca

    2014-01-01

    Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention t...

  8. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

    NARCIS (Netherlands)

    Festen, E. A. M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefebvre, C.; Brant, S. R.; Cho, J. H.; Silverberg, M. S.; Taylor, K. D.; de Jong, D. J.; Stokkers, P. C.; Mcgovern, D.; Palmieri, O.; Achkar, J-P; Xavier, R. J.; Daly, M. J.; Duerr, R. H.; Wijmenga, C.; Weersma, R. K.; Rioux, J. D.

    Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac

  9. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

    NARCIS (Netherlands)

    Festen, E.A.M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefèbvre, C.; Brant, S.R.; Cho, J.H.; Silverberg, M.S.; Taylor, K.D.; de Jong, D.J.; Stokkers, P.C.; Mcgovern, D.; Palmieri, O.; Achkar, J.P.; Xavier, R.J.; Daly, M.J.; Duerr, R.H.; Wijmenga, C.; Weersma, R.K.; Rioux, J.D.

    2009-01-01

    Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac

  10. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis.

    NARCIS (Netherlands)

    Festen, E.A.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefebvre, C.; Brant, S.R.; Cho, J.H.; Silverberg, M.S.; Taylor, K.D.; Jong, D.J. de; Stokkers, P.C.; Mcgovern, D.; Palmieri, O.; Achkar, J.P.; Xavier, R.J.; Daly, M.J.; Duerr, R.H.; Wijmenga, C.; Weersma, R.K.; Rioux, J.D.

    2009-01-01

    OBJECTIVES: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac

  11. Shotgun metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome

    DEFF Research Database (Denmark)

    Xie, Hailiang; Guo, Ruijin; Zhong, Huanzi

    2016-01-01

    The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing...... have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those...... associated with diseases. Moreover, we identified 8 million SNPs in the gut microbiome and observe a high similarity in microbiome SNPs between twins that slowly decreases after decades of living apart. The results shed new light on the genetic and environmental influences on the composition and function...

  12. Broad Bandwidth or High Fidelity? Evidence from the Structure of Genetic and Environmental Effects on the Facets of the Five Factor Model

    Science.gov (United States)

    Briley, Daniel A.; Tucker-Drob, Elliot M.

    2017-01-01

    The Five Factor Model (FFM) of personality is well-established at the phenotypic level, but much less is known about the coherence of the genetic and environmental influences within each personality domain. Univariate behavioral genetic analyses have consistently found the influence of additive genes and nonshared environment on multiple personality facets, but the extent to which genetic and environmental influences on specific facets reflect more general influences on higher order factors is less clear. We applied a multivariate quantitative-genetic approach to scores on the CPI-Big Five facets for 490 monozygotic and 317 dizygotic twins who took part in the National Merit Twin Study. Our results revealed a complex genetic structure for facets composing all five factors, with both domain-general and facet-specific genetic and environmental influences. Models that required common genetic and environmental influences on each facet to occur by way of effects on a higher order trait did not fit as well as models allowing for common genetic and environmental effects to act directly on the facets for three of the Big Five domains. These results add to the growing body of literature indicating that important variation in personality occurs at the facet level which may be overshadowed by aggregating to the trait level. Research at the facet level, rather than the factor level, is likely to have pragmatic advantages in future research on the genetics of personality. PMID:22695681

  13. Environmental, phenotypic and genetic variation of wild barley (Hordeum spontaneum) from Israel

    NARCIS (Netherlands)

    Vanhala, T.; Rijn, C.P.E.; Buntjer, J.; Stam, P.; Nevo, E.; Poorter, H.; Eeuwijk, van F.A.

    2004-01-01

    Wild relatives of crop plants offer an attractive gene pool for cultivar improvement. We evaluated genetic and phenotypic variation for a set of 72 Israeli accessions of wild barley from 21 populations. These populations were grouped further into four ecotypes. In addition, environmental variables

  14. Genetic and Familial Environmental Effects on Suicide - An Adoption Study of Siblings

    DEFF Research Database (Denmark)

    Petersen, Liselotte; Sørensen, Thorkild I.A.; Andersen, Per Kragh

    2013-01-01

    While there is clear evidence of familial influences on suicide, the origin of these is less certain. We have investigated genetic and familial environmental factors by studying the occurrence of suicide in biological and adoptive siblings of adoptees who died by suicide compared to siblings...

  15. Socially related fears following exposure to trauma: environmental and genetic influences.

    Science.gov (United States)

    Collimore, Kelsey C; Asmundson, Gordon J G; Taylor, Steven; Jang, Kerry L

    2009-03-01

    Few studies have examined why socially related fears and posttraumatic stress commonly, but not invariably, co-occur. It may be that only traumata of human agency (e.g., sexual assault), for which there is an interpersonal component, give rise to co-occurring socially related fears. These symptoms might also co-occur because of shared genetic factors. We investigated these issues using a sample of 882 monozygotic and dizygotic twins. No significant differences in socially related fear (i.e., fear of negative evaluation, fear of socially observable arousal symptoms) were found between participants reporting assaultive or nonassaultive trauma. However, significant differences in socially related fear were found when participants were grouped into probable PTSD and no PTSD groups. Participants with probable PTSD exhibited greater socially related fear (i.e., fear of negative evaluation) than those without PTSD. Using biometric structural equation modeling, trauma exposure was best explained by shared and nonshared environmental influences. The fear of socially observable arousal symptoms was influenced by genetic and nonshared environmental influences. Implications and directions for future research are discussed.

  16. Clinical and Genetic Characterization of Patients with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Caused by a Plakophilin-2 Splice Mutation

    NARCIS (Netherlands)

    van der Smagt, Jasper J.; van der Zwaag, Paul A.; van Tintelen, J. Peter; Cox, Moniek G. P. J.; Wilde, Arthur A. M.; van Langen, Irene M.; Ummels, Amber; Hennekam, F. A. M.; Dooijes, Dennis; Gerbens, Frans; Bikker, Hennie; Hauer, Richard N. W.; Doevendans, Pieter A.

    2012-01-01

    Objectives: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by fibrofatty replacement of cardiomyocytes. In around 50% of index patients, a genetic predisposition is demonstrated. The purpose of this study was to examine a plakophilin-2 (PKP2) splice site

  17. Androgenetic Alopecia: Identification of Four Genetic Risk Loci and Evidence for the Contribution of WNT Signaling to Its Etiology

    NARCIS (Netherlands)

    Heilmann, S.; Kiefer, A.K.; Fricker, N.; Drichel, D.; Hillmer, A.M.; Herold, C.; Tung, J.Y.; Eriksson, N.; Redler, S.; Betz, R.C.; Li, R.; Karason, A.; Nyholt, D.R.; Song, K.; Vermeulen, S.; Kanoni, S.; Dedoussis, G.; Martin, N.G.; Kiemeney, L.A.L.M.; Mooser, V.; Stefansson, K.; Richards, J.B.; Becker, T.; Brockschmidt, F.F.; Hinds, D.A.; Nothen, M.M.

    2013-01-01

    The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are

  18. Added value measures in education show genetic as well as environmental influence.

    Science.gov (United States)

    Haworth, Claire M A; Asbury, Kathryn; Dale, Philip S; Plomin, Robert

    2011-02-02

    Does achievement independent of ability or previous attainment provide a purer measure of the added value of school? In a study of 4000 pairs of 12-year-old twins in the UK, we measured achievement with year-long teacher assessments as well as tests. Raw achievement shows moderate heritability (about 50%) and modest shared environmental influences (25%). Unexpectedly, we show that for indices of the added value of school, genetic influences remain moderate (around 50%), and the shared (school) environment is less important (about 12%). The pervasiveness of genetic influence in how and how much children learn is compatible with an active view of learning in which children create their own educational experiences in part on the basis of their genetic propensities.

  19. Human genetics of infectious diseases: between proof of principle and paradigm.

    Science.gov (United States)

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-09-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proof of principle that infectious diseases may result from various types of inborn errors of immunity, the genetic determinism of most infectious diseases in most patients remains unclear. However, in the future, studies in human genetics are likely to establish a new paradigm for infectious diseases.

  20. Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

    Directory of Open Access Journals (Sweden)

    Neragi-Miandoab Siyamek

    2008-01-01

    Full Text Available Abstract Malignant pleural mesothelioma (MPM is a rare, aggressive tumor for which no effective therapy exists despite the discovery of many possible molecular and genetic targets. Many risk factors for MPM development have been recognized including environmental exposures, genetic susceptibility, viral contamination, and radiation. However, the late stage of MPM diagnosis and the long latency that exists between some exposures and diagnosis have made it difficult to comprehensively evaluate the role of risk factors and their downstream molecular effects. In this review, we discuss the current molecular and genetic contributors in MPM pathogenesis and the risk factors associated with these carcinogenic processes.

  1. Genetic and Environmental Influences on the Mental Health of Children: A Twin Study.

    Science.gov (United States)

    Yin, Ping; Hou, Xiao; Qin, Qing; Deng, Wei; Hu, Hua; Luo, Qinghua; Du, Lian; Qiu, Haitang; Qiu, Tian; Fu, Yixiao; Meng, Huaqing; Li, Tao

    2016-08-01

    The current study explored the influences of genetic and environmental factors on the mental health of twins between ages 6 and 16. A total of 41 monozygotic (MZ) twins and 35 dizygotic twins were recruited. The psychological attributes and environmental information of children were evaluated. A significant correlation was found between twins in the diagnostic categories of any psychiatric disorder and attention deficit/hyperactivity disorder (ADHD)/hyperkinesis based on the Strengths and Difficulties Questionnaire scale in MZ twins. Furthermore, fathers' authoritarian parenting style was positively correlated with the probability of any psychiatric disorders and oppositional/conduct disorders, whereas mothers' authoritative parenting style was negatively correlated with the probability of any psychiatric disorders and ADHD/hyperkinesis. The probability of emotional disorders was negatively correlated with scores on the Stressful Life Events Scale. These results collectively suggest that genetic and environmental elements, such as parental rearing style and stressful life events, may influence children's mental health. [Journal of Psychosocial Nursing and Mental Health Services, 54(8), 29-34.]. Copyright 2016, SLACK Incorporated.

  2. Empathy in early childhood: genetic, environmental, and affective contributions.

    Science.gov (United States)

    Knafo, Ariel; Zahn-Waxler, Carolyn; Davidov, Maayan; Van Hulle, Carol; Robinson, JoAnn L; Rhee, Soo Hyun

    2009-06-01

    We investigated the genetic and environmental origins of children's empathy toward a distress victim and its correlates with emotional symptoms and affective knowledge. The cognitive (hypothesis testing) and affective (empathic concern) empathy of 122 twin pairs in response to simulated pain by an adult examiner was observed at 3.5 years of age. Moderate (0.19 to 0.44) heritabilities were estimated for individual differences in empathy, and the nonshared environment and error accounted for the rest of the variance. Hypothesis testing and empathic concern were moderately correlated, mainly through overlapping genetic effects. Although children's affective knowledge did not correlate with their empathy, affective knowledge interacted with mother-rated emotional symptoms in predicting empathy; knowledge about emotions was associated with greater empathy in children low in emotional symptoms. In contrast, among children with high degrees of emotional symptoms, those with better affective knowledge tended to show lower empathy.

  3. Cancer Screening and Genetics: A Tale of Two Paradigms

    OpenAIRE

    Hamilton, Jada G.; Edwards, Heather M.; Khoury, Muin J.; Taplin, Stephen H.

    2014-01-01

    The long-standing medical tradition to “first do no harm” is reflected in population-wide evidence-based recommendations for cancer screening tests that focus primarily on reducing morbidity and mortality. The conventional cancer screening process is predicated on finding early-stage disease that can be treated effectively; yet emerging genetic and genomic testing technologies have moved the target earlier in the disease development process to identify a probabilistic predisposition to diseas...

  4. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Directory of Open Access Journals (Sweden)

    Abigail R Dowling

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  5. Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility.

    Science.gov (United States)

    Dowling, Abigail R; Nedorezov, Laura B; Qiu, Xiaoliang; Marino, Joseph S; Hill, Jennifer W

    2013-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. The syndrome is caused by a combination of environmental influences and genetic predisposition. Despite extensive efforts, the heritable factors contributing to PCOS development are not fully understood. The objective of this study was to test the hypothesis that genetic background contributes to the development of a PCOS-like reproductive and metabolic phenotype in mice exposed to excess DHEA during the pubertal transition. We tested whether the PCOS phenotype would be more pronounced on the diabetes-prone C57BL/6 background than the previously used strain, BALB/cByJ. In addition, we examined strain-dependent upregulation of the expression of ovarian and extra-ovarian candidate genes implicated in human PCOS, genes containing known strain variants, and genes involved with steroidogenesis or insulin sensitivity. These studies show that there are significant strain-related differences in metabolic response to excess androgen exposure during puberty. Additionally, our results suggest the C57BL/6J strain provides a more robust and uniform experimental platform for PCOS research than the BALB/cByJ strain.

  6. Gender Differences and Effect of Air Pollution on Asthma in Children with and without Allergic Predisposition: Northeast Chinese Children Health Study

    Science.gov (United States)

    Dong, Guang-Hui; Chen, Tao; Liu, Miao-Miao; Wang, Da; Ma, Ya-Nan; Ren, Wan-Hui; Lee, Yungling Leo; Zhao, Ya-Dong; He, Qin-Cheng

    2011-01-01

    Background Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship. Methodology/Principal Findings 30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxides (NO2), ozone (O3) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM10, SO2, NO2, O3, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM10 (ORs = 1.36 per 31 µg/m3; 95% CI, 1.08–1.72), SO2 (ORs = 1.38 per 21 µg/m3; 95%CI, 1.12–1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO2 (ORs = 1.48 per 21 µg/m3; 95%CI, 1.21–1.80), NO2 (ORs = 1.26 per 10 µg/m3; 95%CI, 1.01–1.56), and current asthma with O3 (ORs = 1

  7. Is testicular dysgenesis syndrome a genetic, endocrine, or environmental disease, or an unexplained reproductive disorder?

    Science.gov (United States)

    Xing, Jian-Sheng; Bai, Zhi-Ming

    2018-02-01

    Progressive increases in the incidence of male reproductive disorders inclusive of hypospadias, cryptorchidism, poor semen quality, and testicular germ cell cancer (TGCC) have been observed in recent times. The central hypothesis of this study asserted that these disorders may all collectively signify testicular dysgenesis syndrome (TDS). This review aimed to provide evidence verifying the reality of TDS based on four key aspects: environmental endocrine-disrupting chemicals (EDCs), genetic factors, intrauterine growth disorders and lifestyle factors. Although TDS might result from genetic polymorphisms or aberration, recent evidence has highlighted links indicating the conditions associations to both environmental and lifestyle factors due to the rapid temporal changes in the clinical symptoms observed over recent decades. Based on our review of genetic and environmental factors, a key observation of our study suggested that there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. At present, current research has yet to elucidate the mechanisms of TDS, in addition to the lack of genuine consideration of a variety of potentially key factors and TDS mechanisms. In conclusion, our study revealed that environmental exposures owing to modern lifestyles are primary factors involved in the associated trends of the syndrome, which are capable of affecting the adult endocrine system via direct means or through epigenetic mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. The Perceived Reality of Television and Aggressive Predispositions Among Children in Mexico.

    Science.gov (United States)

    Korzenny, Felipe

    The purpose of this study was to assess the effectiveness of several independent variables in predicting the perception of television's content as real. The relationship between the perception of television violence as real and agressive predispositions of young viewers was analyzed. Two hundred seventy-three Mexican children in the third and…

  9. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis

    NARCIS (Netherlands)

    Festen, E. A. M.; Goyette, P.; Scott, R.; Annese, V.; Zhernakova, A.; Lian, J.; Lefèbvre, C.; Brant, S. R.; Cho, J. H.; Silverberg, M. S.; Taylor, K. D.; de Jong, D. J.; Stokkers, P. C.; Mcgovern, D.; Palmieri, O.; Achkar, J.-P.; Xavier, R. J.; Daly, M. J.; Duerr, R. H.; Wijmenga, C.; Weersma, R. K.; Rioux, J. D.

    2009-01-01

    Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1

  10. Characterisation of adaptive genetic diversity in environmentally contrasted populations of Eucalyptus camaldulensis Dehnh. (river red gum.

    Directory of Open Access Journals (Sweden)

    Shannon Dillon

    Full Text Available As an increasing number of ecosystems face departures from long standing environmental conditions under climate change, our understanding of the capacity of species to adapt will become important for directing conservation and management of biodiversity. Insights into the potential for genetic adaptation might be gained by assessing genomic signatures of adaptation to historic or prevailing environmental conditions. The river red gum (Eucalyptus camaldulensis Dehnh. is a widespread Australian eucalypt inhabiting riverine and floodplain habitats which spans strong environmental gradients. We investigated the effects of adaptation to environment on population level genetic diversity of E. camaldulensis, examining SNP variation in candidate gene loci sampled across 20 climatically diverse populations approximating the species natural distribution. Genetic differentiation among populations was high (F(ST = 17%, exceeding previous estimates based on neutral markers. Complementary statistical approaches identified 6 SNP loci in four genes (COMT, Dehydrin, ERECTA and PIP2 which, after accounting for demographic effects, exhibited higher than expected levels of genetic differentiation among populations and whose allelic variation was associated with local environment. While this study employs but a small proportion of available diversity in the eucalyptus genome, it draws our attention to the potential for application of wide spread eucalypt species to test adaptive hypotheses.

  11. Disease and genetic contributions toward local tissue volume disturbances in schizophrenia: a tensor-based morphometry study.

    Science.gov (United States)

    Yang, Yaling; Nuechterlein, Keith H; Phillips, Owen R; Gutman, Boris; Kurth, Florian; Dinov, Ivo; Thompson, Paul M; Asarnow, Robert F; Toga, Arthur W; Narr, Katherine L

    2012-09-01

    Structural brain deficits, especially frontotemporal volume reduction and ventricular enlargement, have been repeatedly reported in patients with schizophrenia. However, it remains unclear whether brain structural deformations may be attributable to disease-related or genetic factors. In this study, the structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 65 first-degree nonpsychotic relatives of schizophrenia patients, 27 community comparison (CC) probands, and 73 CC relatives were examined using tensor-based morphometry (TBM) to isolate global and localized differences in tissue volume across the entire brain between groups. We found brain tissue contractions most prominently in frontal and temporal regions and expansions in the putamen/pallidum, and lateral and third ventricles in schizophrenia patients when compared with unrelated CC probands. Results were similar, though less prominent when patients were compared with their nonpsychotic relatives. Structural deformations observed in unaffected patient relatives compared to age-similar CC relatives were suggestive of schizophrenia-related genetic liability and were pronounced in the putamen/pallidum and medial temporal regions. Schizophrenia and genetic liability effects for the putamen/pallidum were confirmed by regions-of-interest analysis. In conclusion, TBM findings complement reports of frontal, temporal, and ventricular dysmorphology in schizophrenia and further indicate that putamen/pallidum enlargements, originally linked mainly with medication exposure in early studies, also reflect a genetic predisposition for schizophrenia. Thus, brain deformation profiles revealed in this study may help to clarify the role of specific genetic or environmental risk factors toward altered brain morphology in schizophrenia.

  12. Gender Differences in Marital Status Moderation of Genetic and Environmental Influences on Subjective Health.

    Science.gov (United States)

    Finkel, Deborah; Franz, Carol E; Horwitz, Briana; Christensen, Kaare; Gatz, Margaret; Johnson, Wendy; Kaprio, Jaako; Korhonen, Tellervo; Niederheiser, Jenae; Petersen, Inge; Rose, Richard J; Silventoinen, Karri

    2015-10-14

    From the IGEMS Consortium, data were available from 26,579 individuals aged 23 to 102 years on 3 subjective health items: self-rated health (SRH), health compared to others (COMP), and impact of health on activities (ACT). Marital status was a marker of environmental resources that may moderate genetic and environmental influences on subjective health. Results differed for the 3 subjective health items, indicating that they do not tap the same construct. Although there was little impact of marital status on variance components for women, marital status was a significant modifier of variance in all 3 subjective health measures for men. For both SRH and ACT, single men demonstrated greater shared and nonshared environmental variance than married men. For the COMP variable, genetic variance was greater for single men vs. married men. Results suggest gender differences in the role of marriage as a source of resources that are associated with subjective health.

  13. [Environmental and genetic variables related with alterations in language acquisition in early childhood].

    Science.gov (United States)

    Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

    2017-01-01

    A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

  14. Transmaternal bisphenol a exposure accelerates diabetes type 1 development in NOD mice

    NARCIS (Netherlands)

    Bodin, J.; Bølling, A.B.; Becher, R.; Kuper, F.; Løvik, M.; Nygaard, U.C.

    2014-01-01

    Diabetes mellitus type 1 is an autoimmune disease with a genetic predisposition that is triggered by environmental factors during early life. Epidemiological studies show that bisphenol A (BPA), an endocrine disruptor, has been detected in about 90% of all analyzed human urine samples. In this

  15. Socio-economic status, lifestyle and childhood obesity in Gombe ...

    African Journals Online (AJOL)

    Background: Childhood obesity is a complex condition resulting from an interplay of genetic predisposition, environmental factors and socio-economic status. The prevalence has been increasing all over the world, probably due to economic transition and rapid urbanization as well as globalisation. This relationship should ...

  16. Methylation, Lifestyle and Genes in the Pathogenesis and Prevention of Human Congenital Heart Diseases

    NARCIS (Netherlands)

    L.M.J.W. van Driel (Lydi)

    2009-01-01

    textabstractUp until now, only approximately 15% of the CHD can be attributed to a known cause. The remaining 85% is thought to result from interactions between genetic predispositions and periconception environmental exposures. Folate, a B vitamin involved in the one-carbon metabolism, has been

  17. Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

    DEFF Research Database (Denmark)

    Benyamin, B; Sørensen, T I A; Schousboe, K

    2007-01-01

    and environmental factors influencing this cluster in a general population of twin pairs. MATERIALS AND METHODS: A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. RESULTS: All......AIMS/HYPOTHESIS: The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic...... endophenotypes showed moderate to high heritability (0.31-0.69) and small cial environmental background...

  18. The structure of genetic and environmental risk factors for phobias in women.

    Science.gov (United States)

    Czajkowski, N; Kendler, K S; Tambs, K; Røysamb, E; Reichborn-Kjennerud, T

    2011-09-01

    To explore the genetic and environmental factors underlying the co-occurrence of lifetime diagnoses of DSM-IV phobia. Female twins (n=1430) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime specific phobia, social phobia and agoraphobia. Comorbidity between the phobias were assessed by odds ratios (ORs) and polychoric correlations and multivariate twin models were fitted in Mx. Phenotypic correlations of lifetime phobia diagnoses ranged from 0.55 (agoraphobia and social phobia, OR 10.95) to 0.06 (animal phobia and social phobia, OR 1.21). In the best fitting twin model, which did not include shared environmental factors, heritability estimates for the phobias ranged from 0.43 to 0.63. Comorbidity between the phobias was accounted for by two common liability factors. The first loaded principally on animal phobia and did not influence the complex phobias (agoraphobia and social phobia). The second liability factor strongly influenced the complex phobias, but also loaded weak to moderate on all the other phobias. Blood phobia was mainly influenced by a specific genetic factor, which accounted for 51% of the total and 81% of the genetic variance. Phobias are highly co-morbid and heritable. Our results suggest that the co-morbidity between phobias is best explained by two distinct liability factors rather than a single factor, as has been assumed in most previous multivariate twin analyses. One of these factors was specific to the simple phobias, while the other was more general. Blood phobia was mainly influenced by disorder specific genetic factors.

  19. Environmental Contamination Genetic Consequences Monitoring on the Former Semipalatinsk Test Site: General Approach

    International Nuclear Information System (INIS)

    Seisebaev, A.T.; Bakhtin, M.M.; Zhapbasov, R.Zh.

    1998-01-01

    For an objective assessment of nuclear test consequences for the environment it is necessary, together with the investigation of radiation situation, to study live biological systems, particularly the genetic effects of chronic ionizing radiation. The long staying of plants and animals on the territories with the elevated radiation background level can lead to the change of organism genetic system. In this connection the monitoring of chronically exposed natural populations is of particular interest and can serve as the objective indicator of the scale of natural biota genetic damage. Basing on the results obtained during plant and animal studies one can indirectly assess the hazard of people genetic damage. Besides, studying the mutational process on natural populations exposed to the chronic ionizing radiation one can reveal new regularities, which are impossible to be detected in the laboratory conditions, and new aspects of radiation genetics. The issue of radiation adaptation of organisms affected by the various doses of ionizing radiation is very acute. The prerequisite of organism adaptation to the certain radiation background is genetic heterogeneity of individuals comprising the population and selection of radiation-induced individuals, which are the carriers of the mutation of high radioresistance. The uniqueness of the Semipalatinsk Test site and the necessity of long-term investigations of the nuclear test consequences for the environment demand the elaboration of principles for organization and utilization of natural population genetic monitoring. Radiation-genetic monitoring is the long-term observation of palpitation gene pool conditions, assessment and forecast of their spatial and time alteration, determination of limits of changes admitted under the condition of environmental radioactive contamination. It includes a series of the main research directions and has quite certain methodological peculiarities. In this paper we discuss the tasks of

  20. Environmental gradients predict the genetic population structure of a coral reef fish in the Red Sea

    KAUST Repository

    Nanninga, Gerrit B.

    2014-01-20

    The relatively recent fields of terrestrial landscape and marine seascape genetics seek to identify the influence of biophysical habitat features on the spatial genetic structure of populations or individuals. Over the last few years, there has been accumulating evidence for the effect of environmental heterogeneity on patterns of gene flow and connectivity in marine systems. Here, we investigate the population genetic patterns of an anemonefish, Amphiprion bicinctus, along the Saudi Arabian coast of the Red Sea. We collected nearly one thousand samples from 19 locations, spanning approximately 1500 km, and genotyped them at 38 microsatellite loci. Patterns of gene flow appeared to follow a stepping-stone model along the northern and central Red Sea, which was disrupted by a distinct genetic break at a latitude of approximately 19°N. The Red Sea is characterized by pronounced environmental gradients along its axis, roughly separating the northern and central from the southern basin. Using mean chlorophyll-a concentrations as a proxy for this gradient, we ran tests of isolation by distance (IBD, R2 = 0.52) and isolation by environment (IBE, R2 = 0.64), as well as combined models using partial Mantel tests and multiple matrix regression with randomization (MMRR). We found that genetic structure across our sampling sites may be best explained by a combined model of IBD and IBE (Mantel: R2 = 0.71, MMRR: R2 = 0.86). Our results highlight the potential key role of environmental patchiness in shaping patterns of gene flow in species with pelagic larval dispersal. We support growing calls for the integration of biophysical habitat characteristics into future studies of population genetic structure. © 2014 John Wiley & Sons Ltd.

  1. Environmental gradients predict the genetic population structure of a coral reef fish in the Red Sea

    KAUST Repository

    Nanninga, Gerrit B.; Saenz Agudelo, Pablo; Manica, Andrea; Berumen, Michael L.

    2014-01-01

    The relatively recent fields of terrestrial landscape and marine seascape genetics seek to identify the influence of biophysical habitat features on the spatial genetic structure of populations or individuals. Over the last few years, there has been accumulating evidence for the effect of environmental heterogeneity on patterns of gene flow and connectivity in marine systems. Here, we investigate the population genetic patterns of an anemonefish, Amphiprion bicinctus, along the Saudi Arabian coast of the Red Sea. We collected nearly one thousand samples from 19 locations, spanning approximately 1500 km, and genotyped them at 38 microsatellite loci. Patterns of gene flow appeared to follow a stepping-stone model along the northern and central Red Sea, which was disrupted by a distinct genetic break at a latitude of approximately 19°N. The Red Sea is characterized by pronounced environmental gradients along its axis, roughly separating the northern and central from the southern basin. Using mean chlorophyll-a concentrations as a proxy for this gradient, we ran tests of isolation by distance (IBD, R2 = 0.52) and isolation by environment (IBE, R2 = 0.64), as well as combined models using partial Mantel tests and multiple matrix regression with randomization (MMRR). We found that genetic structure across our sampling sites may be best explained by a combined model of IBD and IBE (Mantel: R2 = 0.71, MMRR: R2 = 0.86). Our results highlight the potential key role of environmental patchiness in shaping patterns of gene flow in species with pelagic larval dispersal. We support growing calls for the integration of biophysical habitat characteristics into future studies of population genetic structure. © 2014 John Wiley & Sons Ltd.

  2. Genetic and Environmental Sources of Implicit and Explicit Self-Esteem and Affect: Results from a Genetically Sensitive Multi-group Design.

    Science.gov (United States)

    Stieger, Stefan; Kandler, Christian; Tran, Ulrich S; Pietschnig, Jakob; Voracek, Martin

    2017-03-01

    In today's world, researchers frequently utilize indirect measures of implicit (i.e., automatic, spontaneous) evaluations. The results of several studies have supported the usefulness of these measures in predicting behavior, as compared to utilizing direct measures of explicit (i.e., purposeful, deliberate) evaluations. A current, under-debate issue concerns the origin of these implicit evaluations. The present genetically sensitive multi-group study analyzed data from 223 twin pairs and 222 biological core families to estimate possible genetic and environmental sources of individual differences in implicit and explicit self-esteem and affect. The results show that implicit self-esteem and affect maintain a substantial genetic basis, but demonstrate little influence from the shared environment by siblings (e.g., shared familial socialization in childhood). A bivariate analysis found that implicit and explicit evaluations of the same construct share a common genetic core which aligns with the motivation and opportunity as determinants (MODE) model.

  3. Epigenetic changes in neurology: DNA methylation in multiple sclerosis.

    Science.gov (United States)

    Iridoy Zulet, M; Pulido Fontes, L; Ayuso Blanco, T; Lacruz Bescos, F; Mendioroz Iriarte, M

    2017-09-01

    Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Genetic predisposition to hemophagocytic lymphohistiocytosis: Report on 500 patients from the Italian registry

    OpenAIRE

    Cetica, Valentina; Sieni, Elena; Pende, Daniela; Danesino, Cesare; De Fusco, Carmen; Locatelli, Franco; Micalizzi, Concetta; Putti, Maria Caterina; Biondi, Andrea; Fagioli, Franca; Moretta, Lorenzo; Griffiths, Gillian M.; Luzzatto, Lucio; Aric?, Maurizio

    2016-01-01

    Background Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease affecting mostly children but also adults and characterized by hyperinflammatory features. A subset of patients, referred to as having familial hemophagocytic lymphohistiocytosis (FHL), have various underlying genetic abnormalities, the frequencies of which have not been systematically determined previously. Objective This work aims to further our understanding of the pathogenic bases of this ra...

  5. Determinants of Excess Genetic Risk of Acute Myocardial Infarction - A Matched Case-Control Study

    Czech Academy of Sciences Publication Activity Database

    Valenta, Zdeněk; Mazura, Ivan; Kolář, M.; Feglarová, Petra; Peleška, Jan; Tomečková, Marie; Kalina, Jan; Slovák, Dalibor; Zvárová, Jana

    2012-01-01

    Roč. 8, č. 1 (2012), s. 34-43 ISSN 1801-5603 R&D Projects: GA MŠk(CZ) 1M06014 Institutional support: RVO:67985807 Keywords : genome-wide association study * gene expression * myocardial infarction * genetic predisposition * predictive modeling Subject RIV: BB - Applied Statistics, Operational Research http://www.ejbi.org/img/ejbi/2012/1/Valenta_en.pdf

  6. Unraveling the genetic architecture of environmental variance of somatic cell score using high-density single nucleotide polymorphism and cow data from experimental farms

    NARCIS (Netherlands)

    Mulder, H.A.; Crump, R.E.; Calus, M.P.L.; Veerkamp, R.F.

    2013-01-01

    In recent years, it has been shown that not only is the phenotype under genetic control, but also the environmental variance. Very little, however, is known about the genetic architecture of environmental variance. The main objective of this study was to unravel the genetic architecture of the mean

  7. Genetic and environmental influences on the relationships between family connectedness, school connectedness, and adolescent depressed mood: sex differences.

    Science.gov (United States)

    Jacobson, K C; Rowe, D C

    1999-07-01

    This study investigated (a) genetic and environmental contributions to the relationship between family and school environment and depressed mood and (b) potential sex differences in genetic and environmental contributions to both variation in and covariation between family connectedness, school connectedness, and adolescent depressed mood. Data are from 2,302 adolescent sibling pairs (mean age = 16 years) who were part of the National Longitudinal Study of Adolescent Health. Although genetic factors appeared to be important overall, model-fitting analyses revealed that the best-fitting model was a model that allowed for different parameters for male and female adolescents. Genetic contributions to variation in all 3 variables were greater among female adolescents than male adolescents, especially for depressed mood. Genetic factors also contributed to the correlations between family and school environment and adolescent depressed mood, although, again, these factors were stronger for female than for male adolescents.

  8. Interactions between environmental factors and maternal-fetal genetic variations: strategies to elucidate risks of preterm birth.

    Science.gov (United States)

    Pereyra, Silvana; Bertoni, Bernardo; Sapiro, Rossana

    2016-07-01

    Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB. The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational ageenvironmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. Interactions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of

  9. Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of FOXO3 Variations.

    Directory of Open Access Journals (Sweden)

    Liang Sun

    Full Text Available Glucose homeostasis is a trait of healthy ageing and is crucial to the elderly, but less consideration has been given to the age composition in most studies involving genetics and hyperglycemia.Seven variants in FOXO3 were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 ± 3.6, 45.9 ± 8.2 and 46.8 ± 10.3, respectively to compare the contribution of FOXO3 to fasting hyperglycemia (FH between long-lived individuals (LLI, aged over 90 years and middle-aged subjects (aged from 35-65 years.A different genetic predisposition of FOXO3 alleles to FH was observed between LLI and both of two middle-aged cohorts. In the LLI cohort, the longevity beneficial alleles of three variants with the haplotype "AGGC" in block 1 were significantly protective to FH, fasting glucose, hemoglobin A1C and HOMA-IR. Notably, combining multifactor dimensionality reduction and logistic regression, we identified a significant 3-factor interaction model (rs2802288, rs2802292 and moderate physical activity associated with lower FH risk. However, not all of the findings were replicated in the two middle-aged cohorts.Our data provides a novel insight into the inconsistent genetic determinants between middle-aged and LLI subjects. FOXO3 might act as a shared genetic predisposition to hyperglycemia and lifespan.

  10. Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of FOXO3 Variations.

    Science.gov (United States)

    Sun, Liang; Hu, Caiyou; Qian, Yu; Zheng, Chenguang; Liang, Qinghua; Lv, Zeping; Huang, Zezhi; Qi, Keyan; Huang, Jin; Zhou, Qin; Yang, Ze

    2015-01-01

    Glucose homeostasis is a trait of healthy ageing and is crucial to the elderly, but less consideration has been given to the age composition in most studies involving genetics and hyperglycemia. Seven variants in FOXO3 were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 ± 3.6, 45.9 ± 8.2 and 46.8 ± 10.3, respectively) to compare the contribution of FOXO3 to fasting hyperglycemia (FH) between long-lived individuals (LLI, aged over 90 years) and middle-aged subjects (aged from 35-65 years). A different genetic predisposition of FOXO3 alleles to FH was observed between LLI and both of two middle-aged cohorts. In the LLI cohort, the longevity beneficial alleles of three variants with the haplotype "AGGC" in block 1 were significantly protective to FH, fasting glucose, hemoglobin A1C and HOMA-IR. Notably, combining multifactor dimensionality reduction and logistic regression, we identified a significant 3-factor interaction model (rs2802288, rs2802292 and moderate physical activity) associated with lower FH risk. However, not all of the findings were replicated in the two middle-aged cohorts. Our data provides a novel insight into the inconsistent genetic determinants between middle-aged and LLI subjects. FOXO3 might act as a shared genetic predisposition to hyperglycemia and lifespan.

  11. Frequent respiratory tract infections in children. The role of environmental and genetic factors.

    NARCIS (Netherlands)

    Ruskamp, J.M.

    2009-01-01

    Respiratory tract infections (RTI), presenting as common cold, pharyngitis, tonsillitis, acute otitis media, bronchitis or pneumonia are a major health problem in children. In this thesis common environmental and host factors, as well as plausible genetic factors were evaluated in a large birth

  12. Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

    NARCIS (Netherlands)

    Bodin, J.; Kocbach Bølling, A.; Wendt, A.; Eliasson, L.; Becher, R.; Kuper, F.; Løvik, M.; Nygaard, U.C.

    2015-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese

  13. The RadGenomics project. Prediction for radio-susceptibility of individuals with genetic predisposition

    International Nuclear Information System (INIS)

    Imai, Takashi

    2003-01-01

    The ultimate goal of our project, named RadGenomics, is to elucidate the heterogeneity of the response to ionizing radiation arising from genetic variation among individuals, for the purpose of developing personalized radiation therapy regimens for cancer patients. Cancer patients exhibit patient-to-patient variability in normal tissue reactions after radiotherapy. Several observations support the hypothesis that the radiosensitivity of normal tissue is influenced by genetic factors. The rapid progression of human genome sequencing and the recent development of new technologies in molecular biology are providing new opportunities for elucidating the genetic basis of individual differences in susceptibility to radiation exposure. The development of a sufficiently robust, predictive assay enabling individual dose adjustment would improve the outcome of radiation therapy in patients. Our strategy for identification of DNA polymorphisms that contribute to the individual radiosensitivity is as follows. First, we have been categorizing DNA samples obtained from cancer patients, who have been kindly introduced to us through many collaborators, according to their clinical characteristics including the method and effect of treatment and side effects as scored by toxicity criteria, and also the result of an in vitro radiosensitivity assay, e.g., the micronuclei assay of their lymphocytes. Second, we have identified candidate genes for genotyping mainly by using our custom-designed oligonucleotide array with RNA samples, in which the probes were obtained from more than 40 cancer and 3 fibroblast cell lines whose radiosensitivity level was quite heterogeneous. We have also been studying the modification of proteins after irradiation of cells which may be caused by mainly phosphorylation or dephosphorylation, using mass spectrometry. Genes encoding the modified proteins and/or other proteins with which they interact such as specific protein kinases and phosphatases are also

  14. Human genetics of infectious diseases: between proof of principle and paradigm

    OpenAIRE

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-01-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proo...

  15. Incidence of environmental and genetic factors causing congenital cataract in Children of Lahore.

    Science.gov (United States)

    Naz, Shagufta; Sharif, Saima; Badar, Hafsa; Rashid, Farzana; Kaleem, Afshan; Iqtedar, Mehwish

    2016-07-01

    To check the incidence of environmental and genetic factors causing congenital cataract in infants. The descriptive study was conducted at Layton Rahmatullah Benevolent Trust, Lahore, Pakistan, from October 2013 to April 2014, and comprised children under 15 years of age who had rubella syndrome, herpes simplex, birth trauma, trisomy 21, Nance-Horan syndrome or Lowe's syndrome. Of the 38,000 cases examined, 120(0.3%) patients were diagnosed with congenital cataract. Of them, 52(43.33%)were aged between 2 and 5 years,22(18.33%) <11 years and 10(8.33%) ?15 years. Bilateral congenital cataract was observed in 91(75.83%) patients and unilateral congenital cataract in 29(24.17%). Environmental factors caused 72(62.07%) cases and genetic factors caused 44(37.93%).. Congenital cataract predominated in boys compared to girls. Early diagnosis and adequate therapy requires specific technology, as well as long-term and permanent care..

  16. Genetic and environmental influences on externalizing behavior and alcohol problems in adolescence: A female twin study

    Science.gov (United States)

    Knopik, Valerie S.; Heath, Andrew C.; Bucholz, Kathleen K.; Madden, Pamela A.F.; Waldron, Mary

    2009-01-01

    Genetic and environmental contributions to the observed correlations among DSM-IV ADHD problems [inattentive (INATT) and hyperactive/impulsive (HYP/IMP) behaviors], conduct problems (CDP) and alcohol problems (AlcProb) were examined by fitting multivariate structural equation models to data from the Missouri Adolescent Female Twin Study [N=2892 twins (831 monozygotic pairs, 615 dizygotic pairs)]. Based on results of preliminary regression models, we modified the structural model to jointly estimate (i) the regression of each phenotype on significant familial/prenatal predictors, and (ii) genetic and environmental contributions to the residual variance and covariance. Results suggested that (i) parental risk factors, such as parental alcohol dependence and regular smoking, increase risk for externalizing behavior; (ii) prenatal exposures predicted increased symptomatology for HYP/IMP (smoking during pregnancy), INATT and CDP (prenatal alcohol exposure); (iii) after adjusting for measured familial/prenatal risk factors, genetic influences were significant for HYP/IMP, INATT, and CDP; however, similar to earlier reports, genetic effects on alcohol dependence symptoms were negligible; and (iv) in adolescence, correlated liabilities for conduct and alcohol problems are found in environmental factors common to both phenotypes, while covariation among impulsivity, inattention, and conduct problems is primarily due to genetic influences common to these three behaviors. Thus, while a variety of adolescent problem behaviors are significantly correlated, the structure of that association may differ as a function of phenotype (e.g., comorbid HYP/IMP and CDP vs. comorbid CDP and AlcProb), a finding that could inform different approaches to treatment and prevention. PMID:19341765

  17. Are genetic and environmental influences on job satisfaction stable over time? A three-wave longitudinal twin study.

    Science.gov (United States)

    Li, Wen-Dong; Stanek, Kevin C; Zhang, Zhen; Ones, Deniz S; McGue, Matt

    2016-11-01

    Job satisfaction research has unfolded as an exemplary manifestation of the "person versus environment" debate in applied psychology. With the increasing recognition of the importance of time, it is informative to examine a question critical to the dispositional view of job satisfaction: Are genetic influences on job satisfaction stable across different time points? Drawing upon dispositional and situational perspectives on job satisfaction and recent research in developmental behavioral genetics, we examined whether the relative potency of genetic (i.e., the person) and environmental influences on job satisfaction changed over time in a 3-wave longitudinal twin study. Biometric behavioral genetics analyses showed that genetic influences accounted for 31.2% of the variance in job satisfaction measured at approximately Age 21, which was markedly greater than the 18.7% and 19.8% of variance explained by genetic factors at Age 25 and Age 30. Such genetic influences were mediated via positive affectivity and negative affectivity, but not via general mental ability. After partialing out genetic influences, environmental influences on job satisfaction were related to interpersonal conflict at work and occupational status, and these influences were relatively stable across the 3 time points. These results offer important implications for organizations and employees to better understand and implement practices to enhance job satisfaction. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. Differential response of rat strains to obesogenic diets underlines the importance of genetic makeup of an individual towards obesity.

    Science.gov (United States)

    Mn, Muralidhar; Smvk, Prasad; Battula, Kiran Kumar; Nv, Giridharan; Kalashikam, Rajender Rao

    2017-08-22

    Obesity, a multifactorial disorder, results from a chronic imbalance of energy intake vs. expenditure. Apart from excessive consumption of high calorie diet, genetic predisposition also seems to be equally important for the development of obesity. However, the role of genetic predisposition in the etiology of obesity has not been clearly delineated. The present study addresses this problem by selecting three rat strains (WNIN, F-344, SD) with different genetic backgrounds and exposing them to high calorie diets. Rat strains were fed HF, HS, and HFS diets and assessed for physical, metabolic, biochemical, inflammatory responses, and mRNA expression. Under these conditions: significant increase in body weight, visceral adiposity, oxidative stress and systemic pro-inflammatory status; the hallmarks of central obesity were noticed only in WNIN. Further, they developed altered glucose and lipid homeostasis by exhibiting insulin resistance, impaired glucose tolerance, dyslipidemia and fatty liver condition. The present study demonstrates that WNIN is more prone to develop obesity and associated co-morbidities under high calorie environment. It thus underlines the cumulative role of genetics (nature) and diet (nurture) towards the development of obesity, which is critical for understanding this epidemic and devising new strategies to control and manage this modern malady.

  19. [Coronary heart disease: epidemiologic-genetic aspects].

    Science.gov (United States)

    Epstein, F H

    1985-01-01

    Coronary heart disease and the risk factors which predispose to it aggregate in families. How much of this clustering of disease is "explained" by the familial resemblance in predisposing factors? The published reports which bear on this question fall into six distinct study designs: prospective studies, persons at high or low risk or persons with and without a positive family history as points of departure, case-control studies, studies of patients who had a coronary angiogram and studies in different ethnic groups. The findings of the 16 investigations reviewed suggest that there are as yet unidentified factors - genetic, environmental or both - which are responsible for familial clustering of coronary heart disease, apart from the three main risk factors (serum lipids, blood pressure, smoking) and diabetes. Future research must put greater emphasis on studies of families rather than individuals and on closer collaboration between epidemiologists and geneticists, in order to fill these gaps in knowledge. It is likely that the individual predisposition to coronary heart disease is due in part to genetic influences which remain to be discovered in the course of such studies. They would help in identifying susceptible person in the population with greater precision than is now possible. The "high-risk strategy" of coronary heart disease prevention will become more efficient as more specific and sensitive tests of disease prediction are developed. In the meantime, preventive programmes must be put into action on the basis of what is already known, on the level of both the high-risk and the community-wide mass strategy.

  20. Genetic and environmental relationships between change in weight and insulin resistance: the Healthy Twin Study.

    Science.gov (United States)

    Song, Yun-Mi; Lee, Kayoung; Sung, Joohon

    2014-06-01

    We aimed to investigate the association between weight change from 20 years of age and insulin resistance (IR), and genetic and environmental relationships between these traits. In 594 Korean twins and family members (209 men, 385 women, 44.0 ± 10.8 years old), the percentage of weight change was calculated using self-reported body weight at 20 years of age and currently measured bodyweight. IR traits were assessed using fasting plasma glucose and insulin, the homeostasis model assessment of IR index (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI). Linear mixed analysis was applied after adjusting for household, body mass index (BMI) at the age of 20 years, age, sex, alcohol, smoking, physical activity, and caloric intake. Heritabilities and genetic and environmental correlations were estimated after adjusting for covariates. In 55 monozygotic twin pairs discordant for HOMA-IR level by >0.3, a conditional logistic regression analysis was conducted regarding weight change. Increases in glucose, insulin, and HOMA-IR and a decrease in QUICKI were associated with a higher percentage of weight change (p change since 20 years old, after adjusting for lifestyle-related factors. In conclusion, both genetic and environmental influences played significant roles in the positive association between weight change from 20 years of age and IR.

  1. Privacy and ethics in pediatric environmental health research-part I: genetic and prenatal testing.

    Science.gov (United States)

    Fisher, Celia B

    2006-10-01

    The pressing need for empirically informed public policies aimed at understanding and promoting children's health has challenged environmental scientists to modify traditional research paradigms and reevaluate their roles and obligations toward research participants. Methodologic approaches to children's environmental health research raise ethical challenges for which federal regulations may provide insufficient guidance. In this article I begin with a general discussion of privacy concerns and informed consent within pediatric environmental health research contexts. I then turn to specific ethical challenges associated with research on genetic determinants of environmental risk, prenatal studies and maternal privacy, and data causing inflicted insight or affecting the informational rights of third parties.

  2. Genetic and environmental influences on the transmission of parental depression to children’s depression and conduct disturbance: An extended Children of Twins study

    Science.gov (United States)

    Silberg, Judy L.; Maes, Hermine; Eaves, Lindon J.

    2010-01-01

    Background Despite the increased risk of depression and conduct problems in children of depressed parents, the mechanism by which parental depression affects their children’s behavioral and emotional functioning is not well understood. The present study was undertaken to determine whether parental depression represents a genuine environmental risk factor in children’s psychopathology, or whether children’s depression/conduct can be explained as a secondary consequence of the genetic liability transmitted from parents to their offspring. Methods Children of Twins (COT) data collected on 2,674 adult female and male twins, their spouses, and 2,940 of their children were used to address whether genetic and/or family environmental factors best account for the association between depression in parents and depression and conduct problems in their children. Data collected on juvenile twins from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) were also included to estimate child-specific genetic and environmental influences apart from those effects arising from the transmission of the parental depression itself. The fit of alternative Children of Twin models were evaluated using the statistical program Mx. Results The most compelling model for the association between parental and juvenile depression was a model of direct environmental risk. Both family environmental and genetic factors accounted for the association between parental depression and child conduct disturbance. Conclusions These findings illustrate how a genetically mediated behavior such as parental depression can have both an environmental and genetic impact on children’s behavior. We find developmentally specific genetic factors underlying risk to juvenile and adult depression. A shared genetic liability influence both parental depression and juvenile conduct disturbance, implicating child CD as an early indicator of genetic risk for depression in adulthood. In summary, our

  3. Genetic and Environmental Influences on Affiliation with Deviant Peers during Adolescence and Early Adulthood

    OpenAIRE

    Tarantino, Nicholas; Tully, Erin C.; Garcia, Sarah E.; South, Susan; Iacono, William G.; McGue, Matt

    2013-01-01

    Adolescence and early adulthood is a time when peer groups become increasingly influential in the lives of young people. Youth exposed to deviant peers risk susceptibility to externalizing behaviors and related psychopathology. In addition to environmental correlates of deviant peer affiliation, a growing body of evidence suggests that affiliation with deviant peers is heritable. This study examined the magnitude of genetic and environmental influences on affiliation with deviant peers, chang...

  4. Family environmental factors influencing the developing behavioral controls of food intake and childhood overweight.

    Science.gov (United States)

    Birch, L L; Davison, K K

    2001-08-01

    Although a large body of research has assessed direct genetic links between parent and child weight status, relatively little research has assessed the extent to which parents (particularly parents who are overweight) select environments that promote overweight among their children. Parents provide food environments for their children's early experiences with food and eating. These family eating environments include parents' own eating behaviors and child-feeding practices. Results of the limited research on behavioral mediators of familial patterns of overweight indicate that parents' own eating behaviors and their parenting practices influence the development of children's eating behaviors, mediating familial patterns of overweight. In particular, parents who are overweight, who have problems controlling their own food intake, or who are concerned about their children's risk for overweight may adopt controlling child-feeding practices in an attempt to prevent overweight in their children. Unfortunately, research reveals that these parental control attempts may interact with genetic predispositions to promote the development of problematic eating styles and childhood overweight. Although the authors have argued that behavioral mediators of family resemblances in weight status, such as parents' disinhibited or binge eating and parenting practices are shaped largely by environmental factors, individual differences in these behaviors also have genetic bases. A primary public health goal should be the development of family-based prevention programs for childhood overweight. The findings reviewed here suggest that effective prevention programs must focus on providing anticipatory guidance on parenting to foster patterns of preference and food selection in children more consistent with healthy diets and promote children's ability to self-regulate intake. Guidance for parents should include information on how children develop patterns of food intake in the family context

  5. Whole-genome sequencing analysis of phenotypic heterogeneity and anticipation in Li-Fraumeni cancer predisposition syndrome.

    Science.gov (United States)

    Ariffin, Hany; Hainaut, Pierre; Puzio-Kuter, Anna; Choong, Soo Sin; Chan, Adelyne Sue Li; Tolkunov, Denis; Rajagopal, Gunaretnam; Kang, Wenfeng; Lim, Leon Li Wen; Krishnan, Shekhar; Chen, Kok-Siong; Achatz, Maria Isabel; Karsa, Mawar; Shamsani, Jannah; Levine, Arnold J; Chan, Chang S

    2014-10-28

    The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations. To address the genetic basis of phenotypic disparities of LFS/LFL, we performed whole-genome sequencing (WGS) of 13 subjects from two generations of an LFS kindred. Neither de novo CNV nor significant difference in total CNV was detected in relation with successive generations or with age at cancer onset. These observations were consistent with an experimental mouse model system showing that trp53 deficiency in the germ line of father or mother did not increase CNV occurrence in the offspring. On the other hand, individual records on 1,771 TP53 mutation carriers from 294 pedigrees were compiled to assess genetic anticipation patterns (International Agency for Research on Cancer TP53 database). No strictly defined anticipation pattern was observed. Rather, in multigeneration families, cancer onset was delayed in older compared with recent generations. These observations support an alternative model for apparent anticipation in which rare variants from noncarrier parents may attenuate constitutive resistance to tumorigenesis in the offspring of TP53 mutation carriers with late cancer onset.

  6. Clinical and genetic aspects of testicular germ cell tumours

    Directory of Open Access Journals (Sweden)

    Holzik Martijn

    2008-02-01

    Full Text Available Abstract In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs. TGCT is the most common type of malignant disorder in men aged 15-40 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.

  7. Clinical and genetic aspects of testicular germ cell tumours.

    Science.gov (United States)

    Lutke Holzik, Martijn F; Sijmons, Rolf H; Hoekstra-Weebers, Josette Ehm; Sleijfer, Dirk T; Hoekstra, Harald J

    2008-02-15

    In this paper we review clinical and genetic aspects of testicular germ cell tumours (TGCTs). TGCT is the most common type of malignant disorder in men aged 1540 years. Its incidence has increased sharply in recent years. Fortunately, survival of patients with TGCT has improved enormously, which can chiefly be attributed to the cisplatin-based polychemotherapy that was introduced in the nineteen eighties to treat patients with metastasized TGCT. In addition, new strategies have been developed in the surgical approach to metastasized/non-metastasized TGCT and alterations have been made to the radiotherapy technique and radiation dose for seminoma. Family history of TGCT is among the strongest risk factors for this tumour type. Although this fact and others suggest the existence of genetic predisposition to develop TGCT, no germline mutations conferring high risk of developing TGCT have been identified so far. A small deletion, referred to as gr/gr, identified on the Y chromosome is probably associated with only a modest increase in TGCT risk, and linkage of familial TGCT to the Xq27 region has not been confirmed yet. Whether highly penetrant TGCT-predisposing mutations truly exist or familial clustering of TGCT can be explained by combinations of weak predispositions, shared in utero or postnatal risks factors and coincidental somatic mutations is an intriguing puzzle, still waiting to be solved.

  8. The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives of Genetic Information.

    Science.gov (United States)

    Weaver, Meaghann

    2016-03-01

    Genetic testing reveals information about a patient's health status and predictions about the patient's future wellness, while also potentially disclosing health information relevant to other family members. With the increasing availability and affordability of genetic testing and the integration of genetics into mainstream medicine, the importance of clarifying the scope of confidentiality and the rules regarding disclosure of genetic findings to genetic relatives is prime. The United Nations International Declaration on Human Genetic Data urges an appreciation for principles of equality, justice, solidarity and responsibility in the context of genetic testing, including a commitment to honoring the privacy and security of the person tested. Considering this global mandate and recent professional statements in the context of a legal amendment to patient privacy policies in Australia, a fresh scrutiny of the legal history of a physician's duty to warn is warranted. This article inquiries whether there may be anything ethically or socially amiss with a potential future recommendation for health professionals or patients to universally disclose particular cancer predisposition genetic diagnosis to genetic family members. While much of the discussion remains applicable to all genetic diagnosis, the article focuses on the practice of disclosure within the context of BRCA1/2 diagnosis. An 'ethic of care' interpretation of legal tradition and current practice will serve to reconcile law and medical policy on the issue of physician disclosure of genetic results to family members without patient consent. © 2015 John Wiley & Sons Ltd.

  9. Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

    Science.gov (United States)

    Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

    2012-12-01

    Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

  10. Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations

    Directory of Open Access Journals (Sweden)

    Jun Kanazawa

    2017-10-01

    Conclusions: Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.

  11. The relationships between chemical and genetic differentiation and environmental factors across the distribution of Erigeron breviscapus (Asteraceae).

    Science.gov (United States)

    Li, Xiang; Peng, Li-yan; Zhang, Shu-dong; Zhao, Qin-shi; Yi, Ting-shuang

    2013-01-01

    Erigeron breviscapus (Vant.) Hand.-Mazz. is an important, widely used Chinese herb with scutellarin, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and erigoster B being its major active compounds. We aimed to resolve the influence of biotic and abiotic factors on the concentrations of these compounds and to determine appropriate cultivation methods to improve the yields of the four compounds in this herb. In order to detect the major genetic and natural environmental factors affecting the yields of these four compounds, we applied AFLP markers to investigate the population genetic differentiation and HPLC to measure the concentrations of four major active compounds among 23 wild populations which were located across almost the entire distribution of this species in China. The meteorological data including annual average temperature, annual average precipitation and annual average hours of sunshine were collected. The relationships among the concentrations of four compounds and environmental factors and genetic differentiation were studied. Low intraspecific genetic differentiation is detected, and there is no obvious correlation between the genetic differentiation and the contents of the chemical compounds. We investigated the correlation between the concentrationsof four compounds (scutellarin, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and erigoster B) and environmental factors. Concentrations of two compounds (1,5-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid) were correlated with environmental factors. The concentration of 1,5-dicaffeoylquinic acid is positively correlated with latitude, and is negatively correlated with the annual average temperature. The concentration of 3,5-dicaffeoylquinic acid is positively correlated with annual average precipitation. Therefore, changing cultivation conditions may significantly improve the yields of these two compounds. We found the concentration of scutellarin positively correlated with that of

  12. Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood.

    Science.gov (United States)

    Kendler, Kenneth S; Schmitt, Eric; Aggen, Steven H; Prescott, Carol A

    2008-06-01

    While both environmental and genetic factors are important in the etiology of psychoactive substance use (PSU), we know little of how these influences differ through development. To clarify the changing role of genes and environment in PSU from early adolescence through middle adulthood. Retrospective assessment by life history calendar, with univariate and bivariate structural modeling. General community. A total of 1796 members of male-male pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Levels of use of alcohol, caffeine, cannabis, and nicotine recorded for every year of the respondent's life. For nicotine, alcohol, and cannabis, familial environmental factors were critical in influencing use in early adolescence and gradually declined in importance through young adulthood. Genetic factors, by contrast, had little or no influence on PSU in early adolescence and gradually increased in their effect with increasing age. The sources of individual differences in caffeine use changed much more modestly over time. Substantial correlations were seen among levels of cannabis, nicotine, and alcohol use and specifically between caffeine and nicotine. In adolescence, those correlations were strongly influenced by shared effects from the familial environment. However, as individuals aged, more and more of the correlation in PSU resulted from genetic factors that influenced use of both substances. These results support an etiologic model for individual differences in PSU in which initiation and early patterns of use are strongly influenced by social and familial environmental factors while later levels of use are strongly influenced by genetic factors. The substantial correlations seen in levels of PSU across substances are largely the result of social environmental factors in adolescence, with genetic factors becoming progressively more important through early and middle adulthood.

  13. The Equal Opportunity Disorder: Autism Is on the Rise, and It Can Affect Any Family. Here's What You Need to Know

    Science.gov (United States)

    Whelan, Debra Lau

    2009-01-01

    The medical community understands surprisingly little about autism, referred to as autism spectrum disorders (ASD), because its symptoms can range from severe to a high-functioning autism, known as Asperger's syndrome. There's general agreement that a genetic predisposition coupled with unknown environmental triggers may explain what's behind it,…

  14. [Psychological distress in applicants for genetic screening for colorectal cancer].

    Science.gov (United States)

    Fantini, C; Pedinielli, J-L; Manouvrier, S

    2007-01-01

    Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified. Our purpose in this study was to determine whether subjects at risk who test for inherited colorectal cancer, are likely to develop a higher level of psychological distress than the norm, taking into consideration the particular history of this familial disease. The demographic and psychosocial aspects of our population was described using: 1) the State Trait Anxiety Inventory (STAI), 2) the Center for Epidemiologic Studies Depression (CES-D), 3) a perceived risk for the gene carrier, 4) subjective perception of personal vulnerability and 5) the role of the medical status (affected or not), which places the subject in either predisposition or predictive testing. Results show that our population had a higher predisposition for depressive disorders (chi2=9,3. p=0.002) and a significantly higher state of anxiety (chi2=9,3. p=0.002), prior to genetic counselling, compared with other populations. We found no evidence in the medical status, nor the perceived risk. However, the assessment of one's own personal vulnerability is related to psychological distress. These results highlight the particular vulnerability of subjects undergoing genetic testing as well as showing the pertinence of proposing psychological help throughout the process of these new specific diagnoses.

  15. Unraveling the genetic architecture of environmental variance of somatic cell score using high-density single nucleotide polymorphism and cow data from experimental farms.

    Science.gov (United States)

    Mulder, H A; Crump, R E; Calus, M P L; Veerkamp, R F

    2013-01-01

    In recent years, it has been shown that not only is the phenotype under genetic control, but also the environmental variance. Very little, however, is known about the genetic architecture of environmental variance. The main objective of this study was to unravel the genetic architecture of the mean and environmental variance of somatic cell score (SCS) by identifying genome-wide associations for mean and environmental variance of SCS in dairy cows and by quantifying the accuracy of genome-wide breeding values. Somatic cell score was used because previous research has shown that the environmental variance of SCS is partly under genetic control and reduction of the variance of SCS by selection is desirable. In this study, we used 37,590 single nucleotide polymorphism (SNP) genotypes and 46,353 test-day records of 1,642 cows at experimental research farms in 4 countries in Europe. We used a genomic relationship matrix in a double hierarchical generalized linear model to estimate genome-wide breeding values and genetic parameters. The estimated mean and environmental variance per cow was used in a Bayesian multi-locus model to identify SNP associated with either the mean or the environmental variance of SCS. Based on the obtained accuracy of genome-wide breeding values, 985 and 541 independent chromosome segments affecting the mean and environmental variance of SCS, respectively, were identified. Using a genomic relationship matrix increased the accuracy of breeding values relative to using a pedigree relationship matrix. In total, 43 SNP were significantly associated with either the mean (22) or the environmental variance of SCS (21). The SNP with the highest Bayes factor was on chromosome 9 (Hapmap31053-BTA-111664) explaining approximately 3% of the genetic variance of the environmental variance of SCS. Other significant SNP explained less than 1% of the genetic variance. It can be concluded that fewer genomic regions affect the environmental variance of SCS than the

  16. Genetic and Environmental Control of Neurodevelopmental Robustness in Drosophila.

    Directory of Open Access Journals (Sweden)

    David J Mellert

    Full Text Available Interindividual differences in neuronal wiring may contribute to behavioral individuality and affect susceptibility to neurological disorders. To investigate the causes and potential consequences of wiring variation in Drosophila melanogaster, we focused on a hemilineage of ventral nerve cord interneurons that exhibits morphological variability. We find that late-born subclasses of the 12A hemilineage are highly sensitive to genetic and environmental variation. Neurons in the second thoracic segment are particularly variable with regard to two developmental decisions, whereas its segmental homologs are more robust. This variability "hotspot" depends on Ultrabithorax expression in the 12A neurons, indicating variability is cell-intrinsic and under genetic control. 12A development is more variable and sensitive to temperature in long-established laboratory strains than in strains recently derived from the wild. Strains with a high frequency of one of the 12A variants also showed a high frequency of animals with delayed spontaneous flight initiation, whereas other wing-related behaviors did not show such a correlation and were thus not overtly affected by 12A variation. These results show that neurodevelopmental robustness is variable and under genetic control in Drosophila and suggest that the fly may serve as a model for identifying conserved gene pathways that stabilize wiring in stressful developmental environments. Moreover, some neuronal lineages are variation hotspots and thus may be more amenable to evolutionary change.

  17. Predisposition Factors of Career and Technical Education Transfer Students: A Hermeneutic Phenomenology Study

    Science.gov (United States)

    Hioki, Warren; Lester, Derek; Martinez, Mario

    2015-01-01

    Six college students, who were career and technical education (CTE) transfer students in the state of Nevada, were interviewed Spring Semester of 2009. The study used a hermeneutic phenomenology framework as the method to identify those predisposition variables that heavily influenced the students in their decision to transfer to a senior…

  18. A framework for a European network for a systematic environmental impact assessment of genetically modified organisms (GMO).

    NARCIS (Netherlands)

    Graef, F.; Römbke, J.; Binimelis, R.; Myhr, A.I.; Hilbeck, A.; Breckling, B.; Dalgaard, T.; Stachow, U.; Catacora-Vargas, G.; Bohn, T.; Quist, D.; Darvas, B.; Dudel, G.; Oehen, B.; Meyer, H.; Henle, K.; Wynne, B.; Metzger, M.J.; Knäbe, S.; Settele, J.; Székács, A.; Wurbs, A.; Bernard, J.P.; Murphy-Bokern, D.; Buiatti, M.; Giovannetti, M.; Debeljak, M.; Andersen, E.; Paetz, A.; Dzeroski, S.; Tappeser, B.; van Gestel, C.A.M.; Wosniok, W.; Séralini, G.-E.; Aslaksen, I.; Pesch, R.; Maly, S.; Werner, A.

    2012-01-01

    The assessment of the impacts of growing genetically modified (GM) crops remains a major political and scientific challenge in Europe. Concerns have been raised by the evidence of adverse and unexpected environmental effects and differing opinions on the outcomes of environmental risk assessments

  19. Genetic and environmental influences on adolescents' smoking involvement: a multi-informant twin study.

    Science.gov (United States)

    Seglem, Karoline Brobakke; Waaktaar, Trine; Ask, Helga; Torgersen, Svenn

    2015-03-01

    Studying monozygotic and dizygotic adolescent twin pairs of both sexes reared together, the present study examined the extent to which the variance in smoking involvement is attributable to genetic and environmental effects, and to what extent there are sex differences in the etiology. Questionnaire data on how often the adolescent had ever smoked tobacco was collected from a population-based twin sample consisting of seven national birth cohorts (ages 12-18), their mothers, and their fathers (N = 1,394 families). The data was analyzed with multivariate genetic modeling, using a multi-informant design. The etiological structure of smoking involvement was best represented in an ACE common pathway model, with smoking defined as a latent factor loading onto all three informants' reports. Estimates could be set equal across sexes. Results showed that adolescent lifetime smoking involvement was moderately heritable (37 %). The largest influence was from the shared environment (56 %), while environmental effects unique to each twin had minimal influence (7 %).

  20. Three-and-a-half-factor model? The genetic and environmental structure of the CBCL/6-18 internalizing grouping

    NARCIS (Netherlands)

    Franić, S.; Dolan, C.V.; Borsboom, D.; van Beijsterveldt, C.E.M.; Boomsma, D.I.

    2014-01-01

    In the present article, multivariate genetic item analyses were employed to address questions regarding the ontology and the genetic and environmental etiology of the Anxious/Depressed, Withdrawn, and Somatic Complaints syndrome dimensions of the Internalizing grouping of the Child Behavior

  1. Pre-disposition and epigenetics govern variation in bacterial survival upon stress.

    Directory of Open Access Journals (Sweden)

    Ming Ni

    Full Text Available Bacteria suffer various stresses in their unpredictable environment. In response, clonal populations may exhibit cell-to-cell variation, hypothetically to maximize their survival. The origins, propagation, and consequences of this variability remain poorly understood. Variability persists through cell division events, yet detailed lineage information for individual stress-response phenotypes is scarce. This work combines time-lapse microscopy and microfluidics to uniformly manipulate the environmental changes experienced by clonal bacteria. We quantify the growth rates and RpoH-driven heat-shock responses of individual Escherichia coli within their lineage context, stressed by low streptomycin concentrations. We observe an increased variation in phenotypes, as different as survival from death, that can be traced to asymmetric division events occurring prior to stress induction. Epigenetic inheritance contributes to the propagation of the observed phenotypic variation, resulting in three-fold increase of the RpoH-driven expression autocorrelation time following stress induction. We propose that the increased permeability of streptomycin-stressed cells serves as a positive feedback loop underlying this epigenetic effect. Our results suggest that stochasticity, pre-disposition, and epigenetic effects are at the source of stress-induced variability. Unlike in a bet-hedging strategy, we observe that cells with a higher investment in maintenance, measured as the basal RpoH transcriptional activity prior to antibiotic treatment, are more likely to give rise to stressed, frail progeny.

  2. Evidence for genetic association between chromosome 1q loci and predisposition to colorectal neoplasia.

    Czech Academy of Sciences Publication Activity Database

    Schubert, S.A.; Ruano, D.; Elsayed, F.A.; Boot, A.; Crobach, S.; Sarasqueta, A.F.; Wolffenbuttel, B.; van der Klauw, M.M.; Oosting, J.; Tops, C.M.; van Eijk, R.; Vasen, H.F.; Vossen, R.H.; Nielsen, M.; Castellví-Bel, S.; Ruiz-Ponte, C.; Tomlinson, I.; Dunlop, M.G.; Vodička, Pavel; Wijnen, J.T.; Hes, F.J.; Morreau, H.; de Miranda, N.F.; Sijmons, R.H.; van Wezel, T.

    2017-01-01

    Roč. 117, č. 8 (2017), s. 1215-1223 ISSN 0007-0920 R&D Projects: GA MŠk(CZ) LD14050 Institutional support: RVO:68378041 Keywords : hereditary colorectal cancer * colorectal polyps * homozygosity mapping Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.176, year: 2016

  3. The genetic and environmental foundations of political, psychological, social, and economic behaviors: a panel study of twins and families.

    Science.gov (United States)

    Hatemi, Peter K; Smith, Kevin; Alford, John R; Martin, Nicholas G; Hibbing, John R

    2015-06-01

    Here we introduce the Genetic and Environmental Foundations of Political and Economic Behaviors: A Panel Study of Twins and Families (PIs Alford, Hatemi, Hibbing, Martin, and Smith). This study was designed to explore the genetic and environmental influences on social, economic, and political behaviors and attitudes. It involves identifying the psychological mechanisms that operate on these traits, the heritability of complex economic and political traits under varying conditions, and specific genetic correlates of attitudes and behaviors. In addition to describing the study, we conduct novel analyses on the data, estimating the heritability of two traits so far unexplored in the extant literature: Machiavellianism and Baron-Cohen's Empathizing Quotient.

  4. Genetic and environmental influences on dimensional representations of DSM-IV cluster C personality disorders: a population-based multivariate twin study.

    Science.gov (United States)

    Reichborn-Kjennerud, Ted; Czajkowski, Nikolai; Neale, Michael C; Ørstavik, Ragnhild E; Torgersen, Svenn; Tambs, Kristian; Røysamb, Espen; Harris, Jennifer R; Kendler, Kenneth S

    2007-05-01

    The DSM-IV cluster C Axis II disorders include avoidant (AVPD), dependent (DEPD) and obsessive-compulsive (OCPD) personality disorders. We aimed to estimate the genetic and environmental influences on dimensional representations of these disorders and examine the validity of the cluster C construct by determining to what extent common familial factors influence the individual PDs. PDs were assessed using the Structured Interview for DSM-IV Personality (SIDP-IV) in a sample of 1386 young adult twin pairs from the Norwegian Institute of Public Health Twin Panel (NIPHTP). A single-factor independent pathway multivariate model was applied to the number of endorsed criteria for the three cluster C disorders, using the statistical modeling program Mx. The best-fitting model included genetic and unique environmental factors only, and equated parameters for males and females. Heritability ranged from 27% to 35%. The proportion of genetic variance explained by a common factor was 83, 48 and 15% respectively for AVPD, DEPD and OCPD. Common genetic and environmental factors accounted for 54% and 64% respectively of the variance in AVPD and DEPD but only 11% of the variance in OCPD. Cluster C PDs are moderately heritable. No evidence was found for shared environmental or sex effects. Common genetic and individual environmental factors account for a substantial proportion of the variance in AVPD and DEPD. However, OCPD appears to be largely etiologically distinct from the other two PDs. The results do not support the validity of the DSM-IV cluster C construct in its present form.

  5. Toxic hydrogen sulfide and dark caves: phenotypic and genetic divergence across two abiotic environmental gradients in Poecilia mexicana.

    Science.gov (United States)

    Tobler, Michael; Dewitt, Thomas J; Schlupp, Ingo; García de León, Francisco J; Herrmann, Roger; Feulner, Philine G D; Tiedemann, Ralph; Plath, Martin

    2008-10-01

    Divergent natural selection drives evolutionary diversification. It creates phenotypic diversity by favoring developmental plasticity within populations or genetic differentiation and local adaptation among populations. We investigated phenotypic and genetic divergence in the livebearing fish Poecilia mexicana along two abiotic environmental gradients. These fish typically inhabit nonsulfidic surface rivers, but also colonized sulfidic and cave habitats. We assessed phenotypic variation among a factorial combination of habitat types using geometric and traditional morphometrics, and genetic divergence using quantitative and molecular genetic analyses. Fish in caves (sulfidic or not) exhibited reduced eyes and slender bodies. Fish from sulfidic habitats (surface or cave) exhibited larger heads and longer gill filaments. Common-garden rearing suggested that these morphological differences are partly heritable. Population genetic analyses using microsatellites as well as cytochrome b gene sequences indicate high population differentiation over small spatial scale and very low rates of gene flow, especially among different habitat types. This suggests that divergent environmental conditions constitute barriers to gene flow. Strong molecular divergence over short distances as well as phenotypic and quantitative genetic divergence across habitats in directions classic to fish ecomorphology suggest that divergent selection is structuring phenotypic variation in this system.

  6. Advances in genetic detection of kidney disease

    International Nuclear Information System (INIS)

    Dosekun, Akinsan K.; Foringer, John R.; Kone, Bruce C.

    2003-01-01

    The Human Genome Project has provided a vast amount of molecular genetic information for the analysis of normal and diseased genes. This new information provides new opportunities for precise diagnosis, assessment of predisposition and risk factors and novel therapeutic strategies. At the same time, this constantly expanding knowledge base represents on e of the most difficult challenges in molecular medicine. For monogenic disease nearly 2000 human disease genes have thus for been identified. Most of these conditions are characterized by large mutational variation and even greater phenotypic variation. In nephrology, several genetic diseases have been elucidated that provide new insight into the structure, function and developmental biology of the glomerulus, tubules and urogenital tracts, as well as renal cell tumors. Great improvements in the diagnostic resolution of genetic diseases have been achieved, such that single base pair mutations can be readily detected. Because of accurate diagnosis and risk assessment, genetic testing may be valuable in improving disease management and preventive care when genotype-specific therapies are available. Moreover, such testing may identify de novo mutations and potentially aid in understanding the disease process. This review summarizes recent advances in the renal genetic database and methods for genetic testing of renal diseases. (author)

  7. Behavioral and environmental modification of the genetic influence on body mass index: A twin study

    Science.gov (United States)

    Horn, Erin E.; Turkheimer, Eric; Strachan, Eric; Duncan, Glen E.

    2015-01-01

    Body mass index (BMI) has a strong genetic basis, with a heritability around 0.75, but is also influenced by numerous behavioral and environmental factors. Aspects of the built environment (e.g., environmental walkability) are hypothesized to influence obesity by directly affecting BMI, by facilitating or inhibiting behaviors such as physical activity that are related to BMI, or by suppressing genetic tendencies toward higher BMI. The present study investigated relative influences of physical activity and walkability on variance in BMI using 5,079 same-sex adult twin pairs (70% monozygotic, 65% female). High activity and walkability levels independently suppressed genetic variance in BMI. Estimating their effects simultaneously, however, suggested that the walkability effect was mediated by activity. The suppressive effect of activity on variance in BMI was present even with a tendency for low-BMI individuals to select into environments that require higher activity levels. Overall, our results point to community- or macro-level interventions that facilitate individual-level behaviors as a plausible approach to addressing the obesity epidemic among U.S. adults. PMID:25894925

  8. Differential methylation between ethnic sub-groups reflects the effect of genetic ancestry and environmental exposures

    Science.gov (United States)

    Galanter, Joshua M; Gignoux, Christopher R; Oh, Sam S; Torgerson, Dara; Pino-Yanes, Maria; Thakur, Neeta; Eng, Celeste; Hu, Donglei; Huntsman, Scott; Farber, Harold J; Avila, Pedro C; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Meade, Kelly; Serebrisky, Denise; Rodríguez-Cintrón, William; Kumar, Rajesh; Rodríguez-Santana, Jose R; Seibold, Max A; Borrell, Luisa N; Burchard, Esteban G; Zaitlen, Noah

    2017-01-01

    Populations are often divided categorically into distinct racial/ethnic groups based on social rather than biological constructs. Genetic ancestry has been suggested as an alternative to this categorization. Herein, we typed over 450,000 CpG sites in whole blood of 573 individuals of diverse Hispanic origin who also had high-density genotype data. We found that both self-identified ethnicity and genetically determined ancestry were each significantly associated with methylation levels at 916 and 194 CpGs, respectively, and that shared genomic ancestry accounted for a median of 75.7% (IQR 45.8% to 92%) of the variance in methylation associated with ethnicity. There was a significant enrichment (p=4.2×10-64) of ethnicity-associated sites amongst loci previously associated environmental exposures, particularly maternal smoking during pregnancy. We conclude that differential methylation between ethnic groups is partially explained by the shared genetic ancestry but that environmental factors not captured by ancestry significantly contribute to variation in methylation. DOI: http://dx.doi.org/10.7554/eLife.20532.001 PMID:28044981

  9. Genetic and Environmental Links between Natural Language Use and Cognitive Ability in Toddlers

    Science.gov (United States)

    Canfield, Caitlin F.; Edelson, Lisa R.; Saudino, Kimberly J.

    2017-01-01

    Although the phenotypic correlation between language and nonverbal cognitive ability is well-documented, studies examining the etiology of the covariance between these abilities are scant, particularly in very young children. The goal of this study was to address this gap in the literature by examining the genetic and environmental links between…

  10. Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children.

    Science.gov (United States)

    Mrena, S; Savola, K; Kulmala, P; Reijonen, H; Ilonen, J; Akerblom, H K; Knip, M

    2003-06-01

    We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P siblings of affected children.

  11. Relationship between genetic and environmental factors and hypercholesterolemia in children.

    Science.gov (United States)

    Robledo, Jorge A; Siccardi, Leonardo J

    2016-10-01

    Pediatric hypercholesterolemia has increased over the past decades. Knowing the environmental and genetic factors that have an impact on it would allow establishing more adequate screening guidelines. To determine if there is an association between genetic and environmental factors and hypercholesterolemia in children. To assess the predictive qualities of outcome measures associated with hypercholesterolemia. Observational, analytical, cross-sectional study. students from all schools located in Jovita. Age: > 6 and hypercholesterolemia. Three hundred and eighty-two students were included. Their mean cholesterol level was 168 mg/dL, and 13.4% had hypercholesterolemia. A sedentary lifestyle was observed in 22.8%, and obesity, in 10.5%. A positive FMH, a high/ middle SEL, and obesity were associated with hypercholesterolemia (OR: 2.10, 2.10 and 2.05, respectively). No association was found between physical activity and fat/cholesterol intake and hypercholesterolemia. A positive FMH and a high/middle SEL were sensitive enough (75% and 88%) to predict hypercholesterolemia. The presence of hypercholesterolemia inboth parents in relation to hypercholesterolemia in their child showed an OR of 9.59, a sensitivity of 73%, a specificity of 71%, a positive predictive value of 57%, and a negative predictive value of 83%. A positive FMH, a high/ middle SEL, and obesity were associated with hypercholesterolemia in children. The presence of hypercholesterolemia in both parents was associated with hypercholesterolemia in their child and showed itself to be a great potential predictor and screening criterion. Sociedad Argentina de Pediatría.

  12. Genetic and environmental features for oil composition in olive varieties

    Directory of Open Access Journals (Sweden)

    Bervillé André Jean

    2014-09-01

    Full Text Available Consumption of olive oil helps both prevent and cure heart disease. Olive oils vary in their fatty acid profiles as well as those of other secondary metabolites (phenols, sterols, and terpene compounds. We seek to distinguish the genetic bases from the environmental factors that cause these variations. The genetic base is indeed wide: varieties originate in different domestication occurrences, from different oleaster trees and in differing climatic regimes. With the aid of diagrams, we set out briefly the oil synthesis pathway for fruits in comparison with that of seeds, and the specific aspects of olive oil in particular. Varieties of olive have appeared that are adapted to regions with harsh conditions where the oleaster could not thrive. Environmental stresses have consequences on drupes and their oil profiles; these have been highlighted in European countries through the use of appellations. Whilst stresses tend to enhance the quality of the end product, they do however decrease final yields with potential negative impacts on olive growers’ incomes. Irrigation experiments are underway in order to determine the optimal amount of watering. In breeding new varieties, the result sought is that of accumulating pest tolerances and fruit-quality characteristics; selection programmes are however expensive as they necessitate observations over many years. Consumers have choice across a range of appellations with different organoleptic specificities at different prices, and whatever the appellation of the oil they can expect a positive effect on their health.

  13. Genetic predisposition to testicular cancer

    NARCIS (Netherlands)

    Lutke Holzik, Martijn Frederik

    2007-01-01

    Alhoewel zaadbalkanker een zeldzame ziekte is, is het toch de meest voorkomende vorm van kanker bij mannen tussen de 15 en 40 jaar. De ziekte is tegenwoordig goed te behandelen en de 10 jaars overleving is ongeveer 90%. Het hebben van een familielid met zaadbalkanker is de sterkste risicofactor voor

  14. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people.

    NARCIS (Netherlands)

    Henquet, C.J.; Krabbendam, L.; Spauwen, P.H.M.; Kaplan, C.; Lieb, R.; Wittchen, H.U.; Os, J. van

    2005-01-01

    OBJECTIVE: To investigate the relation between cannabis use and psychotic symptoms in individuals with above average predisposition for psychosis who first used cannabis during adolescence. DESIGN: Analysis of prospective data from a population based sample. Assessment of substance use,

  15. [Genetic and environmental contributions to body mass index in a Spanish adolescent twin sample].

    Science.gov (United States)

    Iranzo-Tatay, Carmen; Gimeno-Clemente, Natalia; Livianos-Aldana, Lorenzo; Rojo-Moreno, Luis

    2015-08-21

    Twin and family studies support large genetic influences on variability in body mass index (BMI), with heritability estimates ranging from 47% to over 90%. Our objective was to study the relative contributions of genetics and environment to BMI, evaluating sex differences, in an adolescent twin sample from Valencia, Spain. Five hundred eighty-four pairs of adolescent twins between 13 and 18 years of age completed the study (82 monozygotic [MZ] and 87 dizygotic [DZ] pairs of male twins, 118 MZ and 102 DZ pairs of female twins, and 195 opposite-sex pairs of DZ twins). To determine zygosity, teachers responded a questionnaire on physical similarity. They also measured the participant's height and weight. BMI was calculated and weight status was determined according to age. We used twin models to assess genetic and environmental (common and unique) factors affecting BMI. There was a 7.1% frequency of overweight and 2.8% of obesity. The estimated heritability of BMI was 88.0% in boys and 72.1% in girls, with the remaining variance attributable to non-shared environment in boys (12.0%) and 8.8% in girls. It was only in girls that common environment had an effect on BMI. Genetics appears to play an important role in explaining the variability in BMI in the adolescence, with slight variations between boys and girls. Common environmental factors exert their influence on BMI only in girls. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. Genetic and environmental transactions underlying the association between physical fitness/physical exercise and body composition

    DEFF Research Database (Denmark)

    Johnson, Wendy; de Ruiter, Ingrid; Kyvik, Kirsten Ohm

    2015-01-01

    suppressed variance in adiposity, but this study provided further insight. Variance suppression appeared to have both genetic and environmental pathways. Some mean effects appeared due to reciprocal influences of environmental circumstances differing among families but not between co-twins, suggesting...... in attempting to understand the pathways involved in their linkages, and constraint in interpreting results if only single measures are available. Future research indications include identifying which physical activity-related environmental circumstances have relatively uniform effects on adiposity in everyone......, and which should be individually tailored to maximize motivation to continue involvement....

  17. Genetic and Environmental Influences on Smoking Behavior across Adolescence and Young Adulthood in the Virginia Twin Study of Adolescent Behavioral Development and the Transitions to Substance Abuse Follow-Up.

    Science.gov (United States)

    Do, Elizabeth K; Prom-Wormley, Elizabeth C; Eaves, Lindon J; Silberg, Judy L; Miles, Donna R; Maes, Hermine H

    2015-02-01

    Little is known regarding the underlying relationship between smoking initiation and current quantity smoked during adolescence into young adulthood. It is possible that the influences of genetic and environmental factors on this relationship vary across sex and age. To investigate this further, the current study applied a common causal contingency model to data from a Virginia-based twin study to determine: (1) if the same genetic and environmental factors are contributing to smoking initiation and current quantity smoked; (2) whether the magnitude of genetic and environmental factor contributions are the same across adolescence and young adulthood; and (3) if qualitative and quantitative differences in the sources of variance between males and females exist. Study results found no qualitative or quantitative sex differences in the relationship between smoking initiation and current quantity smoked, though relative contributions of genetic and environmental factors changed across adolescence and young adulthood. More specifically, smoking initiation and current quantity smoked remain separate constructs until young adulthood, when liabilities are correlated. Smoking initiation is explained by genetic, shared, and unique environmental factors in early adolescence and by genetic and unique environmental factors in young adulthood; while current quantity smoked is explained by shared environmental and unique environmental factors until young adulthood, when genetic and unique environmental factors play a larger role.

  18. Genetic and environmental effects on a meat spotting defect in seasoned dry-cured ham

    Directory of Open Access Journals (Sweden)

    Giulio Pagnacco

    2011-01-01

    Full Text Available Purpose of this investigation was to determine the nature of a visible spotting defect on the slice of dry-cured ham and assess environmental and genetic causes of this frequent problem. A group of 233 pigs from commercial cross-breeding lines, progeny of ten boars and forty seven sows, was raised in a single herd to obtain the “Italian Heavy Pig”, typically slaughtered at 160 ± 10 kg live weight and older than 9 months of age. A quality evaluation of their right dry-cured hams, seasoned according to the Parma P.D.O. protocol, was undertaken. Each ham was cross-sectioned to obtain a slice of Semimembranosus, Semitendinosus and Biceps Femoris muscles. The focused phenotype was the presence/absence of brownish spots in these muscles, which represent a remarkable meat defect with strong impact on the final sale price. Environmental and management factors were considered in order to evaluate variability related to the phenotype. Animals were raised on two different flooring types (concrete and slatted floor and a Vitamin C diet was also supplemented in the last 45 days before slaughtering to half of the animals. While the pre-planned environmental effects did not show any significant contribution to the total variability of the phenotype, the genetic analysis showed a near to zero value for heritability with a consistent 0.32 repeatability. The proportion of the total phenotypic variance was explained by an important dominance genetic component (0.26 indicating that the technological seasoning process may play a secondary role on the expression of this phenotype.

  19. Metabolic syndrome-related composite factors over 5 years in the STANISLAS family study: genetic heritability and common environmental influences.

    Science.gov (United States)

    Herbeth, Bernard; Samara, Anastasia; Ndiaye, Coumba; Marteau, Jean-Brice; Berrahmoune, Hind; Siest, Gérard; Visvikis-Siest, Sophie

    2010-06-03

    We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France. At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis. At entrance, genetic heritability was high (20 to 44%) for plasma lipids and lipoproteins, uric acid, fasting glucose, and the related clusters "risk lipids" and "protective lipids". Intermediate or low genetic heritability (less than 20%) was shown for triglycerides, adiposity indices, blood pressure, hepatic enzyme activity, inflammatory makers and the related clusters: "liver enzymes", "adiposity/blood pressure" and "inflammation". Moreover, common environmental influences were significant for all the parameters. With regard to 5-year changes, polygenic variance was low and not statistically significant for any of the individual variables or clusters whereas shared environment influence was significant. In these young families, genetic heritability of metabolic syndrome-related traits was generally lower than previously reported while the common environmental influences were greater. In addition, only shared environment contributed to short-term changes of these traits. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Integrating mechanistic and polymorphism data to characterize human genetic susceptibility for environmental chemical risk assessment in the 21st century

    International Nuclear Information System (INIS)

    Mortensen, Holly M.; Euling, Susan Y.

    2013-01-01

    Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment

  1. Three-and-a-Half-Factor Model? The Genetic and Environmental Structure of the CBCL/6–18 Internalizing Grouping

    NARCIS (Netherlands)

    Franic, S.F.; Dolan, C.V.; Borsboom, D.; van Beijsterveldt, C.E.M.; Boomsma, D.I.

    2014-01-01

    In the present article, multivariate genetic item analyses were employed to address questions regarding the ontology and the genetic and environmental etiology of the Anxious/Depressed, Withdrawn, and Somatic Complaints syndrome dimensions of the Internalizing grouping of the Child Behavior

  2. Environmental and genetic factors influence the vitamin D content of cows' milk.

    Science.gov (United States)

    Weir, R R; Strain, J J; Johnston, M; Lowis, C; Fearon, A M; Stewart, S; Pourshahidi, L K

    2017-02-01

    Vitamin D is obtained by cattle from the diet and from skin production via UVB exposure from sunlight. The vitamin D status of the cow impacts the vitamin D content of the milk produced, much like human breast milk, with seasonal variation in the vitamin D content of milk well documented. Factors such as changes in husbandry practices therefore have the potential to impact the vitamin D content of milk. For example, a shift to year-round housing from traditional practices of cattle being out to graze during the summer months and housed during the winter only, minimises exposure to the sun and has been shown to negatively influence the vitamin D content of the milk produced. Other practices such as changing dietary sources of vitamin D may also influence the vitamin D content of milk, and evidence exists to suggest genetic factors such as breed can cause variation in the concentrations of vitamin D in the milk produced. The present review aims to provide an overview of the current understanding of how genetic and environmental factors influence the vitamin D content of the milk produced by dairy cattle. A number of environmental and genetic factors have previously been identified as having influence on the nutritional content of the milk produced. The present review highlights a need for further research to fully elucidate how farmers could manipulate the factors identified to their advantage with respect to increasing the vitamin D content of milk and standardising it across the year.

  3. Genetic and environmental overlap between borderline personality disorder traits and psychopathy: evidence for promotive effects of factor 2 and protective effects of factor 1.

    Science.gov (United States)

    Hunt, E; Bornovalova, M A; Patrick, C J

    2015-05-01

    Previous studies have reported strong genetic and environmental overlap between antisocial-externalizing (factor 2; F2) features of psychopathy and borderline personality disorder (BPD) tendencies. However, this line of research has yet to examine etiological associations of affective-interpersonal (factor 1, F1) features of psychopathy with BPD tendencies. The current study investigated differential phenotypic and genetic overlap of psychopathy factors 1 and 2 with BPD tendencies in a sample of over 250 male and female community-recruited adult twin pairs. Consistent with previous research, biometric analyses revealed strong genetic and non-shared environmental correlations of F2 with BPD tendencies, suggesting that common genetic and non-shared environmental factors contribute to both phenotypes. In contrast, negative genetic and non-shared environmental correlations were observed between F1 and BPD tendencies, indicating that the genetic factors underlying F1 serve as protective factors against BPD. No gender differences emerged in the analyses. These findings provide further insight into associations of psychopathic features - F1 as well as F2 - and BPD tendencies. Implications for treatment and intervention are discussed, along with how psychopathic traits may differentially influence the manifestation of BPD tendencies.

  4. The relationships between chemical and genetic differentiation and environmental factors across the distribution of Erigeron breviscapus (Asteraceae.

    Directory of Open Access Journals (Sweden)

    Xiang Li

    Full Text Available AIMS: Erigeron breviscapus (Vant. Hand.-Mazz. is an important, widely used Chinese herb with scutellarin, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and erigoster B being its major active compounds. We aimed to resolve the influence of biotic and abiotic factors on the concentrations of these compounds and to determine appropriate cultivation methods to improve the yields of the four compounds in this herb. METHODS: In order to detect the major genetic and natural environmental factors affecting the yields of these four compounds, we applied AFLP markers to investigate the population genetic differentiation and HPLC to measure the concentrations of four major active compounds among 23 wild populations which were located across almost the entire distribution of this species in China. The meteorological data including annual average temperature, annual average precipitation and annual average hours of sunshine were collected. The relationships among the concentrations of four compounds and environmental factors and genetic differentiation were studied. IMPORTANT FINDINGS: Low intraspecific genetic differentiation is detected, and there is no obvious correlation between the genetic differentiation and the contents of the chemical compounds. We investigated the correlation between the concentrationsof four compounds (scutellarin, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and erigoster B and environmental factors. Concentrations of two compounds (1,5-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid were correlated with environmental factors. The concentration of 1,5-dicaffeoylquinic acid is positively correlated with latitude, and is negatively correlated with the annual average temperature. The concentration of 3,5-dicaffeoylquinic acid is positively correlated with annual average precipitation. Therefore, changing cultivation conditions may significantly improve the yields of these two compounds. We found the concentration

  5. Informing family members about a hereditary predisposition to cancer: attitudes and practices among clinical geneticists

    NARCIS (Netherlands)

    Stol, Y.; Menko, F.H.; Westerman, M.J.; Janssens, M.J.P.A.

    2010-01-01

    If a hereditary predisposition to colorectal cancer or breast cancer is diagnosed, most guidelines state that clinical geneticists should request index patients to inform their at-risk relatives about the existence of this condition in their family, thus enabling them to consider presymptomatic

  6. Bridging Home and Host Country: Educational Predispositions of Chinese and Indian Recent Immigrant Families

    Science.gov (United States)

    Gordon, June A.; Liu, Xiangyan

    2015-01-01

    This research focuses on the predispositions that recent Chinese and Indian immigrant families bring with them to the United States and how these are reinforced by the communities in which they locate. The findings draw from 144 interviews in California. Three themes dominate: positioning through schooling, transnational family, and extended…

  7. Genetic and environmental dissections of sub-phenotypes of metabolic syndrome in the chinese population: a twin-based heritability study

    DEFF Research Database (Denmark)

    Duan, Haiping; Pang, Zengchang; Zhang, Dongfeng

    2011-01-01

    contains 654 twins collected in the Qingdao municipality. A total of 10 phenotypes covering anthropometric measurements, plasma glucose levels, lipids, blood pressures etc. were examined. Univariate and bivariate structural equation models were fitted for assessing the genetic and environmental...... contributions. Results: The AE model combining additive genetic (A) and unique environmental (E) factors produced the best fit for all phenotypes except for triglyceride. Modest to high heritability estimates were obtained in univariate analysis ranging from 0.5 for total cholesterol to 0.78 for weight...

  8. The Genetic Architecture of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Samuel T Jerram

    2017-08-01

    Full Text Available Type 1 diabetes (T1D is classically characterised by the clinical need for insulin, the presence of disease-associated serum autoantibodies, and an onset in childhood. The disease, as with other autoimmune diseases, is due to the interaction of genetic and non-genetic effects, which induce a destructive process damaging insulin-secreting cells. In this review, we focus on the nature of this interaction, and how our understanding of that gene–environment interaction has changed our understanding of the nature of the disease. We discuss the early onset of the disease, the development of distinct immunogenotypes, and the declining heritability with increasing age at diagnosis. Whilst Human Leukocyte Antigens (HLA have a major role in causing T1D, we note that some of these HLA genes have a protective role, especially in children, whilst other non-HLA genes are also important. In adult-onset T1D, the disease is often not insulin-dependent at diagnosis, and has a dissimilar immunogenotype with reduced genetic predisposition. Finally, we discuss the putative nature of the non-genetic factors and how they might interact with genetic susceptibility, including preliminary studies of the epigenome associated with T1D.

  9. Genetic and Environmental Contributions to Behavioral Stability and Change in Children 6-36 months of Age Using Louisville Twin Study Data.

    Science.gov (United States)

    Davis, Deborah Winders; Finkel, Deborah; Turkheimer, Eric; Dickens, William

    2015-11-01

    The Infant Behavior Record (IBR) from the Bayley Scales of Infant Development has been used to study behavioral development since the 1960s. Matheny (1983) examined behavioral development at 6, 12, 18, and 24 months from the Louisville Twin Study (LTS). The extracted temperament scales included Task Orientation, Affect-Extraversion, and Activity. He concluded that monozygotic twins were more similar than same-sex dizygotic twins on these dimensions. Since this seminal work was published, a larger LTS sample and more advanced analytical methods are available. In the current analyses, Choleksy decomposition was applied to behavioral data (n = 1231) from twins 6-36 months. Different patterns of genetic continuity vs genetic innovations were identified for each IBR scale. Single common genetic and shared environmental factors explained cross-age twin similarity in the Activity scale. Multiple shared environmental factors and a single genetic factor coming on line at age 18 months contributed to Affect-Extraversion. A single shared environmental factor and multiple genetic factors explained cross-age twin similarity in Task Orientation.

  10. Genetic and environmental correlates of morphological variation in a marine fish: the case of Baltic Sea herring ( Clupea harengus )

    DEFF Research Database (Denmark)

    Jørgensen, H.B.H.; Pertoldi, C.; Hansen, Michael Møller

    2008-01-01

    Baltic Sea herring (Clupea harengus) have been shown to exhibit morphological differences across the marked salinity and temperature gradients in the region. Here we analyse genetic (nine microsatellite loci), morpho metric (skull shape), and meristic (pectoral fin rays and number of vertebrae...... and plastic responses. Skull shape, including and excluding size variation, differed significantly among samples, both temporally and spatially. Genetic and morphometric distances were correlated, especially when size variation was excluded from the analysis. When size variation was included, skull shape...... variation was more closely correlated with environmental distances among spawning locations. Vertebrate number differed among samples and was correlated with environmental distances, whereas the number of fin rays was not. Genetic and geographic distances among samples were not correlated....

  11. Genetic and environmental variances of bone microarchitecture and bone remodeling markers: a twin study.

    Science.gov (United States)

    Bjørnerem, Åshild; Bui, Minh; Wang, Xiaofang; Ghasem-Zadeh, Ali; Hopper, John L; Zebaze, Roger; Seeman, Ego

    2015-03-01

    All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size - void volumes (porosity), which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) white female twin pairs aged 40 to 61 years. Images obtained using high-resolution peripheral quantitative computed tomography were analyzed using StrAx1.0, a nonthreshold-based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72% to 81% (standard errors ∼18%) for the distal tibial total, cortical, and medullary cross-sectional area (CSA); 67% and 61% for total cortical porosity, before and after adjusting for total CSA, respectively; 51% for trabecular volumetric bone mineral density (vBMD; all p accounted for 47% to 68% of the variance (all p ≤ 0.001). Cross-twin cross-trait correlations between tibial cortical porosity and medullary CSA were higher for MZ (rMZ  = 0.49) than DZ (rDZ  = 0.27) pairs before (p = 0.024), but not after (p = 0.258), adjusting for total CSA. For the remodeling markers, the data were consistent with genetic factors accounting for 55% to 62% of the variance. We infer that middle-aged women differ in their bone microarchitecture and remodeling markers more because of differences in their genetic factors than

  12. Genetic Damage Induced by Accidental Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Beatriz Pérez-Cadahía

    2006-01-01

    Full Text Available Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC, and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE, micronucleus (MN test, and comet assay. Four groups of individuals were included: volunteers (V, hired manual workers (MW, hired high-pressure cleaner workers (HPW and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.

  13. Surgical Management of Chronic Pancreatitis.

    Science.gov (United States)

    Parekh, Dilip; Natarajan, Sathima

    2015-10-01

    Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

  14. Robust symptom networks in recurrent major depression across different levels of genetic and environmental risk

    NARCIS (Netherlands)

    van Loo, H.M.; Van Borkulo, C.D.; Peterson, R.E.; Fried, E.I.; Aggen, S.H.; Borsboom, D.; Kendler, K.S.

    BACKGROUND: Genetic risk and environmental adversity-both important risk factors for major depression (MD)-are thought to differentially impact on depressive symptom types and associations. Does heterogeneity in these risk factors result in different depressive symptom networks in patients with MD?

  15. Quantify environmental effects in shaping the genetic diversification pattern of Oncomelania hupensis and its implications in surveillance of human susceptibility to Schistosomiasis

    Science.gov (United States)

    Liang, L.; Liao, J. S.; Gong, P.

    2012-12-01

    The transmission and distribution of schistomiasis, one of the most serious infectious diseases in East and Southeast Asia, tied closely to its unique intermediate snail host Oncomelania hupensis. The coevolved relationships of O. hupensis populations with its parasite Schistosoma japonisum are important in understanding the mechanism of disease spread. The genetic diversification pattern within population is supposed to influence the amount of parasite loads, and the susceptibility of snails determined the chance for human or mammals to get infected. Meanwhile, intervening environmental features had been long suggested to affect snail population dynamics and evolutionary trajectories of species. However, no comprehensive study referring to the above topics has been carried out on O.hupensis populations before. In this study, we reanalyzed published data in mainland China to evaluate whether human infection rate and genetic diversification patterns are related under natural environment. Besides that, we used an array of remotely sensed image derived environmental variables to quantify the amount of variation in population genetic structure that could be explained by those factors by landscape genetic analysis. We found that human schistosomiasis infection rate is positively correlated with intra-population genetic diversification and inter-population genetic exchange, which is contradictory with the Red Queen hypothesis. The patterns of genetic diversification are better revealed when non-Euclidean, environmentally determined distance measures or features are used in large heterogeneous landscape. The impact of stream connectivity on the snail inter-population genetic distances does not so evident unless taking wetlands into calculation, and thus control activities planned solely along river systems may be suboptimal. Climate features have a stronger impact on genetic structure of snails than topology, and precipitation seasonality dominates the highest proportion

  16. The Association of Genetic Predisposition to Depressive Symptoms with Non-suicidal and Suicidal Self-Injuries

    NARCIS (Netherlands)

    Maciejewski, Dominique F; Renteria, Miguel E; Abdellaoui, Abdel; Medland, Sarah E; Few, Lauren R; Gordon, Scott D; Madden, Pamela A F; Montgomery, Grant W; Trull, Timothy J; Heath, Andrew C; Statham, Dixie J; Martin, Nicholas G; Zietsch, Brendan P; Verweij, Karin J. H.

    Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of

  17. The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-injuries

    NARCIS (Netherlands)

    Maciejewski, D.F.; Renteria, M.E.; Abdellaoui, A.; Medland, S.E.; Few, L.R.; Gordon, S.D.; Madden, P.A.F.; Montgomery, G.W.; Trull, T.J.; Heath, A.C.; Statham, D.J.; Martin, N.G.; Zietsch, B.P.; Verweij, K.J.H.

    2017-01-01

    Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of

  18. Reflections on the Origins and Evolution of Genetic Toxicology and the Environmental Mutagen Society

    Energy Technology Data Exchange (ETDEWEB)

    Wassom, John S. [Oak Ridge National Laboratory (Retired); Malling, Heinrich V. [National Institute of Environmental Health Sciences (NIEHS); Sankaranarayanan, K. [Leiden University; Lu, Po-Yung [ORNL

    2010-01-01

    This article traces the development of the field of mutagenesis and its metamorphosis into the research area we now call genetic toxicology. In 1969 this transitional event led to the founding of the Environmental Mutagen Society (EMS). The charter of this new Society was to encourage interest in and study of mutagens in the human environment, particularly as these may be of concern to public health. As the mutagenesis field unfolded and expanded, the lexicon changed and new wording appeared to better describe this evolving area of research. The term genetic toxicology was coined and became an important subspecialty of the broad area of toxicology. Genetic toxicology is now set for a thorough reappraisal of its methods, goals, and priorities to meet the challenges of the 21st Century. To better understand these challenges, we have revisited the primary goal that the EMS founders had in mind for the Society s main mission and objective, namely, the quantitative assessment of genetic (hereditary) risks to human populations exposed to environmental agents. We also have reflected upon some of the seminal events over the last 40 years that have influenced the advancement of the genetic toxicology discipline and the extent to which the Society s major goal and allied objectives have been achieved. Additionally, we have provided suggestions on how EMS can further advance the science of genetic toxicology in the postgenome era. Chronicling all events and publications that influenced the development of the mutagenesis and genetic toxicology research area for this article was not possible, but some key happenings that contributed to the field s development have been reviewed. Events that led to the origin of EMS are also presented in celebration of the Society s 40th anniversary. Any historical accounting will have perceived deficiencies. Key people, publications, or events that some readers may feel have had significant impact on development of the subject under review may

  19. Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants.

    Directory of Open Access Journals (Sweden)

    Maria Sellitto

    Full Text Available Celiac disease (CD is a unique autoimmune disorder in which the genetic factors (DQ2/DQ8 and the environmental trigger (gluten are known and necessary but not sufficient for its development. Other environmental components contributing to CD are poorly understood. Studies suggest that aspects of gluten intake might influence the risk of CD occurrence and timing of its onset, i.e., the amount and quality of ingested gluten, together with the pattern of infant feeding and the age at which gluten is introduced in the diet. In this study, we hypothesize that the intestinal microbiota as a whole rather than specific infections dictates the switch from tolerance to immune response in genetically susceptible individuals. Using a sample of infants genetically at risk of CD, we characterized the longitudinal changes in the microbial communities that colonize infants from birth to 24 months and the impact of two patterns of gluten introduction (early vs. late on the gut microbiota and metabolome, and the switch from gluten tolerance to immune response, including onset of CD autoimmunity. We show that infants genetically susceptible to CD who are exposed to gluten early mount an immune response against gluten and develop CD autoimmunity more frequently than at-risk infants in which gluten exposure is delayed until 12 months of age. The data, while derived from a relatively small number of subjects, suggest differences between the developing microbiota of infants with genetic predisposition for CD and the microbiota from infants with a non-selected genetic background, with an overall lack of bacteria of the phylum Bacteriodetes along with a high abundance of Firmicutes and microbiota that do not resemble that of adults even at 2 years of age. Furthermore, metabolomics analysis reveals potential biomarkers for the prediction of CD. This study constitutes a definite proof-of-principle that these combined genomic and metabolomic approaches will be key to

  20. Genetic Basis of Positive and Negative Symptom Domains in Schizophrenia.

    Science.gov (United States)

    Xavier, Rose Mary; Vorderstrasse, Allison

    2017-10-01

    Schizophrenia is a highly heritable disorder, the genetic etiology of which has been well established. Yet despite significant advances in genetics research, the pathophysiological mechanisms of this disorder largely remain unknown. This gap has been attributed to the complexity of the polygenic disorder, which has a heterogeneous clinical profile. Examining the genetic basis of schizophrenia subphenotypes, such as those based on particular symptoms, is thus a useful strategy for decoding the underlying mechanisms. This review of literature examines the recent advances (from 2011) in genetic exploration of positive and negative symptoms in schizophrenia. We searched electronic databases PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature using key words schizophrenia, symptoms, positive symptoms, negative symptoms, cognition, genetics, genes, genetic predisposition, and genotype in various combinations. We identified 115 articles, which are included in the review. Evidence from these studies, most of which are genetic association studies, identifies shared and unique gene associations for the symptom domains. Genes associated with neurotransmitter systems and neuronal development/maintenance primarily constitute the shared associations. Needed are studies that examine the genetic basis of specific symptoms within the broader domains in addition to functional mechanisms. Such investigations are critical to developing precision treatment and care for individuals afflicted with schizophrenia.

  1. Psychopathic Personality Traits and Environmental Contexts: Differential Correlates, Gender Differences, and Genetic Mediation

    Science.gov (United States)

    Hicks, Brian M.; Carlson, Marie D.; Blonigen, Daniel M.; Patrick, Christopher J.; Iacono, William G.; MGue, Matt

    2011-01-01

    Theorists have speculated that primary psychopathy (or Factor 1 affective-interpersonal features) is prominently heritable whereas secondary psychopathy (or Factor 2 social deviance) is more environmentally determined. We tested this differential heritability hypothesis using a large adolescent twin sample. Trait-based proxies of primary and secondary psychopathic tendencies were assessed using Multidimensional Personality Questionnaire (MPQ; Tellegen & Waller, 2008) estimates of Fearless Dominance and Impulsive Antisociality, respectively (Benning et al., 2005). The environmental contexts of family, school, peers, and stressful life events were assessed using multiple raters and methods. Consistent with prior research, MPQ Impulsive Antisociality was robustly associated with each environmental risk factor, and these associations were significantly greater than those for MPQ Fearless Dominance. However, MPQ Fearless Dominance and Impulsive Antisociality exhibited similar heritability, and genetic effects mediated the associations between MPQ Impulsive Antisociality and the environmental measures. Results were largely consistent across male and female twins. We conclude that gene-environment correlations rather than main effects of genes and environments account for the differential environmental correlates of primary and secondary psychopathy. PMID:22452762

  2. The Genetic and Environmental Sources of Resemblance Between Normative Personality and Personality Disorder Traits.

    Science.gov (United States)

    Kendler, K S; Aggen, S H; Gillespie, Nathan; Neale, M C; Knudsen, G P; Krueger, R F; Czajkowski, Nikolai; Ystrom, Eivind; Reichborn-Kjennerud, T

    2017-04-01

    Recent work has suggested a high level of congruence between normative personality, most typically represented by the "big five" factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-5-Norwegian Brief Form (PID-5-NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-5-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-5-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI.

  3. Genetic and Environmental Impact on Iron, Zinc, and Phytate in Food Sorghum Grown in Benin

    NARCIS (Netherlands)

    Kayodé, A.P.P.; Linnemann, A.R.; Hounhouigan, J.D.; Nout, M.J.R.; Boekel, van M.A.J.S.

    2006-01-01

    Seventy-six farmers' varieties of sorghum from Benin were distinguished by amplified fragment length polymorphism (AFLP) and clustered into 45 distinct genotypes. The genotype clusters were evaluated for their Fe, Zn, and phytate concentrations to assess the impact of genetic and environmental

  4. The age-dependency of genetic and environmental influences on serum cytokine levels : A twin study

    NARCIS (Netherlands)

    Sas, Arthur A.; Jamshidi, Yalda; Zheng, Dongling; Wu, Ting; Korf, Jakob; Alizadeh, Behrooz Z.; Snieder, Harold; Spector, Timothy D.

    2012-01-01

    Previous epidemiologic studies have evaluated the use of immunological markers as possible tools for measuring ageing and predicting age-related pathology. The importance of both genetic and environmental influences in regulation of these markers has been emphasized. In order to further evaluate

  5. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

    Science.gov (United States)

    Hampel, Heather; Bennett, Robin L; Buchanan, Adam; Pearlman, Rachel; Wiesner, Georgia L

    2015-01-01

    The practice guidelines of the American College of Medical Genetics and Genomics (ACMG) and the National Society of Genetic Counselors (NSGC) are developed by members of the ACMG and NSGC to assist medical geneticists, genetic counselors, and other health-care providers in making decisions about appropriate management of genetic concerns, including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the ACMG and NSGC joint practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are current only as of their publication date, and are subject to change without notice as advances emerge. In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments, and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health-care provider's best medical judgment based on the clinical circumstances of a particular patient or patient population. Practice guidelines are published by the ACMG or the NSGC for educational and informational purposes only, and neither the ACMG nor the NSGC "approve" or "endorse" any specific methods, practices, or sources of information.Cancer genetic consultation is an important aspect of the care of individuals at increased risk of a hereditary cancer syndrome. Yet several patient, clinician, and system-level barriers hinder identification of individuals appropriate for cancer genetics

  6. Genetic and environmental influences on Chinese language and reading abilities.

    Directory of Open Access Journals (Sweden)

    Bonnie Wing-Yin Chow

    2011-02-01

    Full Text Available This study investigated the etiology of individual differences in Chinese language and reading skills in 312 typically developing Chinese twin pairs aged from 3 to 11 years (228 pairs of monozygotic twins and 84 pairs of dizygotic twins; 166 male pairs and 146 female pairs. Children were individually given tasks of Chinese word reading, receptive vocabulary, phonological memory, tone awareness, syllable and rhyme awareness, rapid automatized naming, morphological awareness and orthographic skills, and Raven's Coloured Progressive Matrices. All analyses controlled for the effects of age. There were moderate to substantial genetic influences on word reading, tone awareness, phonological memory, morphological awareness and rapid automatized naming (estimates ranged from .42 to .73, while shared environment exerted moderate to strong effects on receptive vocabulary, syllable and rhyme awareness and orthographic skills (estimates ranged from .35 to .63. Results were largely unchanged when scores were adjusted for nonverbal reasoning as well as age. Findings of this study are mostly similar to those found for English, a language with very different characteristics, and suggest the universality of genetic and environmental influences across languages.

  7. Genetic and Environmental Influences on Motor Function: A Magnetoencephalographic Study of Twins

    OpenAIRE

    Araki, Toshihiko; Hirata, Masayuki; Sugata, Hisato; Yanagisawa, Takufumi; Onishi, Mai; Watanabe, Yoshiyuki; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo; Yorifuji, Shiro

    2014-01-01

    To investigate the effect of genetic and environmental influences on cerebral motor function, we determined similarities and differences of movement-related cortical fields (MRCFs) in middle-aged and elderly monozygotic (MZ) twins. MRCFs were measured using a 160-channel magnetoencephalogram system when MZ twins were instructed to repeat lifting of the right index finger. We compared latency, amplitude, dipole location, and dipole intensity of movement-evoked field 1 (MEF1) between 16 MZ twin...

  8. DNA methylation in metabolic disorders

    DEFF Research Database (Denmark)

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  9. Different concepts and models of information for family-relevant genetic findings: comparison and ethical analysis.

    Science.gov (United States)

    Lenk, Christian; Frommeld, Debora

    2015-08-01

    Genetic predispositions often concern not only individual persons, but also other family members. Advances in the development of genetic tests lead to a growing number of genetic diagnoses in medical practice and to an increasing importance of genetic counseling. In the present article, a number of ethical foundations and preconditions for this issue are discussed. Four different models for the handling of genetic information are presented and analyzed including a discussion of practical implications. The different models' ranges of content reach from a strictly autonomous position over self-governed arrangements in the practice of genetic counseling up to the involvement of official bodies and committees. The different models show a number of elements which seem to be very useful for the handling of genetic data in families from an ethical perspective. In contrast, the limitations of the standard medical attempt regarding confidentiality and personal autonomy in the context of genetic information in the family are described. Finally, recommendations for further ethical research and the development of genetic counseling in families are given.

  10. Genetic and environmental etiology of stability and changes in self-esteem linked to personality: A Japanese twin study

    OpenAIRE

    Shikishima, Chizuru; Hiraishi, Kai; Takahashi, Yusuke; Yamagata, Shinji; Yamaguchi, Susumu; Ando, Juko

    2018-01-01

    This study used a behavioral genetic approach to examine the genetic and environmental etiology of stability and changes in self-esteem in relation to personality. Multiple genetic analyses were conducted on a longitudinal dataset of self-esteem and Big Five personality scores among young adult Japanese twins over the course of a decade. There were 1221 individuals for whom data were available on both self-esteem and the Big Five personality test at Time 1 and 365 at Time 2. The mean interval...

  11. Genetic and environmental influences on adult attention deficit hyperactivity disorder symptoms: a large Swedish population-based study of twins.

    Science.gov (United States)

    Larsson, H; Asherson, P; Chang, Z; Ljung, T; Friedrichs, B; Larsson, J-O; Lichtenstein, P

    2013-01-01

    Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. Family and twin studies delineate a disorder with strong genetic influences among children and adolescents based on parent- and teacher-reported data but little is known about the genetic and environmental contribution to DSM-IV ADHD symptoms in adulthood. We therefore aimed to investigate the impact of genetic and environmental influences on the inattentive and hyperactive-impulsive symptoms of ADHD in adults. Twin methods were applied to self-reported assessments of ADHD symptoms from a large population-based Swedish twin study that included data from 15 198 Swedish male and female twins aged 20 to 46 years. The broad heritability [i.e., A + D, where A is an additive genetic factor and D (dominance) a non-additive genetic factor] was 37% (A = 11%, D = 26%) for inattention and 38% (A = 18%, D = 20%) for hyperactivity-impulsivity. The results also indicate that 52% of the phenotypic correlation between inattention and hyperactivity-impulsivity (r = 0.43) was explained by genetic influences whereas the remaining part of the covariance was explained by non-shared environmental influences. These results were replicated across age strata. Our findings of moderate broad heritability estimates are consistent with previous literature on self-rated ADHD symptoms in older children, adolescents and adults and retrospective reports of self-rated childhood ADHD by adults but differ from studies of younger children with informant ratings. Future research needs to clarify whether our data indicate a true decrease in the heritability of ADHD in adults compared to children, or whether this relates to the use of self-ratings in contrast to informant data.

  12. The bipolar puzzle, adding new pieces. Factors associated with bipolar disorder, Genetic and environmental influences

    NARCIS (Netherlands)

    van der Schot, A.C.

    2009-01-01

    The focus of this thesis is twofold. The first part will discuss the structural brain abnormalities and schoolperformance associated with bipolar disorder and the influence of genetic and/or environmental factors to this association. It is part of a large twin study investigating several potential

  13. Nature Versus Nurture: Does Proteostasis Imbalance Underlie the Genetic, Environmental, and Age-Related Risk Factors for Alzheimer's Disease?

    Science.gov (United States)

    Kikis, Elise A

    2017-08-22

    Aging is a risk factor for a number of "age-related diseases", including Alzheimer's disease (AD). AD affects more than a third of all people over the age of 85, and is the leading cause of dementia worldwide. Symptoms include forgetfulness, memory loss, and cognitive decline, ultimately resulting in the need for full-time care. While there is no cure for AD, pharmacological approaches to alleviate symptoms and target underlying causes of the disease have been developed, albeit with limited success. This review presents the age-related, genetic, and environmental risk factors for AD and proposes a hypothesis for the mechanistic link between genetics and the environment. In short, much is known about the genetics of early-onset familial AD (EO-FAD) and the central role played by the Aβ peptide and protein misfolding, but late-onset AD (LOAD) is not thought to have direct genetic causes. Nonetheless, genetic risk factors such as isoforms of the protein ApoE have been identified. Additional findings suggest that air pollution caused by the combustion of fossil fuels may be an important environmental risk factor for AD. A hypothesis suggesting that poor air quality might act by disrupting protein folding homeostasis (proteostasis) is presented.

  14. Genetic and environmental relationships of metabolic and weight phenotypes to metabolic syndrome and diabetes: the healthy twin study.

    Science.gov (United States)

    Song, Yun-Mi; Sung, Joohon; Lee, Kayoung

    2015-02-01

    We aimed to examine the relationships, including genetic and environmental correlations, between metabolic and weight phenotypes and factors related to diabetes and metabolic syndrome. Participants of the Healthy Twin Study without diabetes (n=2687; 895 monozygotic and 204 dizygotic twins, and 1588 nontwin family members; mean age, 42.5±13.1 years) were stratified according to body mass index (BMI) (metabolic syndrome categories at baseline. The metabolic traits, namely diabetes and metabolic syndrome, metabolic syndrome components, glycated hemoglobin (HbA1c) level, and homeostasis model assessment of insulin resistance (HOMA-IR), were assessed after 2.5±2.1 years. In a multivariate-adjusted model, those who had metabolic syndrome or overweight phenotypes at baseline were more likely to have higher HbA1C and HOMA-IR levels and abnormal metabolic syndrome components at follow-up as compared to the metabolically healthy normal weight subgroup. The incidence of diabetes was 4.4-fold higher in the metabolically unhealthy but normal weight individuals and 3.3-fold higher in the metabolically unhealthy and overweight individuals as compared with the metabolically healthy normal weight individuals. The heritability of the metabolic syndrome/weight phenotypes was 0.40±0.03. Significant genetic and environmental correlations were observed between the metabolic syndrome/weight phenotypes at baseline and the metabolic traits at follow-up, except for incident diabetes, which only had a significant common genetic sharing with the baseline phenotypes. The genetic and environmental relationships between the metabolic and weight phenotypes at baseline and the metabolic traits at follow-up suggest pleiotropic genetic mechanisms and the crucial role of lifestyle and behavioral factors.

  15. Genetic and environmental factors influencing the Placental Growth Factor (PGF variation in two populations.

    Directory of Open Access Journals (Sweden)

    Rossella Sorice

    Full Text Available Placental Growth Factor (PGF is a key molecule in angiogenesis. Several studies have revealed an important role of PGF primarily in pathological conditions (e.g.: ischaemia, tumour formation, cardiovascular diseases and inflammatory processes suggesting its use as a potential therapeutic agent. However, to date, no information is available regarding the genetics of PGF variability. Furthermore, even though the effect of environmental factors (e.g.: cigarette smoking on angiogenesis has been explored, no data on the influence of these factors on PGF levels have been reported so far. Here we have first investigated PGF variability in two cohorts focusing on non-genetic risk factors: a study sample from two isolated villages in the Cilento region, South Italy (N=871 and a replication sample from the general Danish population (N=1,812. A significant difference in PGF mean levels was found between the two cohorts. However, in both samples, we observed a strong correlation of PGF levels with ageing and sex, men displaying PGF levels significantly higher than women. Interestingly, smoking was also found to influence the trait in the two populations, although differently. We have then focused on genetic risk factors. The association between five single nucleotide polymorphisms (SNPs located in the PGF gene and the plasma levels of the protein was investigated. Two polymorphisms (rs11850328 and rs2268614 were associated with the PGF plasma levels in the Cilento sample and these associations were strongly replicated in the Danish sample. These results, for the first time, support the hypothesis of the presence of genetic and environmental factors influencing PGF plasma variability.

  16. Genetic testing for exercise prescription and injury prevention: AIS-Athlome consortium-FIMS joint statement

    OpenAIRE

    Vlahovich, Nicole; Hughes, David C.; Griffiths, Lyn R.; Wang, Guan; Pitsiladis, Yannis P.; Pigozzi, Fabio; Bachl, Nobert; Eynon, Nir

    2017-01-01

    Background There has been considerable growth in basic knowledge and understanding of how genes are influencing response to exercise training and predisposition to injuries and chronic diseases. On the basis of this knowledge, clinical genetic tests may in the future allow the personalisation and optimisation of physical activity, thus providing an avenue for increased efficiency of exercise prescription for health and disease. Results This review provides an overview of the current status of...

  17. Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

    DEFF Research Database (Denmark)

    Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S

    2018-01-01

    Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns...... the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes...... in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely...

  18. Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

    Science.gov (United States)

    Obermayer-Pietsch, Barbara M; Bonelli, Christine M; Walter, Daniela E; Kuhn, Regina J; Fahrleitner-Pammer, Astrid; Berghold, Andrea; Goessler, Walter; Stepan, Vinzenz; Dobnig, Harald; Leb, Georg; Renner, Wilfried

    2004-01-01

    Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose

  19. A predisposition for allergies predicts subsequent hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder: a nationwide longitudinal study.

    Science.gov (United States)

    Chen, Mu-Hong; Li, Cheng-Ta; Lin, Wei-Chen; Wei, Hang-Tin; Chang, Wen-Han; Chen, Tzeng-Ji; Pan, Tai-Long; Su, Tung-Ping; Bai, Ya-Mei

    2014-10-01

    Previous studies have shown that both severe mental disorders (schizophrenia and bipolar disorder) and atopic diseases were associated with an increased risk of metabolic syndrome. However, the role of atopy/the predisposition for allergies in the development of metabolic syndrome is still unknown among those with severe mental disorders. Using the Taiwan National Health Insurance Research Database, 5826 patients with schizophrenia or bipolar disorder (1908 with a predisposition for allergies and 3918 without) were enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia, and/or diabetes mellitus were identified during the follow-up to the end of 2011. A predisposition for allergies increased the risk of developing hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR: 1.37) in later life among those with severe mental disorders. A dose-dependent relationship was noted between having more atopic comorbidities and a greater likelihood of hypertension (1 atopic disease: HR: 1.60; ≧ 2 atopic comorbidities: HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26; HR: 1.69). A predisposition for allergies was an independent risk factor for hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder. Further studies would be required to elucidate the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and metabolic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Seascape genetics along environmental gradients in the Arabian Peninsula: insights from ddRAD sequencing of anemonefishes

    KAUST Repository

    Saenz Agudelo, Pablo

    2015-11-17

    Understanding the processes that shape patterns of genetic structure across space is a central aim of landscape genetics. However, it remains unclear how geographic features and environmental variables shape gene flow, particularly for marine species in large complex seascapes. Here, we evaluated the genomic composition of the two-band anemonefish Amphiprion bicinctus across its entire geographic range in the Red Sea and Gulf of Aden, as well as its close relative, Amphiprion omanensis endemic to the southern coast of Oman. Both the Red Sea and the Arabian Sea are complex and environmentally heterogeneous marine systems that provide an ideal scenario to address these questions. Our findings confirm the presence of two genetic clusters previously reported for A. bicinctus in the Red Sea. Genetic structure analyses suggest a complex seascape configuration, with evidence of both Isolation by Distance (IBD) and Isolation by Environment (IBE). In addition to IBD and IBE, genetic structure among sites was best explained when two barriers to gene flow were also accounted for. One of these coincides with a strong oligotrophic-eutrophic gradient at around 16-20˚N in the Red Sea. The other agrees with an historical bathymetric barrier at the straight of Bab al Mandab. Finally, these data support the presence of inter-specific hybrids at an intermediate suture zone at Socotra and indicate complex patterns of genomic admixture in the Gulf of Aden with evidence of introgression between species. Our findings highlight the power of recent genomic approaches to resolve subtle patterns of gene flow in marine seascapes.

  1. Seascape genetics along environmental gradients in the Arabian Peninsula: insights from ddRAD sequencing of anemonefishes

    KAUST Repository

    Saenz Agudelo, Pablo; DiBattista, Joseph; Piatek, Marek J.; Gaither, Michelle R.; Harrison, Hugo B.; Nanninga, Gerrit B.; Berumen, Michael L.

    2015-01-01

    Understanding the processes that shape patterns of genetic structure across space is a central aim of landscape genetics. However, it remains unclear how geographic features and environmental variables shape gene flow, particularly for marine species in large complex seascapes. Here, we evaluated the genomic composition of the two-band anemonefish Amphiprion bicinctus across its entire geographic range in the Red Sea and Gulf of Aden, as well as its close relative, Amphiprion omanensis endemic to the southern coast of Oman. Both the Red Sea and the Arabian Sea are complex and environmentally heterogeneous marine systems that provide an ideal scenario to address these questions. Our findings confirm the presence of two genetic clusters previously reported for A. bicinctus in the Red Sea. Genetic structure analyses suggest a complex seascape configuration, with evidence of both Isolation by Distance (IBD) and Isolation by Environment (IBE). In addition to IBD and IBE, genetic structure among sites was best explained when two barriers to gene flow were also accounted for. One of these coincides with a strong oligotrophic-eutrophic gradient at around 16-20˚N in the Red Sea. The other agrees with an historical bathymetric barrier at the straight of Bab al Mandab. Finally, these data support the presence of inter-specific hybrids at an intermediate suture zone at Socotra and indicate complex patterns of genomic admixture in the Gulf of Aden with evidence of introgression between species. Our findings highlight the power of recent genomic approaches to resolve subtle patterns of gene flow in marine seascapes.

  2. Enhanced computational methods for quantifying the effect of geographic and environmental isolation on genetic differentiation

    NARCIS (Netherlands)

    Botta, Filippo; Eriksen, Casper; Fontaine, Michael Christophe; Guillot, Gilles

    2015-01-01

    In a recent paper, Bradburd et al. (2013) proposed a model to quantify the relative effect ofgeographic and environmental distance on genetic differentiation. Here, we enhance this method in several ways. 1. We modify the covariance model so as to fit better with mainstream geostatistical models and

  3. Long-term effects of an inpatient weight-loss program in obese children and the role of genetic predisposition-rationale and design of the LOGIC-trial.

    Science.gov (United States)

    Rank, Melanie; Siegrist, Monika; Wilks, Désirée C; Haller, Bernhard; Wolfarth, Bernd; Langhof, Helmut; Halle, Martin

    2012-03-19

    -term effects of an inpatient weight-loss program, this study will contribute to a better understanding of inter-individual differences in the regulation of body weight, taking into account the role of genetic predisposition and lifestyle factors. NCT01067157.

  4. Genetic and Environmental Structure of DSM-IV Criteria for Antisocial Personality Disorder: A Twin Study.

    Science.gov (United States)

    Rosenström, Tom; Ystrom, Eivind; Torvik, Fartein Ask; Czajkowski, Nikolai Olavi; Gillespie, Nathan A; Aggen, Steven H; Krueger, Robert F; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

    2017-05-01

    Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI 40-67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct.

  5. Genetic and environmental effects on same-sex sexual behavior: a population study of twins in Sweden.

    Science.gov (United States)

    Långström, Niklas; Rahman, Qazi; Carlström, Eva; Lichtenstein, Paul

    2010-02-01

    There is still uncertainty about the relative importance of genes and environments on human sexual orientation. One reason is that previous studies employed self-selected, opportunistic, or small population-based samples. We used data from a truly population-based 2005-2006 survey of all adult twins (20-47 years) in Sweden to conduct the largest twin study of same-sex sexual behavior attempted so far. We performed biometric modeling with data on any and total number of lifetime same-sex sexual partners, respectively. The analyses were conducted separately by sex. Twin resemblance was moderate for the 3,826 studied monozygotic and dizygotic same-sex twin pairs. Biometric modeling revealed that, in men, genetic effects explained .34-.39 of the