Clinical and prognostic significance of genetic factors in recurrent in-vitro fertilization failures

Directory of Open Access Journals (Sweden)

Zeynep Ocak

2013-09-01

Full Text Available In 1978, a new era has started in the treatment of infertility by the birth of the first baby from a pregnancy achieved by in-vitro fertilization. Following this, healthy pregnancies have been achieved by assisted reproductive techniques such as in-vitro fertilization by an important percentage of the childless couples. Despite all developments in assisted reproductive techniques, pregnancy rates haven’t increased as expected, and unfortunately the rate of implantation success of transferred embryos remained at low levels (15%. Similar to recurrent pregnancy loss in which the etiology is not clear yet and the causes are probably multifactorial, evaluation of patients with recurrent implantation failure is difficult and complex. Genetic risk factors such as genomic rearrangements in the couples and the embryo, sperm DNA damage and imprinting defects have been considered among the causes of recurrent implantation failure. Genetic screening is an integral part of providing good medical care of patients and families receiving a diagnosis of a genetic disorder. The aim of preconceptional genetic screening is to asses the fertility, to be able to increase succes rate of infertility treatments and to detect the healthy carriers who may have a baby with the risk of fatal and/or multiple congenital anomalies. In this review, possible genetic factors associated with recurrent implantation failure are discussed in the light of the current literature.

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...

Digging up the recent Spanish memory: genetic identification of human remains from mass graves of the Spanish Civil War and posterior dictatorship.

Science.gov (United States)

Baeta, Miriam; Núñez, Carolina; Cardoso, Sergio; Palencia-Madrid, Leire; Herrasti, Lourdes; Etxeberria, Francisco; de Pancorbo, Marian M

2015-11-01

The Spanish Civil War (1936-1939) and posterior dictatorship (until 1970s) stands as one of the major conflicts in the recent history of Spain. It led to nearly two hundred thousand men and women executed or murdered extra-judicially or after dubious legal procedures. Nowadays, most of them remain unidentified or even buried in irretraceable mass graves across Spain. Here, we present the genetic identification of human remains found in 26 mass graves located in Northern Spain. A total of 252 post-mortem remains were analyzed and compared to 186 relatives, allowing the identification of 87 victims. Overall, a significant success of DNA profiling was reached, since informative profiles (≥ 12 STRs and/or mitochondrial DNA profile) were obtained in 85.71% of the remains. This high performance in DNA profiling from challenging samples demonstrated the efficacy of DNA extraction and amplification methods used herein, given that only around 14.29% of the samples did not provide an informative genetic profile for the analysis performed, probably due to the presence of degraded and/or limited DNA in these remains. However, this study shows a partial identification success rate, which is clearly a consequence of the lack of both appropriate family members for genetic comparisons and accurate information about the victims' location. Hence, further perseverance in the exhumation of other intact graves as well as in the search of more alleged relatives is crucial in order to facilitate and increase the number of genetic identifications. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Risk factors for Alzheimer's disease : a genetic-epidemiologic study

NARCIS (Netherlands)

C.M. van Duijn (Cornelia)

1992-01-01

textabstractThe work presented in this thesis has been motivated by the Jack of knowledge of risk factors for Alzheimer's disease. It has been long recognised that genetic factors are implicated, in particular in early-onset Alzheimer's disease.4 But to what extent are genetic factors involved?

Genetic and non-iodine-related factors in the aetiology of nodular goitre.

Science.gov (United States)

Knudsen, Nils; Brix, Thomas Heiberg

2014-08-01

Genetic and a large number of environmental non-iodine-related factors play a role in the cause of nodular goitre. Most evidence for the influence of genetic and environmental factors in the cause of goitre is from cross-sectional, population-based studies. Only a few studies have included prospective data on risk factors for nodular goitre, although few prospective data are available on the effect of iodine and tobacco smoking on goitre development. Goitre is not one single phenotype. Many epidemiological studies do not distinguish diffuse from nodular goitre, as the investigated parameter is often thyroid volume or frequency with increased thyroid volume. Moreover, information on the presence and effect of gene-environment, gene-gene, and environment-environment effect modifications is limited. Thus, firm conclusions about the relative contributions and causality of the investigated risk factors should be made with caution. Smoking seems to be an established risk factor for nodular goitre, possibly with effect modification from iodine intake, as the risk associated with smoking is smaller or absent in areas with sufficient iodine intake. The use of oral contraceptives might have protective effects against goitre, and childbirth is an increased risk factor for goitre in areas with non-optimal iodine intake. Insulin resistance is a recently investigated risk factor, and the risk of goitre may be reversible with metformin treatment. Iodine remains the major environmental risk factor for nodular goitre. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human genetic factors in tuberculosis: an update.

Science.gov (United States)

van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

2017-09-01

Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

Genetic transformation of fruit trees: current status and remaining challenges.

Science.gov (United States)

Gambino, Giorgio; Gribaudo, Ivana

2012-12-01

Genetic transformation has emerged as a powerful tool for genetic improvement of fruit trees hindered by their reproductive biology and their high levels of heterozygosity. For years, genetic engineering of fruit trees has focussed principally on enhancing disease resistance (against viruses, fungi, and bacteria), although there are few examples of field cultivation and commercial application of these transgenic plants. In addition, over the years much work has been performed to enhance abiotic stress tolerance, to induce modifications of plant growth and habit, to produce marker-free transgenic plants and to improve fruit quality by modification of genes that are crucially important in the production of specific plant components. Recently, with the release of several genome sequences, studies of functional genomics are becoming increasingly important: by modification (overexpression or silencing) of genes involved in the production of specific plant components is possible to uncover regulatory mechanisms associated with the biosynthesis and catabolism of metabolites in plants. This review focuses on the main advances, in recent years, in genetic transformation of the most important species of fruit trees, devoting particular attention to functional genomics approaches and possible future challenges of genetic engineering for these species in the post-genomic era.

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

Factors influencing home care nurse intention to remain employed.

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Tourangeau, Ann; Patterson, Erin; Rowe, Alissa; Saari, Margaret; Thomson, Heather; MacDonald, Geraldine; Cranley, Lisa; Squires, Mae

2014-11-01

To identify factors affecting Canadian home care nurse intention to remain employed (ITR). In developed nations, healthcare continues to shift into community settings. Although considerable research exists on examining nurse ITR in hospitals, similar research related to nurses employed in home care is limited. In the face of a global nursing shortage, it is important to understand the factors influencing nurse ITR across healthcare sectors. A qualitative exploratory descriptive design was used. Focus groups were conducted with home care nurses. Data were analysed using qualitative content analysis. Six categories of influencing factors were identified by home care nurses as affecting ITR: job characteristics; work structures; relationships/communication; work environment; nurse responses to work; and employment conditions. Findings suggest the following factors influence home care nurse ITR: having autonomy; flexible scheduling; reasonable and varied workloads; supportive work relationships; and receiving adequate pay and benefits. Home care nurses did not identify job satisfaction as a single concept influencing ITR. Home care nursing management should support nurse autonomy, allow flexible scheduling, promote reasonable workloads and create opportunities for team building that strengthen supportive relationships among home care nurses and other health team members. © 2013 John Wiley & Sons Ltd.

[Genetic factors in myocardial infarction].

Science.gov (United States)

Hara, Masahiko; Sakata, Yasuhiko; Sato, Hiroshi

2013-02-01

One of the main mechanisms of acute myocardial infarction (AMI) is plaque rupture or erosion followed by intraluminal thrombus formation and occlusion of the coronary arteries. Thus far, many underlying conditions or environmental factors, such as hypertension, diabetes, dyslipidemia, smoking or obesity, as well as a family history of coronary artery diseases have been identified as risks for the onset of AMI. These risks suggest that AMI occurs due to interactions between underlying conditions and multiple genetic susceptibilities. For this reason, many target gene-disease association studies have been performed with the recent introduction of genome-wide association studies (GWAS) that have further revealed new genetic susceptibilities for AMI. GWAS is a way to examine many common genetic variants in different individuals to see if any variant is associated with a trait in a case-control fashion, and typically focuses on associations between single-nucleotide polymorphisms (SNP) and traits. SNP on chromosome 9p21 is one of the robust susceptibility variants for AMI which has been identified by many GWAS. In this review, we overview the methodology of GWAS, introduce genetic variants identified by GWAS as those with susceptibility for AMI, and describe the foresight of using GWAS to investigate genetic susceptibility to AMI.

Genetic factors and molecular mechanisms in dry eye disease.

Science.gov (United States)

Lee, Ling; Garrett, Qian; Flanagan, Judith; Chakrabarti, Subhabrata; Papas, Eric

2018-04-01

Dry eye disease (DED) is a complex condition with a multifactorial etiology that can be difficult to manage successfully. While external factors are modifiable, treatment success is limited if genetic factors contribute to the disease. The purpose of this review is to compile research describing normal and abnormal ocular surface function on a molecular level, appraise genetic studies involving DED or DED-associated diseases, and introduce the basic methods used for conducting genetic epidemiology studies. Copyright © 2018 Elsevier Inc. All rights reserved.

The Genetic and Environmental Factors for Keratoconus

Directory of Open Access Journals (Sweden)

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.

Evaluation of the role of genetic factors in human radioresistance

International Nuclear Information System (INIS)

Telnov, Vitaliy I.; Sotnik, Natalie V.

2002-01-01

This study was focused on evaluation of the role of genetic factors in development of chronic radiation sickness (CRS) due to occupational exposure to external γ -rays. This study was based on results of molecular-genetic studies for 985 nuclear workers of the Mayak Production Association. CRS occurrence was related to the genetic haptoglobin (Hp) system among a number of studied genetic markers. Excess risk of CRS was revealed at similar exposure doses for individuals-carriers of Hp 2-2 (1.96) versus lower risks for carriers of Hp 1-1 and 2-1 (0.64). The contribution of genetic factors to CRS development was implemented in a rather narrow dose range, i.e. it was of a relative nature. A scheme of the relationship of affecting factor and differences in genetic radioresistance was presented in terms of deterministic effects. The obtained data did not confirm the idea that A-bomb survivors were more radioresistant, thus being not representative for radiation risk estimation

New Genetic Susceptibility Factors for Sjögren's Syndrome Revealed

Science.gov (United States)

... Spotlight on Research Spotlight on Research New Genetic Susceptibility Factors for Sjögren’s Syndrome Revealed By Kirstie Saltsman, ... swallowing and speaking. “The identification of these genetic susceptibility factors opens up new avenues for understanding how ...

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids.

Science.gov (United States)

Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-06-18

To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (Pconstipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (Phospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

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.

Identification of Variants of Hepatitis C Virus (HCV Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

Directory of Open Access Journals (Sweden)

Baptiste Fouquet

Full Text Available Hepatitis C virus (HCV causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU infected by human immunodeficiency virus type 1 (HIV-1 are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1 gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.

Exploration of genetic susceptibility factors for Parkinson's disease ...

Indian Academy of Sciences (India)

1Neurosciences Research Group, School of Medicine and Institute of Genetics, Universidad Nacional de Colombia, Bogotá ... factors for Parkinson's disease in a South American sample. J. Genet. 89, ... In the current work, we report the results of a system- ..... Synaptic dysfunction and oxidative stress in Alzheimer's disease:.

Exploration of genetic susceptibility factors for Parkinson's disease

Indian Academy of Sciences (India)

Home; Journals; Journal of Genetics; Volume 89; Issue 2. Exploration of genetic susceptibility factors for Parkinson's disease in a South American sample. Bruno A. Benitez Diego A. Forero Gonzalo H. Arboleda Luis A. Granados Juan J. Yunis William Fernandez Humberto Arboleda. Research Note Volume 89 Issue 2 ...

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

Genetic and epigenetic factors: Role in male infertility

Directory of Open Access Journals (Sweden)

M B Shamsi

2011-01-01

Full Text Available Genetic factors contribute upto 15%-30% cases of male infertility. Formation of spermatozoa occurs in a sequential manner with mitotic, meiotic, and postmeiotic differentiation phases each of which is controlled by an intricate genetic program. Genes control a variety of physiologic processes, such as hypothalamus-pituitary-gonadal axis, germ cell development, and differentiation. In the era of assisted reproduction technology, it is important to understand the genetic basis of infertility to provide maximum adapted therapeutics and counseling to the couple.

Genetics and tumor genomics in familial colorectal cancer

NARCIS (Netherlands)

Middeldorp, Janneke Willemijn

2010-01-01

Colorectal cancer (CRC) is one of the most common cancers in the Western world and in about 30% hereditary factors play a role. Although several genetic factors that predispose families to CRC are known, in many families affected with CRC the underlying genetics remain elusive. The work described in

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.

The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes.

Science.gov (United States)

Łuczyński, Włodzimierz; Głowińska-Olszewska, Barbara; Bossowski, Artur

2016-10-01

The exact cause of the obesity epidemic remains unknown; however, both environmental and genetic factors are involved. People at risk of developing obesity include children with type 1 diabetes mellitus (T1DM), which in turn increases their cardiovascular disease risk. Here, we discuss the clinical and genetic factors influencing weight in patients with T1DM. In children with T1DM, the presence of obesity depends mainly on sex, metabolic control, and disease duration. However, genetic factors, including the fat mass and obesity-associated (FTO) gene, are also associated with body weight. Indeed, children with the FTO gene rs9939609 obesity-risk allele (homozygous = AA or heterozygous = AT) are predisposed to a higher body mass index and have a greater risk of being overweight or obese. However, in this review, we show that FTO gene polymorphisms only have a small effect on body weight in children, much weaker than the effect of clinical factors. The association between FTO gene polymorphisms and body weight is only statistically significant in children without severe obesity. Moreover, other genetic factors had no effect on weight in patients with T1DM, and further research involving larger populations is required to confirm the genetic basis of diabetes and obesity. Therefore, identifying the clinical features of children with T1DM, such as their initial body mass index, sex, metabolic control, and disease duration, will still have the strongest effect on reducing risk factors for cardiovascular diseases. Physicians should pay close attention to modifiable elements of these relationships, for example, metabolic control and energy and insulin intake, when caring for patients with T1DM. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Moderation of genetic factors by parental divorce in adolescents' evaluations of family functioning and subjective wellbeing.

Science.gov (United States)

van der Aa, Niels; Boomsma, Dorret I; Rebollo-Mesa, Irene; Hudziak, James J; Bartels, Meike

2010-04-01

Adolescents' evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.

Host genetic risk factors for West Nile virus infection and disease progression.

Directory of Open Access Journals (Sweden)

Abigail W Bigham

Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids

Science.gov (United States)

Laugsand, Eivor A; Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål

2015-01-01

Objectives: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. Methods: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). Results: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini–Hochberg criterion for a 10% false discovery rate. Conclusions: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment. PMID:26087058

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.

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.

On the Road to Genetic Boolean Matrix Factorization

Czech Academy of Sciences Publication Activity Database

Snášel, V.; Platoš, J.; Krömer, P.; Húsek, Dušan; Frolov, A.

2007-01-01

Roč. 17, č. 6 (2007), s. 675-688 ISSN 1210-0552 Institutional research plan: CEZ:AV0Z10300504 Keywords : data mining * genetic algorithms * Boolean factorization * binary data * machine learning * feature extraction Subject RIV: IN - Informatics, Computer Science Impact factor: 0.280, year: 2007

Review of patient decision-making factors and attitudes regarding preimplantation genetic diagnosis.

Science.gov (United States)

Genoff Garzon, M C; Rubin, L R; Lobel, M; Stelling, J; Pastore, L M

2017-11-09

The increasing technical complexity and evolving options for repro-genetic testing have direct implications for information processing and decision making, yet the research among patients considering preimplantation genetic diagnosis (PGD) is narrowly focused. This review synthesizes the literature regarding patient PGD decision-making factors, and illuminates gaps for future research and clinical translation. Twenty-five articles met the inclusion criteria for evaluating experiences and attitudes of patients directly involved in PGD as an intervention or considering using PGD. Thirteen reports were focused exclusively on a specific disease or condition. Five themes emerged: (1) patients motivated by prospects of a healthy, genetic-variant-free child, (2) PGD requires a commitment of time, money, energy and emotions, (3) patients concerned about logistics and ethics of discarding embryos, (4) some patients feel sense of responsibility to use available technologies, and (5) PGD decisions are complex for individuals and couples. Patient research on PGD decision-making processes has very infrequently used validated instruments, and the data collected through both quantitative and qualitative designs have been inconsistent. Future research for improving clinical counseling is needed to fill many gaps remaining in the literature regarding this decision-making process, and suggestions are offered. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors Influencing Urban Consumers' Acceptance of Genetically Modified Foods

OpenAIRE

Jae-Hwan Han; R. Wes Harrison

2007-01-01

Linkages between consumer beliefs and attitudes regarding the risks and benefits of genetically modified foods and consumer purchase intentions for these foods are examined. Factors that hinder consumer purchases of genetically modified foods are also tested. Results show that purchase intentions for consumers willing to buy genetically modified crops and meats are primarily affected by their belief that these foods are safe. On the other hand, intentions of consumers who decide not to buy ge...

Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered.

Science.gov (United States)

Richards, Gary D

2006-11-01

A new species, Homo floresiensis, was recently named for Pleistocene hominid remains on Flores, Indonesia. Significant controversy has arisen regarding this species. To address controversial issues and refocus investigations, I examine the affinities of these remains with Homo sapiens. Clarification of problematic issues is sought through an integration of genetic and physiological data on brain ontogeny and evolution. Clarification of the taxonomic value of various 'primitive' traits is possible given these data. Based on this evidence and using a H. sapiens morphological template, models are developed to account for the combination of features displayed in the Flores fossils. Given this overview, I find substantial support for the hypothesis that the remains represent a variant of H. sapiens possessing a combined growth hormone-insulin-like growth factor I axis modification and mutation of the MCPH gene family. Further work will be required to determine the extent to which this variant characterized the population.

Molecular genetic analysis on the remains of the Dark Countess: Revisiting the French Royal family.

Science.gov (United States)

Parson, Walther; Berger, Cordula; Sänger, Timo; Lutz-Bonengel, Sabine

2015-11-01

The "Dark Counts" were a mysterious couple that appeared in the Thuringian village Eishausen in 1807. After living in self imposed solitude for 30 years the woman died and was buried under the name Sophia Botta. Her companion, who presented himself as Vavel de Versay, died in 1845 and was later identified as Leonardus Cornelius van der Valck, secretary of the Dutch embassy in Paris. Their lifestyle led to speculations that she was the true princess Marie Thérèse Charlotte of France, daughter of Louis XVI and Marie Antoinette. According to these speculations she was substituted by another young woman on a voyage from Paris to Vienna. Molecular genetic analyses were set out to test the remains attributed to the Dark Countess. Mitochondrial DNA testing brought concordant results determined in two forensic laboratories (Innsbruck, Austria and Freiburg, Germany) on parallel samples of the remains. The results were in exclusion to both, the mitochondrial lineage earlier reported for the French Royal family and the mitochondrial haplotype observed in a living descendant of the Royal family. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Brachial plexus palsy and shoulder dystocia: obstetric risk factors remain elusive.

Science.gov (United States)

Ouzounian, Joseph G; Korst, Lisa M; Miller, David A; Lee, Richard H

2013-04-01

Shoulder dystocia (SD) and brachial plexus palsy (BPP) are complications of childbirth that can result in significant long-term sequelae. The purpose of the present study was to analyze risk factors in cases of SD and BPP. We performed a retrospective study of laboring women who delivered a singleton, term, live-born infant at the Los Angeles County + University of Southern California Medical Center from 1995 to 2004. Multivariable logistic regression models were used to analyze risk factors among SD cases with and without BPP. Of the 13,998 deliveries that met inclusion criteria, 221 (1.6%) had SD. Of these, 42 (19.0%) had BPP. After testing for association with multiple potential risk factors, including maternal demographic variables, diabetes, hypertension, prior cesarean delivery, uterine abnormalities, induction of labor, prolonged second stage (adjusted by parity and epidural use), assisted vaginal delivery, and neonatal birth weight, no statistical association of BPP with any specific risk factor was identified. In the present study, we were unable to identify any reliable risk factors for BPP among deliveries with or without SD. SD and BPP remain unpredictable complications of childbirth. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetic transformation of barley: limiting factors

Czech Academy of Sciences Publication Activity Database

Vyroubalová, Š.; Šmehilová, M.; Galuszka, P.; Ohnoutková, Ludmila

2011-01-01

Roč. 55, č. 2 (2011), s. 213-224 ISSN 0006-3134 R&D Projects: GA ČR GD522/08/H003; GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z50380511 Keywords : Agrobacterium * albinism * Hordeum Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.974, year: 2011

Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease.

Science.gov (United States)

Kanatsu, Kunihiko; Tomita, Taisuke

2017-01-01

Alzheimer disease (AD) is a neurodegenerative disease characterized by the extensive deposition of senile plaques and neurofibrillary tangles. Until recently, only the APOE gene had been known as a genetic risk factor for late-onset AD (LOAD), which accounts for more than 95% of all AD cases. However, in addition to this well-established genetic risk factor, genome-wide association studies have identified several single nucleotide polymorphisms as genetic risk factors of LOAD, such as PICALM and BIN1 . In addition, whole genome sequencing and exome sequencing have identified rare variants associated with LOAD, including TREM2 . We review the recent findings related to the molecular mechanisms by which these genetic risk factors contribute to AD, and our perspectives regarding the etiology of AD for the development of therapeutic agents.

On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors.

Science.gov (United States)

Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill M; Génin, Emmanuelle

2010-01-01

Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for genetic factors. A test comparing the recurrence risks in sibs according to the exposure of indexes is proposed and its power is studied for varying values of model parameters. The Exposed versus Unexposed Recurrence Analysis (EURECA) is valuable for common diseases with moderate familial aggregation, only when the role of exposure has been clearly outlined. Interestingly, accounting for a sibling correlation for the exposure increases the power of EURECA. An application on a sample ascertained through one index affected with type 2 diabetes is presented where gene-environment interactions involving obesity and physical inactivity are investigated. Association of obesity with type 2 diabetes is clearly evidenced and a potential interaction involving this factor is suggested in Hispanics (P=0.045), whereas a clear gene-environment interaction is evidenced involving physical inactivity only in non-Hispanic whites (P=0.028). The proposed method might be of particular interest before genetic studies to help determine the environmental risk factors that will need to be accounted for to increase the power to detect genetic risk factors and to select the most appropriate samples to genotype.

Intrauterine and genetic factors in early childhood sensitization

DEFF Research Database (Denmark)

Bønnelykke, Klaus

2010-01-01

The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... with production of specific IgE-antibodies against allergens. Sensitization may cause allergic symptoms, and sensitization early in life is a strong risk factor for later disease. Fetal and early postnatal life seems to be a critical period for development of atopic disease and may be an important “window...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...

Genetic and non-genetic factors affecting body weight in Tellicherry ...

African Journals Online (AJOL)

VCRI_AN_GENETICS

Abstract. Data on 566 Tellicherry goats, recorded between 1988 and 2007 were used to study the effect of non- genetic factors on body weight and daily gain from birth to 12 months of age. The least-squares means for body weight at birth and at 12 months of age were 2.17 ± 0.03 and 18.78 ± 0.44 kg, respectively. The pre-.

Genetic factors explain half of all variance in serum eosinophil cationic protein

DEFF Research Database (Denmark)

Elmose, Camilla; Sverrild, Asger; van der Sluis, Sophie

2014-01-01

with variation in serum ECP and to determine the relative proportion of the variation in ECP due to genetic and non-genetic factors, in an adult twin sample. METHODS: A sample of 575 twins, selected through a proband with self-reported asthma, had serum ECP, lung function, airway responsiveness to methacholine......, exhaled nitric oxide, and skin test reactivity, measured. Linear regression analysis and variance component models were used to study factors associated with variation in ECP and the relative genetic influence on ECP levels. RESULTS: Sex (regression coefficient = -0.107, P ... was statistically non-significant (r = -0.11, P = 0.50). CONCLUSION: Around half of all variance in serum ECP is explained by genetic factors. Serum ECP is influenced by sex, BMI, and airway responsiveness. Serum ECP and airway responsiveness seem not to share genetic variance....

Abiotic and Biotic Factors Regulating Inter-Kingdom Engagement between Insects and Microbe Activity on Vertebrate Remains

Science.gov (United States)

Jordan, Heather R.; Tomberlin, Jeffery K.

2017-01-01

A number of abiotic and biotic factors are known to regulate arthropod attraction, colonization, and utilization of decomposing vertebrate remains. Such information is critical when assessing arthropod evidence associated with said remains in terms of forensic relevance. Interactions are not limited to just between the resource and arthropods. There is another biotic factor that has been historically overlooked; however, with the advent of high-throughput sequencing, and other molecular techniques, the curtain has been pulled back to reveal a microscopic world that is playing a major role with regards to carrion decomposition patterns in association with arthropods. The objective of this publication is to review many of these factors and draw attention to their impact on microbial, specifically bacteria, activity associated with these remains as it is our contention that microbes serve as a primary mechanism regulating associated arthropod behavior. PMID:28538664

Genetic factors in Threatened Species Recovery Plans on three continents

Science.gov (United States)

Threatened species' recovery planning is applied globally to stem the current species extinction crisis. Evidence supports a key role of genetic processes, such as inbreeding depression, in determining species viability. We examined whether genetic factors are considered in threa...

Genetic factors influencing ferritin levels in 14,126 blood donors

DEFF Research Database (Denmark)

Sørensen, Erik; Rigas, Andreas S; Thørner, Lise W

2015-01-01

BACKGROUND: Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. STUDY DESIGN...... AND METHODS: The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain...... with iron deficiency in women. Results for all other genetic variants were insignificant. CONCLUSION: Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron...

Genetics of infectious diseases: hidden etiologies and common pathways.

Science.gov (United States)

Orlova, Marianna; Di Pietrantonio, Tania; Schurr, Erwin

2011-09-01

Since the completion of the human genome sequence, the study of common genetic polymorphisms in complex human diseases has become a main activity of human genetics. Employing genome-wide association studies, hundreds of modest genetic risk factors have been identified. In infectious diseases the identification of common risk factors has been varied and as in other common diseases it seems likely that important genetic risk factors remain to be discovered. Nevertheless, the identification of disease-specific genetic risk factors revealed an unexpected overlap in susceptibility genes of diverse inflammatory and infectious diseases. Analysis of the multi-disease susceptibility genes has allowed the definition of shared key pathways of inflammatory dysregulation and suggested unexpected infectious etiologies for other "non-infectious" common diseases.

A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

Science.gov (United States)

Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

2009-12-01

Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors. 2009 Wiley-Liss, Inc.

Genetic Causes of Recurrent Pregnancy Loss.

Science.gov (United States)

Page, Jessica M; Silver, Robert M

2016-09-01

Pregnancy loss is one of the most common obstetric complications, affecting over 30% of conceptions. A considerable proportion of losses are due to genetic abnormalities. Indeed, over 50% of early pregnancy losses have been associated with chromosomal abnormalities. Most are due to de novo nondisjunctional events but balanced parental translocations are responsible for a small but important percentage of genetic abnormalities in couples with recurrent pregnancy loss. In the past, assessment of genetic abnormalities was limited to karyotype performed on placental or fetal tissue. However, advances in molecular genetic technology now provide rich genetic information about additional genetic causes of and risk factors for pregnancy loss. In addition, the use of preimplantation genetic testing in couples undergoing in vitro fertilization has the potential to decrease the risk of pregnancy loss from genetic abnormalities. To date, efficacy is uncertain but considerable potential remains. This chapter will review what is known about genetic causes of recurrent pregnancy loss with a focus on novel causes and potential treatments. Remaining knowledge gaps will be highlighted.

Current status, future opportunities, and remaining challenges in landscape genetics [Chapter 14

Science.gov (United States)

Niko Balkenhol; Samuel A. Cushman; Lisette P. Waits; Andrew Storfer

2016-01-01

Landscape genetics has advanced the field of evolutionary ecology by providing a direct focus on relationships between landscape patterns and population processes, such as gene flow, selection, and genetic drift. This chapter discusses the current and emerging challenges and opportunities, which focus and facilitate future progress in the field. It presents ten...

Intrauterine and genetic factors in early childhood sensitization

DEFF Research Database (Denmark)

Bønnelykke, Klaus

2010-01-01

The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... and identifying the environmental risk factors interacting with this genetic susceptibility and the age at which intervention should be initiated. We found a FLG-associated pattern of atopic disease in early childhood characterized by early onset of eczema, early onset of asthma with severe exacerbations...... a subtype of disease where skin barrier dysfunction leads to early eczema, early asthma symptoms and later sensitization. Future FLG-targeted research has the potential of improving understanding prevention and treatment of atopic diseases in childhood....

Strong genetic overlap between executive functions and intelligence.

Science.gov (United States)

Engelhardt, Laura E; Mann, Frank D; Briley, Daniel A; Church, Jessica A; Harden, K Paige; Tucker-Drob, Elliot M

2016-09-01

Executive functions (EFs) are cognitive processes that control, monitor, and coordinate more basic cognitive processes. EFs play instrumental roles in models of complex reasoning, learning, and decision making, and individual differences in EFs have been consistently linked with individual differences in intelligence. By middle childhood, genetic factors account for a moderate proportion of the variance in intelligence, and these effects increase in magnitude through adolescence. Genetic influences on EFs are very high, even in middle childhood, but the extent to which these genetic influences overlap with those on intelligence is unclear. We examined genetic and environmental overlap between EFs and intelligence in a racially and socioeconomically diverse sample of 811 twins ages 7 to 15 years (M = 10.91, SD = 1.74) from the Texas Twin Project. A general EF factor representing variance common to inhibition, switching, working memory, and updating domains accounted for substantial proportions of variance in intelligence, primarily via a genetic pathway. General EF continued to have a strong, genetically mediated association with intelligence even after controlling for processing speed. Residual variation in general intelligence was influenced only by shared and nonshared environmental factors, and there remained no genetic variance in general intelligence that was unique of EF. Genetic variance independent of EF did remain, however, in a more specific perceptual reasoning ability. These results provide evidence that genetic influences on general intelligence are highly overlapping with those on EF. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Molecular genetic identification of skeletal remains of apartheid ...

African Journals Online (AJOL)

The Truth and Reconciliation Commission made significant progress in examining abuses committed during the apartheid era in South Africa. Despite information revealed by the commission, a large number of individuals remained missing when the commission closed its proceedings. This provided the impetus for the ...

Genetic basis of atrial fibrillation

Directory of Open Access Journals (Sweden)

Oscar Campuzano

2016-12-01

Full Text Available Atrial fibrillation is the most common sustained arrhythmia and remains as one of main challenges in current clinical practice. The disease may be induced secondary to other diseases such as hypertension, valvular heart disease, and heart failure, conferring an increased risk of stroke and sudden death. Epidemiological studies have provided evidence that genetic factors play an important role and up to 30% of clinically diagnosed patients may have a family history of atrial fibrillation. To date, several rare variants have been identified in a wide range of genes associated with ionic channels, calcium handling protein, fibrosis, conduction and inflammation. Important advances in clinical, genetic and molecular basis have been performed over the last decade, improving diagnosis and treatment. However, the genetics of atrial fibrillation is complex and pathophysiological data remains still unraveling. A better understanding of the genetic basis will induce accurate risk stratification and personalized clinical treatment. In this review, we have focused on current genetics basis of atrial fibrillation.

GENETIC ASPECTS OF AUTISM

Directory of Open Access Journals (Sweden)

Anastas LAKOSKI

1997-06-01

Full Text Available In the first paper on the syndrome of autism, Kanner described it as innate and inborn. He drew attention to the abnormalities in infancy without evidence of prior normal development and the intellectual, non emotional qualities shown by many of the parents and grandparents. Subsequently, the supposed lack of parental warmth led many clinicians to abandon the notions of constitutional deficit in the child and instead to postulate a psychogenic origin etiology was likely, genetic factors probably did not play a major role. Attention was draw to the low rate of autism in siblings, the lack of chromosome anomalies, and the similarities with syndromes associated with known brain trauma. Although the rate of autism in siblings was indeed low, it was much higher than in the general population rate providing a strong pointer to the genetic factors. The recognition that this was so, associated with the parallel finding of apparently high familiar loading for language delay, stimulated the first, systematic, twin study of autism, which suggested a strong genetic component. Subsequent research has produced findings in the same direction, although many questions remain unanswered. In this paper the evidence that has accumulated on genetic influences on autism is summarized and the remained dilemmas on this field are discussed.

Genetic genealogy reveals true Y haplogroup of House of Bourbon contradicting recent identification of the presumed remains of two French Kings.

Science.gov (United States)

Larmuseau, Maarten H D; Delorme, Philippe; Germain, Patrick; Vanderheyden, Nancy; Gilissen, Anja; Van Geystelen, Anneleen; Cassiman, Jean-Jacques; Decorte, Ronny

2014-05-01

Genetic analysis strongly increases the opportunity to identify skeletal remains or other biological samples from historical figures. However, validation of this identification is essential and should be done by DNA typing of living relatives. Based on the similarity of a limited set of Y-STRs, a blood sample and a head were recently identified as those belonging respectively to King Louis XVI and his paternal ancestor King Henry IV. Here, we collected DNA samples from three living males of the House of Bourbon to validate the since then controversial identification of these remains. The three living relatives revealed the Bourbon's Y-chromosomal variant on a high phylogenetic resolution for several members of the lineage between Henry IV and Louis XVI. This 'true' Bourbon's variant is different from the published Y-STR profiles of the blood as well as of the head. The earlier identifications of these samples can therefore not be validated. Moreover, matrilineal genealogical data revealed that the published mtDNA sequence of the head was also different from the one of a series of relatives. This therefore leads to the conclusion that the analyzed samples were not from the French kings. Our study once again demonstrated that in order to realize an accurate genetic identification of historical remains DNA typing of living persons, who are paternally or maternally related with the presumed donor of the samples, is required.

The Impact of Genetic and Non-Genetic Factors on Warfarin Dose Prediction in MENA Region: A Systematic Review.

Science.gov (United States)

Bader, Loulia Akram; Elewa, Hazem

2016-01-01

Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing. To explore the prevalence of CYP2C9 and VKORC1 variants in MENA, and the effect of these variants along with other non-genetic factors in predicting warfarin dose. In this systematic review, we included observational cross sectional and cohort studies that enrolled patients on stable warfarin dose and had the genetics and non-genetics factors associated with mean warfarin dose as the primary outcome. We searched PubMed, Medline, Scopus, PharmGKB, PHGKB, Google scholar and reference lists of relevant reviews. We identified 17 studies in eight different populations: Iranian, Israeli, Egyptian, Lebanese, Omani, Kuwaiti, Sudanese and Turkish. Most common genetic variant in all populations was the VKORC1 (-1639G>A), with a minor allele frequency ranging from 30% in Egyptians and up to 52% and 56% in Lebanese and Iranian, respectively. Variants in the CYP2C9 were less common, with the highest MAF for CYP2C9*2 among Iranians (27%). Variants in the VKORC1 and CYP2C9 were the most significant predictors of warfarin dose in all populations. Along with other genetic and non-genetic factors, they explained up to 63% of the dose variability in Omani and Israeli patients. Variants of VKORC1 and CYP2C9 are the strongest predictors of warfarin dose variability among the different populations from MENA. Although many of those populations share the same ancestry and are similar in their warfarin dose predictors, a population specific dosing algorithm is needed for the prospective estimation of warfarin

Factors associated with numbers of remaining teeth among type 2 diabetes: a cross-sectional study.

Science.gov (United States)

Huang, Jui-Chu; Peng, Yun-Shing; Fan, Jun-Yu; Jane, Sui-Whi; Tu, Liang-Tse; Chang, Chang-Cheng; Chen, Mei-Yen

2013-07-01

To explore the factors associated with the numbers of remaining teeth among type 2 diabetes community residents. Promoting oral health is an important nursing role for patients with diabetes, especially in disadvantaged areas. However, limited research has been carried out on the relationship between numbers of remaining teeth, diabetes-related biomarkers and personal oral hygiene among diabetic rural residents. A cross-sectional, descriptive design with a simple random sample was used. This study was part of a longitudinal cohort study of health promotion for preventing diabetic foot among rural community diabetic residents. It was carried out in 18 western coastal and inland districts of Chiayi County in central Taiwan. In total, 703 participants were enrolled in this study. The findings indicated that a high percentage of the participants (26%) had no remaining natural teeth. Nearly three quarters (74%) had fewer than 20 natural teeth. After controlling for the potential confounding factors, multivariate analysis demonstrated that the factors determining numbers of remaining teeth were age (p teeth were less tooth-brushing with dental floss, abnormal ankle brachial pressure and poor glycemic control. This study highlights the importance of nursing intervention in oral hygiene for patients with type 2 diabetes. It is necessary to initiate oral health promotion activities when diabetes is first diagnosed, especially for older diabetic residents of rural or coastal areas who are poorly educated. © 2013 John Wiley & Sons Ltd.

Progress in the identification of genetic factors in periodontitis

NARCIS (Netherlands)

Laine, M.L.; Jepsen, S.; Loos, B.G.

2014-01-01

The susceptibility to periodontitis is determined by a complex interplay between bacteria, the immune system, and life-style factors, and is mainly regulated by genes. The genetic factors contributing to the pathogenesis of periodontitis are still not fully defined. The aim of the present review is

Genetic factors may play a prominent role in the development of coronary heart disease dependent on important environmental factors

Science.gov (United States)

Song, C; Chang, Z; Magnusson, P K E; Ingelsson, E; Pedersen, N L

2014-01-01

Astract Song C, Chang Z, Magnusson PKE, Ingelsson E, Pedersen NL (Karolinska Institutet, Stockholm; Uppsala University, Uppsala; Sweden). Genetic factors may play a prominent role in the developmentofcoronary heart diseasedependenton important environmental factors. J InternMed2014; 275: 631–639. Objective The aim of the study was to examine whether various lifestyle factors modify genetic influences on coronary heart disease (CHD). Design The effect of lifestyle factors [including smoking, sedentary lifestyle, alcohol intake and body mass index (BMI)] on risk of CHD was evaluated via Cox regression models in a twin study of gene–environment interaction. Using structure equation modelling, we estimated genetic variance of CHD dependent on lifestyle factors. Subjects In total, 51 065 same-sex twins from 25 715 twin pairs born before 1958 and registered in the Swedish Twin Registry were eligible for this study. During the 40-year follow-up, 7264 incident CHD events were recorded. Results Smoking, sedentary lifestyle and above average BMI were significantly associated with increased CHD incidence. The heritability of CHD decreased with increasing age, as well as with increasing levels of BMI, in both men and women. Conclusions The difference in the genetic component of CHD as a function of BMI suggests that genetic factors may play a more prominent role for disease development in the absence of important environmental factors. Increased knowledge of gene–environment interactions will be important for a full understanding of the aetiology of CHD. PMID:24330166

Genetic screening of Wnt signaling factors in advanced retinopathy of prematurity

OpenAIRE

Hiraoka, Miki; Takahashi, Hiroshi; Orimo, Hideo; Hiraoka, Miina; Ogata, Tsutomu; Azuma, Noriyuki

2010-01-01

Purpose To evaluate the possibility of genetic involvement in retinopathy of prematurity (ROP). Although ROP is most often associated with low birthweight and low gestational age, these factors do not necessarily predict the severity of ROP. The possible involvement of other factors, including genetic variants, has been considered. Familial exudative vitreoretinopathy (FEVR) is a hereditary vitreoretinal disorder with clinical manifestations similar to those of ROP. Three genes involving the ...

Evaluation of some genetic factors influencing the phenotypic ...

African Journals Online (AJOL)

Evaluation of some genetic factors influencing the phenotypic severity of β thalassemia Egyptian patients. Ibtessam R Hussein, Amina M Medhat, Samir F Zohny, Alice K Abd El-Aleem, Ghada Y El-Kammah, Bardees M Foda ...

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

Experience with multiple control groups in a large population-based case-control study on genetic and environmental risk factors.

Science.gov (United States)

Pomp, E R; Van Stralen, K J; Le Cessie, S; Vandenbroucke, J P; Rosendaal, F R; Doggen, C J M

2010-07-01

We discuss the analytic and practical considerations in a large case-control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.

Generalized reduced rank latent factor regression for high dimensional tensor fields, and neuroimaging-genetic applications.

Science.gov (United States)

Tao, Chenyang; Nichols, Thomas E; Hua, Xue; Ching, Christopher R K; Rolls, Edmund T; Thompson, Paul M; Feng, Jianfeng

2017-01-01

We propose a generalized reduced rank latent factor regression model (GRRLF) for the analysis of tensor field responses and high dimensional covariates. The model is motivated by the need from imaging-genetic studies to identify genetic variants that are associated with brain imaging phenotypes, often in the form of high dimensional tensor fields. GRRLF identifies from the structure in the data the effective dimensionality of the data, and then jointly performs dimension reduction of the covariates, dynamic identification of latent factors, and nonparametric estimation of both covariate and latent response fields. After accounting for the latent and covariate effects, GRLLF performs a nonparametric test on the remaining factor of interest. GRRLF provides a better factorization of the signals compared with common solutions, and is less susceptible to overfitting because it exploits the effective dimensionality. The generality and the flexibility of GRRLF also allow various statistical models to be handled in a unified framework and solutions can be efficiently computed. Within the field of neuroimaging, it improves the sensitivity for weak signals and is a promising alternative to existing approaches. The operation of the framework is demonstrated with both synthetic datasets and a real-world neuroimaging example in which the effects of a set of genes on the structure of the brain at the voxel level were measured, and the results compared favorably with those from existing approaches. Copyright © 2016. Published by Elsevier Inc.

Genetic, Maternal, and Environmental Risk Factors for Cryptorchidism

DEFF Research Database (Denmark)

Barthold, Julia Spencer; Reinhardt, Susanne; Thorup, Jorgen

2016-01-01

genetic risk, multiple susceptibility loci, and a role for the maternal environment. Epidemiologic studies have identified low birth weight or intrauterine growth retardation as factors most strongly associated with cryptorchidism, with additional evidence suggesting that maternal smoking and gestational...

Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia

NARCIS (Netherlands)

Wouters, Mira M.; Lambrechts, Diether; Becker, Jessica; Cleynen, Isabelle; Tack, Jan; Vigo, Ana G.; Ruiz de León, Antonio; Urcelay, Elena; Pérez de la Serna, Julio; Rohof, Wout; Annese, Vito; Latiano, Anna; Palmieri, Orazio; Mattheisen, Manuel; Mueller, Michaela; Lang, Hauke; Fumagalli, Uberto; Laghi, Luigi; Zaninotto, Giovanni; Cuomo, Rosario; Sarnelli, Giovanni; Nöthen, Markus M.; Vermeire, Séverine; Knapp, Michael; Gockel, Ines; Schumacher, Johannes; Boeckxstaens, Guy E.

2014-01-01

Idiopathic achalasia is a rare motor disorder of the oesophagus characterised by neuronal loss at the lower oesophageal sphincter. Achalasia is generally accepted as a multifactorial disorder with various genetic and environmental factors being risk-associated. Since genetic factors predisposing to

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.

Genetic factors associated with small for gestational age birth and the use of human growth hormone in treating the disorder

Directory of Open Access Journals (Sweden)

Saenger Paul

2012-05-01

Full Text Available Abstract The term small for gestational age (SGA refers to infants whose birth weights and/or lengths are at least two standard deviation (SD units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH/insulin-like growth factor (IGF-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR polymorphism. Uniparental disomy (UPD and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.

Genetic factors in exercise adoption, adherence and obesity.

Science.gov (United States)

Herring, M P; Sailors, M H; Bray, M S

2014-01-01

Physical activity and exercise play critical roles in energy balance. While many interventions targeted at increasing physical activity have demonstrated efficacy in promoting weight loss or maintenance in the short term, long term adherence to such programmes is not frequently observed. Numerous factors have been examined for their ability to predict and/or influence physical activity and exercise adherence. Although physical activity has been demonstrated to have a strong genetic component in both animals and humans, few studies have examined the association between genetic variation and exercise adherence. In this review, we provide a detailed overview of the non-genetic and genetic predictors of physical activity and adherence to exercise. In addition, we report the results of analysis of 26 single nucleotide polymorphisms in six candidate genes examined for association to exercise adherence, duration, intensity and total exercise dose in young adults from the Training Interventions and Genetics of Exercise Response (TIGER) Study. Based on both animal and human research, neural signalling and pleasure/reward systems in the brain may drive in large part the propensity to be physically active and to adhere to an exercise programme. Adherence/compliance research in other fields may inform future investigation of the genetics of exercise adherence. © 2013 The Authors. obesity reviews © 2013 International Association for the Study of Obesity.

[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.

Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors

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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.

Importance of genetic factors in the etiology of atopic dermatitis: a twin study

DEFF Research Database (Denmark)

Thomsen, Simon F; Ulrik, Charlotte S; Kyvik, Kirsten O

2007-01-01

The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who wer...... dermatitis both in male and female patients (p = 0.98). The estimates were adjusted for age. The susceptibility to develop atopic dermatitis is attributable to mainly genetic differences between people. However, differences in environmental exposures also are of importance......The susceptibility to develop atopic dermatitis can be attributed both to genetic and environmental causes. We estimated the relative impact of genetic and environmental factors in the etiology of atopic dermatitis in a population-based sample of twins. From the birth cohorts of 1953-1982 who were...... with a threefold increased risk among cotwins of an affected fraternal twin, relative to the general population. Genes accounted for 82% and nonshared environmental factors accounted for 18% of the individual susceptibility to develop atopic dermatitis. The same genes contributed to the susceptibility to atopic...

Genetic factors affecting statin concentrations and subsequent myopathy: a HuGENet systematic review

Science.gov (United States)

Canestaro, William J.; Austin, Melissa A.; Thummel, Kenneth E.

2015-01-01

Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors, have proven efficacy in both lowering low-density-lipoprotein levels and preventing major coronary events, making them one of the most commonly prescribed drugs in the United States. Statins exhibit a class-wide side effect of muscle toxicity and weakness, which has led regulators to impose both dosage limitations and a recall. This review focuses on the best-characterized genetic factors associated with increased statin muscle concentrations, including the genes encoding cytochrome P450 enzymes (CYP2D6, CYP3A4, and CYP3A5), a mitochondrial enzyme (GATM), an influx transporter (SLCO1B1), and efflux transporters (ABCB1 and ABCG2). A systematic literature review was conducted to identify relevant research evaluating the significance of genetic variants predictive of altered statin concentrations and subsequent statin-related myopathy. Studies eligible for inclusion must have incorporated genotype information and must have associated it with some measure of myopathy, either creatine kinase levels or self-reported muscle aches and pains. After an initial review, focus was placed on seven genes that were adequately characterized to provide a substantive review: CYP2D6, CYP3A4, CYP3A5, GATM, SLCO1B1, ABCB1, and ABCG2. All statins were included in this review. Among the genetic factors evaluated, statin-related myopathy appears to be most strongly associated with variants in SLCO1B1. PMID:24810685

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.

A review of genetic factors contributing to the etiopathogenesis of anorectal malformations.

Science.gov (United States)

Khanna, Kashish; Sharma, Shilpa; Pabalan, Noel; Singh, Neetu; Gupta, D K

2018-01-01

Anorectal malformation (ARM) is a common congenital anomaly with a wide clinical spectrum. Recently, many genetic and molecular studies have been conducted worldwide highlighting the contribution of genetic factors in its etiology. We summarize the current literature on such genetic factors. Literature search was done using different combinations of terms related to genetics in anorectal malformations. From 2012 to June 2017, articles published in the English literature and studies conducted on human population were included. A paradigm shift was observed from the earlier studies concentrating on genetic aberrations in specific pathways to genome wide arrays exploring single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in ARM patients. Rare CNVs (including 79 genes) and SNPs have been found to genetically contribute to ARM. Out of disrupted 79 genes one such putative gene is DKK4. Down regulation of CDX-1 gene has also been implicated in isolated ARM patients. In syndromic ARM de novo microdeletion at 17q12 and a few others have been identified. Major genetic aberrations proposed in the pathogenesis of ARM affect members of the Wnt, Hox (homebox) genes, Sonic hedgehog (Shh) and Gli2, Bmp4, Fgf and CDX1 signalling pathways; probable targets of future molecular gene therapy.

Adaptive Test Selection for Factorization-based Surrogate Fitness in Genetic Programming

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Krawiec Krzysztof

2017-12-01

Full Text Available Genetic programming (GP is a variant of evolutionary algorithm where the entities undergoing simulated evolution are computer programs. A fitness function in GP is usually based on a set of tests, each of which defines the desired output a correct program should return for an exemplary input. The outcomes of interactions between programs and tests in GP can be represented as an interaction matrix, with rows corresponding to programs in the current population and columns corresponding to tests. In previous work, we proposed SFIMX, a method that performs only a fraction of interactions and employs non-negative matrix factorization to estimate the outcomes of remaining ones, shortening GP’s runtime. In this paper, we build upon that work and propose three extensions of SFIMX, in which the subset of tests drawn to perform interactions is selected with respect to test difficulty. The conducted experiment indicates that the proposed extensions surpass the original SFIMX on a suite of discrete GP benchmarks.

Resiliency to Victimization: The Role of Genetic Factors

Science.gov (United States)

Beaver, Kevin M.; Mancini, Christina; DeLisi, Matt; Vaughn, Michael G.

2011-01-01

There is a burgeoning line of criminological research examining the genetic underpinnings to a wide array of antisocial phenotypes. From this perspective, genes are typically viewed as risk factors that increase the odds of various maladaptive behaviors. However, genes can also have protective effects that insulate against the deleterious effects…

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 ...

Genetic Variants in Transcription Factors Are Associated With the Pharmacokinetics and Pharmacodynamics of Metformin

Science.gov (United States)

Goswami, S; Yee, SW; Stocker, S; Mosley, JD; Kubo, M; Castro, R; Mefford, JA; Wen, C; Liang, X; Witte, J; Brett, C; Maeda, S; Simpson, MD; Hedderson, MM; Davis, RL; Roden, DM; Giacomini, KM; Savic, RM

2014-01-01

One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic variants in transcription factors on metformin pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P < 0.01) and metformin secretory clearance (P < 0.05). Population pharmacokinetic modeling further confirmed a 24% reduction in apparent clearance in homozygous carriers of one such variant, rs784888. Genetic variants in other transcription factors, peroxisome proliferator–activated receptor-α and hepatocyte nuclear factor 4-α, were significantly associated with HbA1c change only. Overall, our study highlights the importance of genetic variants in transcription factors as modulators of metformin PK and response. PMID:24853734

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.

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

BELFAST nonagenarians: nature or nurture? Immunological, cardiovascular and genetic factors

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Rea I M

2010-05-01

Full Text Available Abstract Nonagenarians are the fastest growing sector of populations across Western European and the developed world. They are some of the oldest members of our societies and survivors of their generation and may help us understand how to age not only longer, but better. The Belfast Longevity Group enlisted the help of 500 community-living, mobile, mentally competent, 'elite' nonagenarians, as part of an ongoing study of ageing. We assessed some immunological, cardiovascular, nutritional and genetic factors and some aspects of their interaction in this group of 'oldest old'. Here we present some of the evidence related to genetic and nutritional factors which seem to be important for good quality ageing in nonagenarians from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST.

Genetic and environmental factors influencing the Placental Growth Factor (PGF) variation in two populations

DEFF Research Database (Denmark)

Sorice, Rossella; Ruggiero, Daniela; Nutile, Teresa

2012-01-01

. 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......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...

Genetics and biochemistry remain essential in the structural era of the spliceosome.

Science.gov (United States)

Mayerle, Megan; Guthrie, Christine

2017-08-01

The spliceosome is not a single macromolecular machine. Rather it is a collection of dynamic heterogeneous subcomplexes that rapidly interconvert throughout the course of a typical splicing cycle. Because of this, for many years the only high resolution structures of the spliceosome available were of smaller, isolated protein or RNA components. Consequently much of our current understanding of the spliceosome derives from biochemical and genetic techniques. Now with the publication of multiple, high resolution structures of the spliceosome, some question the relevance of traditional biochemical and genetic techniques to the splicing field. We argue such techniques are not only relevant, but vital for an in depth mechanistic understanding of pre-mRNA splicing. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons

Science.gov (United States)

Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.

2013-01-01

Background Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. Methods In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. Results A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9×10−4). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05–2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06–1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16–1.96), diabetes (OR = 1.66; 95% CI, 1.10–2.49), ≥1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06–1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17–2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. Conclusions In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD. PMID:23532479

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.

Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses.

Science.gov (United States)

Bertram, Lars; Tanzi, Rudolph E

2008-10-01

The genetic underpinnings of Alzheimer's disease (AD) remain largely elusive despite early successes in identifying three genes that cause early-onset familial AD (those that encode amyloid precursor protein (APP) and the presenilins (PSEN1 and PSEN2)), and one genetic risk factor for late-onset AD (the gene that encodes apolipoprotein E (APOE)). A large number of studies that aimed to help uncover the remaining disease-related loci have been published in recent decades, collectively proposing or refuting the involvement of over 500 different gene candidates. Systematic meta-analyses of these studies currently highlight more than 20 loci that have modest but significant effects on AD risk. This Review discusses the putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors.

Possible modification of Alzheimer's disease by statins in midlife: interactions with genetic and non-genetic risk factors.

Science.gov (United States)

Shinohara, Mitsuru; Sato, Naoyuki; Shimamura, Munehisa; Kurinami, Hitomi; Hamasaki, Toshimitsu; Chatterjee, Amarnath; Rakugi, Hiromi; Morishita, Ryuichi

2014-01-01

The benefits of statins, commonly prescribed for hypercholesterolemia, in treating Alzheimer's disease (AD) have not yet been fully established. A recent randomized clinical trial did not show any therapeutic effects of two statins on cognitive function in AD. Interestingly, however, the results of the Rotterdam study, one of the largest prospective cohort studies, showed reduced risk of AD in statin users. Based on the current understanding of statin actions and AD pathogenesis, it is still worth exploring whether statins can prevent AD when administered decades before the onset of AD or from midlife. This review discusses the possible beneficial effects of statins, drawn from previous clinical observations, pathogenic mechanisms, which include β-amyloid (Aβ) and tau metabolism, genetic and non-genetic risk factors (apolipoprotein E, cholesterol, sex, hypertension, and diabetes), and other clinical features (vascular dysfunction and oxidative and inflammatory stress) of AD. These findings suggest that administration of statins in midlife might prevent AD in late life by modifying genetic and non-genetic risk factors for AD. It should be clarified whether statins inhibit Aβ accumulation, tau pathological features, and brain atrophy in humans. To answer this question, a randomized controlled study using amyloid positron emission tomography (PET), tau-PET, and magnetic resonance imaging would be useful. This clinical evaluation could help us to overcome this devastating disease.

Genetic and psychosocial factors for benzodiazepine addiction. An analysis based on the results of the authors’ own research conducted in a group of benzodiazepine addicted and non-addicted individuals

Directory of Open Access Journals (Sweden)

Anna Konopka

2017-03-01

Full Text Available Purpose: In spite of the fact that the addictive potential of benzodiazepine (BDZ drugs has been known for a long time, benzodiazepine addiction remains a common problem for psychiatry to deal with. The etiology of benzodiazepine addiction is very complex. Among the risk factors, the course of the treatment, demographic status and psychological features of a patient seem to play an important role. The aim of this study was to investigate both psychological and genetic factors differentiating benzodiazepine addicts from non-addicted users.Methods: We analysed a cohort of 120 individuals treated with benzodiazepines divided into two groups: benzodiazepine addicts and non-addicted benzodiazepine users (the control group. In both groups we measured genetic polymorphisms of GABA A2 and MAOA. In both groups some psychometric measurements were performed – we investigated the level of depression, anxiety as a state and as a trait, personality features and the dominant coping style using the Beck Depression Scale, Hamilton Anxiety Scale, Five-Factor Personality Inventory NEO-FFI and the Coping Inventory for Stressful Situations [4,10,17,36,41,44].Results: There are some psychological and situational risk factors for benzodiazepine addiction such as high neuroticism, introversion and lack of the ability to release tension through interpersonal contacts, dominance of emotional coping style and high accumulation of critical life events during both childhood and adulthood. The genetic background still remains a field for further exploration.

Highly efficient DNA extraction method from skeletal remains

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Irena Zupanič Pajnič

2011-03-01

Full Text Available Background: This paper precisely describes the method of DNA extraction developed to acquire high quality DNA from the Second World War skeletal remains. The same method is also used for molecular genetic identification of unknown decomposed bodies in routine forensic casework where only bones and teeth are suitable for DNA typing. We analysed 109 bones and two teeth from WWII mass graves in Slovenia. Methods: We cleaned the bones and teeth, removed surface contaminants and ground the bones into powder, using liquid nitrogen . Prior to isolating the DNA in parallel using the BioRobot EZ1 (Qiagen, the powder was decalcified for three days. The nuclear DNA of the samples were quantified by real-time PCR method. We acquired autosomal genetic profiles and Y-chromosome haplotypes of the bones and teeth with PCR amplification of microsatellites, and mtDNA haplotypes 99. For the purpose of traceability in the event of contamination, we prepared elimination data bases including genetic profiles of the nuclear and mtDNA of all persons who have been in touch with the skeletal remains in any way. Results: We extracted up to 55 ng DNA/g of the teeth, up to 100 ng DNA/g of the femurs, up to 30 ng DNA/g of the tibias and up to 0.5 ng DNA/g of the humerus. The typing of autosomal and YSTR loci was successful in all of the teeth, in 98 % dekalof the femurs, and in 75 % to 81 % of the tibias and humerus. The typing of mtDNA was successful in all of the teeth, and in 96 % to 98 % of the bones. Conclusions: We managed to obtain nuclear DNA for successful STR typing from skeletal remains that were over 60 years old . The method of DNA extraction described here has proved to be highly efficient. We obtained 0.8 to 100 ng DNA/g of teeth or bones and complete genetic profiles of autosomal DNA, Y-STR haplotypes, and mtDNA haplotypes from only 0.5g bone and teeth samples.

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.

Demographic, genetic, and environmental factors that modify disease course.

Science.gov (United States)

Marrie, Ruth Ann

2011-05-01

As with susceptibility to disease, it is likely that multiple factors interact to influence the phenotype of multiple sclerosis and long-term disease outcomes. Such factors may include genetic factors, socioeconomic status, comorbid diseases, and health behaviors, as well as environmental exposures. An improved understanding of the influence of these factors on disease course may reap several benefits, such as improved prognostication, allowing us to tailor disease management with respect to intensity of disease-modifying therapies and changes in specific health behaviors, in the broad context of coexisting health issues. Such information can facilitate appropriately adjusted comparisons within and between populations. Elucidation of these factors will require careful study of well-characterized populations in which the roles of multiple factors are considered simultaneously. Copyright © 2011 Elsevier Inc. All rights reserved.

On the use of sibling recurrence risks to select environmental factors liable to interact with genetic risk factors. : GxE interaction and sibling recurrence risk

OpenAIRE

Kazma, Rémi; Bonaïti-Pellié, Catherine; Norris, Jill,; Génin, Emmanuelle

2010-01-01

International audience; Gene-environment interactions are likely to be involved in the susceptibility to multifactorial diseases but are difficult to detect. Available methods usually concentrate on some particular genetic and environmental factors. In this paper, we propose a new method to determine whether a given exposure is susceptible to interact with unknown genetic factors. Rather than focusing on a specific genetic factor, the degree of familial aggregation is used as a surrogate for ...

Diet, Cardiometabolic Factors and Type-2 Diabetes Mellitus: The Role of Genetics.

Science.gov (United States)

Marcadenti, Aline

2016-01-01

Type 2 diabetes mellitus (T2DM) is a highly prevalent condition and is associated with a number of metabolic risk factors such as excess of weight, impaired lipid profile and higher levels of blood pressure. As other complex diseases, it is strongly related to an environmental component such as sedentarism and unhealthy diet, and also to a genetic component. A cluster of variants (polymorphisms) in a large number of genes seem to interact with nutrients/dietary factors in modulating cardiometabolic parameters in healthy individuals. The role of total calories intake and also different kind of carbohydrates and dietary fats in worsening the excess of weight and/or metabolic profile in patients with diabetes is well known, but the extent to which genetic factors can modify these associations is not yet fully understood. Therefore, the aim of this mini-review is to discuss the interaction of genetics and diet in the T2DM setting, since both are strongly involved in the genesis and development of the disease.

Genetic and physiological factors affecting repair and mutagenesis in yeast

International Nuclear Information System (INIS)

Lemontt, J.F.

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data, and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described particularly in relation to their involvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus, are shown to also play a role in repair and mutagenesis

Genetic and physiological factors affecting repair and mutagenesis in yeast

International Nuclear Information System (INIS)

Lemontt, J.F.

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described, particularly in relation to their imvolvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus are shown to also play a role in repair and mutagenesis

Genetic and physiological factors affecting repair and mutagenesis in yeast

Energy Technology Data Exchange (ETDEWEB)

Lemontt, J F

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data, and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described particularly in relation to their involvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus, are shown to also play a role in repair and mutagenesis.

Genetic and physiological factors affecting repair and mutagenesis in yeast

Energy Technology Data Exchange (ETDEWEB)

Lemontt, J F

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described, particularly in relation to their imvolvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus are shown to also play a role in repair and mutagenesis.

Genetic, molecular and functional analyses of complement factor I deficiency

DEFF Research Database (Denmark)

Nilsson, S.C.; Trouw, L.A.; Renault, N.

2009-01-01

Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

Individual Differences in Scotopic Visual Acuity and Contrast Sensitivity: Genetic and Non-Genetic Influences.

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Alex J Bartholomew

Full Text Available Despite the large amount of variation found in the night (scotopic vision capabilities of healthy volunteers, little effort has been made to characterize this variation and factors, genetic and non-genetic, that influence it. In the largest population of healthy observers measured for scotopic visual acuity (VA and contrast sensitivity (CS to date, we quantified the effect of a range of variables on visual performance. We found that young volunteers with excellent photopic vision exhibit great variation in their scotopic VA and CS, and this variation is reliable from one testing session to the next. We additionally identified that factors such as Circadian preference, iris color, astigmatism, depression, sex and education have no significant impact on scotopic visual function. We confirmed previous work showing that the amount of time spent on the vision test influences performance and that laser eye surgery results in worse scotopic vision. We also showed a significant effect of intelligence and photopic visual performance on scotopic VA and CS, but all of these variables collectively explain <30% of the variation in scotopic vision. The wide variation seen in young healthy volunteers with excellent photopic vision, the high test-retest agreement, and the vast majority of the variation in scotopic vision remaining unexplained by obvious non-genetic factors suggests a strong genetic component. Our preliminary genome-wide association study (GWAS of 106 participants ruled out any common genetic variants of very large effect and paves the way for future, larger genetic studies of scotopic vision.

Beyond genetics. Influence of dietary factors and gut microbiota on type 1 diabetes

DEFF Research Database (Denmark)

Nielsen, Dennis Sandris; Krych, Lukasz; Buschard, Karsten

2014-01-01

Type 1 diabetes (T1D) is an autoimmune disease ultimately leading to destruction of insulin secreting β-cells in the pancreas. Genetic susceptibility plays an important role in T1D etiology, but even mono-zygotic twins only have a concordance rate of around 50%, underlining that other factors than...... purely genetic are involved in disease development. Here we review the influence of dietary and environmental factors on T1D development in humans as well as animal models. Even though data are still inconclusive, there are strong indications that gut microbiota dysbiosis plays an important role in T1D...... development and evidence from animal models suggests that gut microbiota manipulation might prove valuable in future prevention of T1D in genetically susceptible individuals....

Postictal psychosis: presymptomatic risk factors and the need for further investigation of genetics and pharmacotherapy

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Bromfield Edward B

2006-07-01

Full Text Available Abstract Background Postictal psychosis (PIP, an episode of psychosis occurring after a cluster of seizures, is common and may be associated with profound morbidity, including chronic psychosis. Symptoms are often pleomorphic, involving a range of psychotic symptoms, including hallucinations and disorders of thought. PIP is treatable and may be averted if presymptomatic risk factors are considered in susceptible patients and treatment is initiated. Case presentation In this report, we present an illustrative case of PIP. The patient, Mr. R, presented to our emergency room with delusions and disordered thought process following a cluster of seizures. He recovered after admission, sedation and treatment with antipsychotic medication. Discussion A list of presymptomatic risk factors is established based on review of current literature. Identification of such risk factors may potentially help with prophylactic treatment; however, little empirical research exists in this area and treatment guidelines are thus far largely based on expert opinion. Further, while the neurobiology of schizophrenia is advancing at a rapid pace, largely due to advances in genetics, the pathophysiology of PIP remains largely unknown. Considering the progress in schizophrenia research in the context of the clinical features of PIP and existing studies, potential neurobiological mechanisms for PIP are herein proposed, and further genetic analyses, which may help identify those susceptible, are warranted. Conclusion While PIP is an important problem that may present first to general hospital psychiatrists, as in the case presented, this topic is under-represented in the medical psychiatry literature. As discussed in this article, further research is needed to develop presymptomatic screens and treatment pathways to help prevent morbidity.

Genetic and other risk factors for suicidal ideation and the relationship with depression.

Science.gov (United States)

Dutta, R; Ball, H A; Siribaddana, S H; Sumathipala, A; Samaraweera, S; McGuffin, P; Hotopf, M

2017-10-01

There is a genetic contribution to the risk of suicide, but sparse prior research on the genetics of suicidal ideation. Active and passive suicidal ideation were assessed in a Sri Lankan population-based twin registry (n = 3906 twins) and a matched non-twin sample (n = 2016). Logistic regression models were used to examine associations with socio-demographic factors, environmental exposures and psychiatric symptoms. The heritability of suicidal ideation was assessed using structural equation modelling. The lifetime prevalence of any suicidal ideation was 13.0% (11.7-14.3%) for men; 21.8% (20.3-23.2%) for women, with no significant difference between twins and non-twins. Factors that predicted suicidal ideation included female gender, termination of marital relationship, low education level, urban residence, losing a parent whilst young, low standard of living and stressful life events in the preceding 12 months. Suicidal ideation was strongly associated with depression, but also with abnormal fatigue and alcohol and tobacco use. The best fitting structural equation model indicated a substantial contribution from genetic factors (57%; CI 47-66) and from non-shared environmental factors (43%; CI 34-53) in both men and women. In women this genetic component was largely mediated through depression, but in men there was a significant heritable component to suicidal ideation that was independent of depression. These are the first results to show a genetic contribution to suicidal ideation that is independent of depression outside of a high-income country. These phenomena may be generalizable, because previous research highlights similarities between the aetiology of mental disorders in Sri Lanka and higher-income countries.

Genetic risk factors for the posterior cortical atrophy variant of Alzheimer's disease.

Science.gov (United States)

Schott, Jonathan M; Crutch, Sebastian J; Carrasquillo, Minerva M; Uphill, James; Shakespeare, Tim J; Ryan, Natalie S; Yong, Keir X; Lehmann, Manja; Ertekin-Taner, Nilufer; Graff-Radford, Neill R; Boeve, Bradley F; Murray, Melissa E; Khan, Qurat Ul Ain; Petersen, Ronald C; Dickson, Dennis W; Knopman, David S; Rabinovici, Gil D; Miller, Bruce L; González, Aida Suárez; Gil-Néciga, Eulogio; Snowden, Julie S; Harris, Jenny; Pickering-Brown, Stuart M; Louwersheimer, Eva; van der Flier, Wiesje M; Scheltens, Philip; Pijnenburg, Yolande A; Galasko, Douglas; Sarazin, Marie; Dubois, Bruno; Magnin, Eloi; Galimberti, Daniela; Scarpini, Elio; Cappa, Stefano F; Hodges, John R; Halliday, Glenda M; Bartley, Lauren; Carrillo, Maria C; Bras, Jose T; Hardy, John; Rossor, Martin N; Collinge, John; Fox, Nick C; Mead, Simon

2016-08-01

The genetics underlying posterior cortical atrophy (PCA), typically a rare variant of Alzheimer's disease (AD), remain uncertain. We genotyped 302 PCA patients from 11 centers, calculated risk at 24 loci for AD/DLB and performed an exploratory genome-wide association study. We confirm that variation in/near APOE/TOMM40 (P = 6 × 10(-14)) alters PCA risk, but with smaller effect than for typical AD (PCA: odds ratio [OR] = 2.03, typical AD: OR = 2.83, P = .0007). We found evidence for risk in/near CR1 (P = 7 × 10(-4)), ABCA7 (P = .02) and BIN1 (P = .04). ORs at variants near INPP5D and NME8 did not overlap between PCA and typical AD. Exploratory genome-wide association studies confirmed APOE and identified three novel loci: rs76854344 near CNTNAP5 (P = 8 × 10(-10) OR = 1.9 [1.5-2.3]); rs72907046 near FAM46A (P = 1 × 10(-9) OR = 3.2 [2.1-4.9]); and rs2525776 near SEMA3C (P = 1 × 10(-8), OR = 3.3 [2.1-5.1]). We provide evidence for genetic risk factors specifically related to PCA. We identify three candidate loci that, if replicated, may provide insights into selective vulnerability and phenotypic diversity in AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

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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

Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

DEFF Research Database (Denmark)

Larsen, TB; Nørgaard-Pedersen, B; Lundemose, JB

2000-01-01

in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome...... or unknown risk factors for thrombosis as possible etiological factors for sudden infant death syndrome. It is likely that we must continuously employ the exclusion principle on possible etiological causes in genetic material from a large group of victims of sudden infant death syndrome if the phenomenon...

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...

Molecular genetic analysis of activation-tagged transcription factors thought to be involved in photomorphogenesis

Energy Technology Data Exchange (ETDEWEB)

Neff, Michael M.

2011-06-23

This is a final report for Department of Energy Grant No. DE-FG02-08ER15927 entitled “Molecular Genetic Analysis of Activation-Tagged Transcription Factors Thought to be Involved in Photomorphogenesis”. Based on our preliminary photobiological and genetic analysis of the sob1-D mutant, we hypothesized that OBP3 is a transcription factor involved in both phytochrome and cryptochrome-mediated signal transduction. In addition, we hypothesized that OBP3 is involved in auxin signaling and root development. Based on our preliminary photobiological and genetic analysis of the sob2-D mutant, we also hypothesized that a related gene, LEP, is involved in hormone signaling and seedling development.

Dissecting high-dimensional phenotypes with bayesian sparse factor analysis of genetic covariance matrices.

Science.gov (United States)

Runcie, Daniel E; Mukherjee, Sayan

2013-07-01

Quantitative genetic studies that model complex, multivariate phenotypes are important for both evolutionary prediction and artificial selection. For example, changes in gene expression can provide insight into developmental and physiological mechanisms that link genotype and phenotype. However, classical analytical techniques are poorly suited to quantitative genetic studies of gene expression where the number of traits assayed per individual can reach many thousand. Here, we derive a Bayesian genetic sparse factor model for estimating the genetic covariance matrix (G-matrix) of high-dimensional traits, such as gene expression, in a mixed-effects model. The key idea of our model is that we need consider only G-matrices that are biologically plausible. An organism's entire phenotype is the result of processes that are modular and have limited complexity. This implies that the G-matrix will be highly structured. In particular, we assume that a limited number of intermediate traits (or factors, e.g., variations in development or physiology) control the variation in the high-dimensional phenotype, and that each of these intermediate traits is sparse - affecting only a few observed traits. The advantages of this approach are twofold. First, sparse factors are interpretable and provide biological insight into mechanisms underlying the genetic architecture. Second, enforcing sparsity helps prevent sampling errors from swamping out the true signal in high-dimensional data. We demonstrate the advantages of our model on simulated data and in an analysis of a published Drosophila melanogaster gene expression data set.

Non-genetic factors affecting fertility traits in South African Holstein ...

African Journals Online (AJOL)

referee1

2014-03-08

Mar 8, 2014 ... non-genetic factors affect the fertility of dairy cows. ... (2002) found conception rates of 64% in open heifers and 39% in .... the number of days from calving date to first service date for Holstein cows in the USA increased from.

Genetic and non-iodine-related factors in the aetiology of nodular goitre

DEFF Research Database (Denmark)

Knudsen, Nils; Brix, Thomas Heiberg

2014-01-01

Genetic and a large number of environmental non-iodine-related factors play a role in the cause of nodular goitre. Most evidence for the influence of genetic and environmental factors in the cause of goitre is from cross-sectional, population-based studies. Only a few studies have included...... prospective data on risk factors for nodular goitre, although few prospective data are available on the effect of iodine and tobacco smoking on goitre development. Goitre is not one single phenotype. Many epidemiological studies do not distinguish diffuse from nodular goitre, as the investigated parameter...... is often thyroid volume or frequency with increased thyroid volume. Moreover, information on the presence and effect of gene-environment, gene-gene, and environment-environment effect modifications is limited. Thus, firm conclusions about the relative contributions and causality of the investigated risk...

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...

Characterizing the genetic influences on risk aversion.

Science.gov (United States)

Harrati, Amal

2014-01-01

Risk aversion has long been cited as an important factor in retirement decisions, investment behavior, and health. Some of the heterogeneity in individual risk tolerance is well understood, reflecting age gradients, wealth gradients, and similar effects, but much remains unexplained. This study explores genetic contributions to heterogeneity in risk aversion among older Americans. Using over 2 million genetic markers per individual from the U.S. Health and Retirement Study, I report results from a genome-wide association study (GWAS) on risk preferences using a sample of 10,455 adults. None of the single-nucleotide polymorphisms (SNPs) are found to be statistically significant determinants of risk preferences at levels stricter than 5 × 10(-8). These results suggest that risk aversion is a complex trait that is highly polygenic. The analysis leads to upper bounds on the number of genetic effects that could exceed certain thresholds of significance and still remain undetected at the current sample size. The findings suggest that the known heritability in risk aversion is likely to be driven by large numbers of genetic variants, each with a small effect size.

Estimating the relative contributions of maternal genetic, paternal genetic and intrauterine factors to offspring birth weight and head circumference.

Science.gov (United States)

Rice, Frances; Thapar, Anita

2010-07-01

Genetic factors and the prenatal environment contribute to birth weight. However, very few types of study design can disentangle their relative contribution. To examine maternal genetic and intrauterine contributions to offspring birth weight and head circumference. To compare the contribution of maternal and paternal genetic effects. Mothers and fathers were either genetically related or unrelated to their offspring who had been conceived by in vitro fertilization. 423 singleton full term offspring, of whom 262 were conceived via homologous IVF (both parents related), 66 via sperm donation (mother only related) and 95 via egg donation (father only related). Maternal weight at antenatal booking, current weight and maternal height. Paternal current weight and height were all predictors. Infant birth weight and head circumference were outcomes. Genetic relatedness was the main contributing factor between measures of parental weight and offspring birth weight as correlations were only significant when the parent was related to the child. However, there was a contribution of the intrauterine environment to the association between maternal height and both infant birth weight and infant head circumference as these were significant even when mothers were unrelated to their child. Both maternal and paternal genes made contributions to infant birth weight. Maternal height appeared to index a contribution of the intrauterine environment to infant growth and gestational age. Results suggested a possible biological interaction between the intrauterine environment and maternal inherited characteristics which suppresses the influence of paternal genes. 2010 Elsevier Ltd. All rights reserved.

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

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

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.

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

Genetic modifiers of comatose mutations in Drosophila: insights into neuronal NSF (N-ethylmaleimide-sensitive fusion factor) functions.

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Sanyal, Subhabrata; Krishnan, K S

2012-09-01

By the middle of the 20th century, development of powerful genetic approaches had ensured that the fruit fly would remain a model organism of choice for genetic and developmental studies. But in the 1970s, a few pioneering groups turned their attention to the prospect of using the fly for neurophysiological experiments. They proposed that in a poikilothermic organism such as Drosophila, temperature-sensitive or "ts" mutations in proteins that controlled nerve function would translate to a "ts" paralytic phenotype. This was by no means an obvious or even a likely assumption. However, following directed screens these groups soon reported dramatic demonstrations of reversible ts paralysis in fly mutants. Resultantly, these "simple" experiments led to the isolation of a number of conditional mutations including shibire, paralytic, and comatose. All have since been cloned and have enabled deep mechanistic insights into synaptic transmission and nerve conduction. comatose (comt) mutations, for example, were found to map to missense changes in dNSF1, a neuron-specific fly homolog of mammalian NSF (N-ethylmaleimide-sensitive fusion factor). Studies on comt were also some of the first to discriminate between nuanced models of NSF function during presynaptic transmitter release that have since been borne out by experiments in multiple preparations. Here, the authors present an overview of NSF function as it is understood today, with an emphasis on contributions from Drosophila beginning with experiments carried out by Obaid Siddiqi in the Benzer laboratory. The authors also outline initial results from a genetic screen for phenotypic modifiers of comt that hold the promise of further elucidating NSF function at the synapse. Over the years, the neuromuscular system of Drosophila has served as a uniquely accessible model to unravel mechanisms underlying synaptic transmission. To this day, ts paralysis remains one of the most emphatic demonstrations of nerve function in an

Genetic and environmental factors interact to influence anxiety.

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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.

Lobular breast cancer: incidence and genetic and non-genetic risk factors.

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Dossus, Laure; Benusiglio, Patrick R

2015-03-13

While most invasive breast cancers consist of carcinomas of the ductal type, about 10% are invasive lobular carcinomas. Invasive lobular and ductal carcinomas differ with respect to risk factors. Invasive lobular carcinoma is more strongly associated with exposure to female hormones, and therefore its incidence is more subject to variation. This is illustrated by US figures during the 1987 to 2004 period: after 12 years of increases, breast cancer incidence declined steadily from 1999 to 2004, reflecting among other causes the decreasing use of menopausal hormone therapy, and these variations were stronger for invasive lobular than for invasive ductal carcinoma. Similarly, invasive lobular carcinoma is more strongly associated with early menarche, late menopause and late age at first birth. As for genetic risk factors, four high-penetrance genes are tested in clinical practice when genetic susceptibility to breast cancer is suspected, BRCA1, BRCA2, TP53 and CDH1. Germline mutations in BRCA1 and TP53 are predominantly associated with invasive ductal carcinoma, while BRCA2 mutations are associated with both ductal and lobular cancers. CDH1, the gene coding for the E-cadherin adhesion protein, is of special interest as mutations are associated with invasive lobular carcinoma, but never with ductal carcinoma. It was initially known as the main susceptibility gene for gastric cancer of the diffuse type, but the excess of breast cancers of the lobular type in CDH1 families led researchers to identify it also as a susceptibility gene for invasive lobular carcinoma. The risk of invasive lobular carcinoma is high in female mutation carriers, as about 50% are expected to develop the disease. Carriers must therefore undergo intensive breast cancer screening, with, for example, yearly magnetic resonance imaging and mammogram starting at age 30 years.

How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis.

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Deth, Richard; Muratore, Christina; Benzecry, Jorge; Power-Charnitsky, Verna-Ann; Waly, Mostafa

2008-01-01

Recently higher rates of autism diagnosis suggest involvement of environmental factors in causing this developmental disorder, in concert with genetic risk factors. Autistic children exhibit evidence of oxidative stress and impaired methylation, which may reflect effects of toxic exposure on sulfur metabolism. We review the metabolic relationship between oxidative stress and methylation, with particular emphasis on adaptive responses that limit activity of cobalamin and folate-dependent methionine synthase. Methionine synthase activity is required for dopamine-stimulated phospholipid methylation, a unique membrane-delimited signaling process mediated by the D4 dopamine receptor that promotes neuronal synchronization and attention, and synchrony is impaired in autism. Genetic polymorphisms adversely affecting sulfur metabolism, methylation, detoxification, dopamine signaling and the formation of neuronal networks occur more frequently in autistic subjects. On the basis of these observations, a "redox/methylation hypothesis of autism" is described, in which oxidative stress, initiated by environment factors in genetically vulnerable individuals, leads to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks.

Environmental and genetic factors influence the vitamin D content of cows' milk.

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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.

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...

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

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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.

Effect of breed and non-genetic factors on percentage milk ...

African Journals Online (AJOL)

This study was done to determine the effect of breed and non-genetic factors on percentage milk composition of smallholders' dual-purpose cattle on-farm in the Ashanti Region. Fresh milk samples from various breeds of cows were assessed for percentage components of protein, fat, lactose, cholesterol, solidnon- fat and ...

Genetic analysis of cardiovascular risk factor clustering in spontaneous hypertension

Czech Academy of Sciences Publication Activity Database

Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Kostka, Vlastimil; Musilová, Alena; Kazdová, L.; Fučíková, A.; Křenová, D.; Bílá, V.; Křen, Vladimír

2000-01-01

Roč. 46, - (2000), s. 233-240 ISSN 0015-5497 R&D Projects: GA MŠk LN00A079; GA ČR GA305/00/1646; GA ČR GA301/00/1636; GA MZd NB4904 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.667, year: 2000

Anorexia nervosa and major depression: shared genetic and environmental risk factors.

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Wade, T D; Bulik, C M; Neale, M; Kendler, K S

2000-03-01

The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%-84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.

Common Genetic and Nonshared Environmental Factors Contribute to the Association between Socioemotional Dispositions and the Externalizing Factor in Children

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Taylor, Jeanette; Allan, Nicholas; Mikolajewski, Amy J.; Hart, Sara A.

2013-01-01

Background: Childhood behavioral disorders including conduct disorder (CD), oppositional defiant disorder (ODD), and attention-deficit/hyperactivity disorder (ADHD) often co-occur. Prior twin research shows that common sets of genetic and environmental factors are associated with these various disorders and they form a latent factor called…

Unstructured Socializing with Peers and Delinquent Behavior: A Genetically Informed Analysis.

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Meldrum, Ryan C; Barnes, J C

2017-09-01

A large body of research finds that unstructured socializing with peers is positively associated with delinquency during adolescence. Yet, existing research has not ruled out the potential for confounding due to genetic factors and factors that can be traced to environments shared between siblings. To fill this void, the current study examines whether the association between unstructured socializing with peers and delinquent behavior remains when accounting for genetic factors, shared environmental influences, and a variety of non-shared environmental covariates. We do so by using data from the twin subsample of the National Longitudinal Study of Adolescent to Adult Health (n = 1200 at wave 1 and 1103 at wave 2; 51% male; mean age at wave 1 = 15.63). Results from both cross-sectional and lagged models indicate the association between unstructured socializing with peers and delinquent behavior remains when controlling for both genetic and environmental influences. Supplementary analyses examining the association under different specifications offer additional, albeit qualified, evidence supportive of this finding. The study concludes with a discussion highlighting the importance of limiting free time with friends in the absence of authority figures as a strategy for reducing delinquency during adolescence.

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

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

NARCIS (Netherlands)

Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P; Li, Xiuhong; Kingsley, Lawrence A; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; De Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; De Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A; Reiss, Peter; Weber, Rainer; Bucher, Heiner C; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E; Schölvinck, Elisabeth H.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the

Exploring Genetic Factors Involved in Huntington Disease Age of Onset

DEFF Research Database (Denmark)

Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel

2015-01-01

age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample......Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim...... of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms...

Genetic structure of personality factors and bipolar disorder in families segregating bipolar disorder.

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Hare, Elizabeth; Contreras, Javier; Raventos, Henriette; Flores, Deborah; Jerez, Alvaro; Nicolini, Humberto; Ontiveros, Alfonso; Almasy, Laura; Escamilla, Michael

2012-02-01

Bipolar disorder (BPD) has been associated with variations in personality dimensions, but the nature of this relationship has been unclear. In this study, the heritabilities of BPD and the Big Five personality factors and the genetic correlations between BPD and personality factors are reported. The participants in this study were 1073 individuals from 172 families of Mexican or Central American ancestry. Heritabilities and genetic correlations were calculated under a polygenic model using the maximum-likelihood method of obtaining variance components implemented in the SOLAR software package. Heritabilities of 0.49, 0.43, and 0.43 were found for the narrowest phenotype (schizoaffective bipolar and bipolar I), the intermediate phenotype (schizoaffective bipolar, bipolar I, and bipolar II), and the broadest phenotype (schizoaffective bipolar, bipolar I, bipolar II, and recurrent depression), respectively. For the Big Five personality factors, heritabilities were 0.25 for agreeableness, 0.24 for conscientiousness, 0.24 for extraversion, 0.23 for neuroticism, and 0.32 for openness to experience. For the narrowest phenotype, a significant negative correlation (-0.32) with extraversion was found. For the broadest phenotype, negative correlations were found for agreeableness (-0.35), conscientiousness (-0.39), and extraversion (-0.44). A positive correlation (0.37) was found with neuroticism. It is not possible to determine whether aspects of personality are factors in the development of bipolar disorder or vice versa. The short form of the NEO does not provide the ability to examine in detail which facets of extraversion are most closely related to bipolar disorder or to compare our results with studies that have used the long version of the scale. This study establishes a partial genetic basis for the Big Five personality factors in this set of families, while the environmental variances demonstrate that non-genetic factors are also important in their influence on

Genetic Control of Seed Shattering in Rice by the APETALA2 Transcription Factor SHATTERING ABORTION1[C][W][OA

Science.gov (United States)

Zhou, Yan; Lu, Danfeng; Li, Canyang; Luo, Jianghong; Zhu, Bo-Feng; Zhu, Jingjie; Shangguan, Yingying; Wang, Zixuan; Sang, Tao; Zhou, Bo; Han, Bin

2012-01-01

Seed shattering is an important agricultural trait in crop domestication. SH4 (for grain shattering quantitative trait locus on chromosome 4) and qSH1 (for quantitative trait locus of seed shattering on chromosome 1) genes have been identified as required for reduced seed shattering during rice (Oryza sativa) domestication. However, the regulatory pathways of seed shattering in rice remain unknown. Here, we identified a seed shattering abortion1 (shat1) mutant in a wild rice introgression line. The SHAT1 gene, which encodes an APETALA2 transcription factor, is required for seed shattering through specifying abscission zone (AZ) development in rice. Genetic analyses revealed that the expression of SHAT1 in AZ was positively regulated by the trihelix transcription factor SH4. We also identified a frameshift mutant of SH4 that completely eliminated AZs and showed nonshattering. Our results suggest a genetic model in which the persistent and concentrated expression of active SHAT1 and SH4 in the AZ during early spikelet developmental stages is required for conferring AZ identification. qSH1 functioned downstream of SHAT1 and SH4, through maintaining SHAT1 and SH4 expression in AZ, thus promoting AZ differentiation. PMID:22408071

Optimization of Q-factor of AFM cantilevers using genetic algorithms

Energy Technology Data Exchange (ETDEWEB)

Perez-Cruz, Angel, E-mail: elapc27@gmail.com [Faculty of Engineering, Universidad Autonoma de Queretaro, Queretaro (Mexico); Dominguez-Gonzalez, Aurelio [Faculty of Engineering, Universidad Autonoma de Queretaro, Queretaro (Mexico); Stiharu, Ion [Department of Mechanical and Industrial Engineering, Concordia University, Montreal (Canada); Osornio-Rios, Roque A. [Faculty of Engineering, Universidad Autonoma de Queretaro, Queretaro (Mexico)

2012-04-15

Micro cantilever beams have been intensively used in sensing applications including to scanning profiles and surfaces where there resolution and imaging speed are critical. Force resolution is related to the Q-factor. When the micro-cantilever operates in air with small separation gaps, the Q-factor is even more reduced due to the squeeze-film damping effect. Thus, the optimization of the configuration of an AFM micro-cantilever is presented in this work with the objective of improving its Q-factor. To accomplish this task, we propose the inclusion of holes as breathing chimneys in the initial design to reduce the squeeze-film damping effect. The evaluation of the Q-factor was carried out using finite element model, which is implemented to work together with the squeeze-film damping model. The methodology applied in the optimization process was genetic algorithms, which considers as constraints the maximum allowable stress, fundamental frequency and spring constant with respect to the initial design. The results show that the optimum design, which includes holes with an optimal location, increases the Q-factor almost five times compared to the initial design. -- Highlights: Black-Right-Pointing-Pointer It was optimized the Q-factor of a cantilever, which operates near to the surface in air. Black-Right-Pointing-Pointer It was proposed the inclusion of holes as breathing chimneys in the cantilever's surface. Black-Right-Pointing-Pointer Genetic algorithms and finite element analysis were applied to find the optimum configuration for the Q-factor. Black-Right-Pointing-Pointer Optimum design keeps first frequency and the spring constant very close to the original and has a better force resolution. Black-Right-Pointing-Pointer Final design can be easily manufactured through a mask.

Probability Model of Allele Frequency of Alzheimer’s Disease Genetic Risk Factor

Directory of Open Access Journals (Sweden)

Afshin Fayyaz-Movaghar

2016-06-01

Full Text Available Background and Purpose: The identification of genetics risk factors of human diseases is very important. This study is conducted to model the allele frequencies (AFs of Alzheimer’s disease. Materials and Methods: In this study, several candidate probability distributions are fitted on a data set of Alzheimer’s disease genetic risk factor. Unknown parameters of the considered distributions are estimated, and some criterions of goodness-of-fit are calculated for the sake of comparison. Results: Based on some statistical criterions, the beta distribution gives the best fit on AFs. However, the estimate values of the parameters of beta distribution lead us to the standard uniform distribution. Conclusion: The AFs of Alzheimer’s disease follow the standard uniform distribution.

Genetic predictors of obesity development

Directory of Open Access Journals (Sweden)

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.

Genetic Variations Involved in Vitamin E Status

Directory of Open Access Journals (Sweden)

Patrick Borel

2016-12-01

Full Text Available Vitamin E (VE is the generic term for four tocopherols and four tocotrienols that exhibit the biological activity of α-tocopherol. VE status, which is usually estimated by measuring fasting blood VE concentration, is affected by numerous factors, such as dietary VE intake, VE absorption efficiency, and VE catabolism. Several of these factors are in turn modulated by genetic variations in genes encoding proteins involved in these factors. To identify these genetic variations, two strategies have been used: genome-wide association studies and candidate gene association studies. Each of these strategies has its advantages and its drawbacks, nevertheless they have allowed us to identify a list of single nucleotide polymorphisms associated with fasting blood VE concentration and α-tocopherol bioavailability. However, much work remains to be done to identify, and to replicate in different populations, all the single nucleotide polymorphisms involved, to assess the possible involvement of other kind of genetic variations, e.g., copy number variants and epigenetic modifications, in order to establish a reliable list of genetic variations that will allow us to predict the VE status of an individual by knowing their genotype in these genetic variations. Yet, the potential usefulness of this area of research is exciting with regard to personalized nutrition and for future clinical trials dedicated to assessing the biological effects of the various isoforms of VE.

Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.

Science.gov (United States)

Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y

2017-05-01

Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P < .0001). The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

NARCIS (Netherlands)

Rotger, Margalida; Glass, Tracy R.; Junier, Thomas; Lundgren, Jens; Neaton, James D.; Poloni, Estella S.; van 't Wout, Angélique B.; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F.; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle; Gras, Luuk A.; Schuitemaker, Hanneke; Albini, Laura; Torti, Carlo; Jacobson, Lisa P.; Li, Xiuhong; Kingsley, Lawrence A.; Carli, Federica; Guaraldi, Giovanni; Ford, Emily S.; Sereti, Irini; Hadigan, Colleen; Martinez, Esteban; Arnedo, Mireia; Egaña-Gorroño, Lander; Gatell, Jose M.; Law, Matthew; Bendall, Courtney; Petoumenos, Kathy; Rockstroh, Jürgen; Wasmuth, Jan-Christian; Kabamba, Kabeya; Delforge, Marc; de Wit, Stephane; Berger, Florian; Mauss, Stefan; de Paz Sierra, Mariana; Losso, Marcelo; Belloso, Waldo H.; Leyes, Maria; Campins, Antoni; Mondi, Annalisa; de Luca, Andrea; Bernardino, Ignacio; Barriuso-Iglesias, Mónica; Torrecilla-Rodriguez, Ana; Gonzalez-Garcia, Juan; Arribas, José R.; Fanti, Iuri; Gel, Silvia; Puig, Jordi; Negredo, Eugenia; Gutierrez, Mar; Domingo, Pere; Fischer, Julia; Fätkenheuer, Gerd; Alonso-Villaverde, Carlos; Macken, Alan; Woo, James; McGinty, Tara; Mallon, Patrick; Mangili, Alexandra; Skinner, Sally; Wanke, Christine A.; Reiss, Peter; Weber, Rainer; Bucher, Heiner C.; Fellay, Jacques; Telenti, Amalio; Tarr, Philip E.; Gras, A. Luuk; van Wout, Angelique B.; Arnedo-Valero, Mireia; Sierra, Mariana de Paz; Rodriguez, Ana Torrecilla; Garcia, Juan Gonzalez; Arribas, Jose R.; Aubert, V.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Francioli, P.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirsch, H. H.; Hirschel, B.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Prins, Yerly S. J. M.; Kuijpers, T. W.; Scherpbier, H. J.; Boer, K.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Vrouenraets, S. M. E.; Pajkrt, D.; Bos, J. C.; van der Valk, M.; Schreij, G.; Lowe, S.; Oude Lashof, A.; Pronk, M. J. H.; Bravenboer, B.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; van der Feltz, M.; Nouwen, J. L.; Gelinck, L. B. S.; Verbon, A.; Rijnders, B. J. A.; van de Ven-de Ruiter, E. D.; Slobbe, L.; Haag, Den; Kauffmann, R. H.; Schippers, E. F.; Groeneveld, P. H. P.; Alleman, M. A.; Bouwhuis, J. W.; ten Kate, R. W.; Soetekouw, R.; Kroon, F. P.; van den Broek, P. J.; van Dissel, J. T.; Arend, S. M.; van Nieuwkoop, C.; de Boer, M. J. G.; Jolink, H.; den Hollander, J. G.; Pogany, K.; Bronsveld, W.; Kortmann, W.; van Twillert, G.; van Houte, D. P. F.; Polée, M. B.; van Vonderen, M. G. A.; ten Napel, C. H. H.; Kootstra, G. J.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; van den Berk, G. E. L.; Juttmann, J. R.; van Kasteren, M. E. E.; Brouwer, A. E.; Mulder, J. W.; van Gorp, E. C. M.; Smit, P. M.; Weijer, S.; van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; van Assen, S.; Stek, C. J.; Hoepelman, I. M.; Mudrikova, T.; Schneider, M. M. E.; Jaspers, C. A. J. J.; Ellerbroek, P. M.; Peters, E. J. G.; Maarschalk-Ellerbroek, L. J.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; van der Hilst, J. C. H.; Richter, C.; van der Berg, J. P.; Gisolf, E. H.; Margolick, Joseph B.; Plankey, Michael; Crain, Barbara; Dobs, Adrian; Farzadegan, Homayoon; Gallant, Joel; Johnson-Hill, Lisette; Sacktor, Ned; Selnes, Ola; Shepard, James; Thio, Chloe; Phair, John P.; Wolinsky, Steven M.; Badri, Sheila; Conover, Craig; O'Gorman, Maurice; Ostrow, David; Palella, Frank; Ragin, Ann; Detels, Roger; Martínez-Maza, Otoniel; Aronow, Aaron; Bolan, Robert; Breen, Elizabeth; Butch, Anthony; Fahey, John; Jamieson, Beth; Miller, Eric N.; Oishi, John; Vinters, Harry; Visscher, Barbara R.; Wiley, Dorothy; Witt, Mallory; Yang, Otto; Young, Stephen; Zhang, Zuo Feng; Rinaldo, Charles R.; Becker, James T.; Cranston, Ross D.; Martinson, Jeremy J.; Mellors, John W.; Silvestre, Anthony J.; Stall, Ronald D.; Muñoz, Alvaro; Abraham, Alison; Althoff, Keri; Cox, Christopher; D'Souza, Gypsyamber; Gange, Stephen J.; Golub, Elizabeth; Schollenberger, Janet; Seaberg, Eric C.; Su, Sol; Huebner, Robin E.; Dominguez, Geraldina; Moroni, M.; Angarano, G.; Antinori, A.; Carosi, G.; Cauda, R.; Monforte, A. d'Arminio; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Sagnelli, E.; Viale, P. L.; Von Schlosser, F.; d'Arminio Monforte, A.; Ammassari, A.; Andreoni, M.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; de Luca, A.; Gargiulo, M.; Gervasoni, C.; Girardi, E.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Murri, R.; Mussini, C.; Puoti, M.; Torti, C.; Fanti, I.; Formenti, T.; Galli, Laura; Lorenzini, Patrizia; Montroni, M.; Giacometti, A.; Costantini, A.; Riva, A.; Tirelli, U.; Martellotta, F.; Ladisa, N.; Lazzari, G.; Verucchi, G.; Castelli, F.; Scalzini, A.; Minardi, C.; Bertelli, D.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Carnevale, G.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Leoncini, F.; Mazzotta, F.; Pozzi, M.; Cassola, G.; Viscoli, G.; Viscoli, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, P.; Rizzardini, G.; Ridolfo, A. L.; Foschi, A.; Salpietro, S.; Galli, A.; Bigoloni, A.; Spagnuolo, V.; Merli, S.; Carenzi, L.; Moioli, M. C.; Cicconi, P.; Bisio, L.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; de Marco, M.; Ferrari, C.; Borghi, R.; Baldelli, F.; Belfiori, B.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Narciso, P.; Tozzi, V.; Vullo, V.; d'Avino, A.; Zaccarelli, M.; Gallo, L.; Acinapura, R.; Capozzi, M.; Libertone, R.; Trotta, M. P.; Tebano, G.; Cattelan, A. M.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Raise, N. N.; Ebo, F.; Pellizzer, G.; Manfrin, V.; Law, M.; Petoumenos, K.; McManus, H.; Wright, S.; Bendall, C.; Moore, R.; Edwards, S.

2013-01-01

Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV

Association of education & lifestyle factors with the perception of genetic knowledge on the development of lung cancer

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Liang Wang

2016-01-01

Full Text Available Background & objectives: The perception of genetic knowledge is useful for improving the heath behaviour change against developing cancers. However, no studies have investigated the perception of genetic knowledge on the development of lung cancer. The aim of this study was to examine demographic and lifestyle factors of the perception of genetic knowledge on the development of lung cancer. Methods: Data on 2,295 US adults (739 had the perception of genetic knowledge were taken from the 2003 Health Information National Trends Survey. Multiple logistic regression models were used to evaluate potential factors of the perception of genetic knowledge of lung cancer. Results: Participants aged ≥65 yr were more likely to have the perception of genetic knowledge than those aged 18-44 yr (OR=1.77, 95% CI=1.27-2.46. Higher education was associated with a greater perception of genetic knowledge (OR=1.47, 95% CI=1.16-1.87. Subjects with correct smoking attitude were more than three times more likely to have the perception of genetic knowledge (OR=3.15, 95% CI=2.10-4.72. Subjects with exercise were at an increased likelihood of having the perception of genetic knowledge than those without exercise (OR=1.63, 95% CI=1.24-2.13. Interpretation & conclusions: Positive associations were observed between education and lifestyle factors and the perception of genetic knowledge on the development of lung cancer among US adults. Strategies developed to improve the perception of genetic knowledge of lung cancer may target on individuals who are young, less educated, and lack correct smoking attitude or exercise.

Genetics of bipolar disorder

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Kerner B

2014-02-01

Full Text Available Berit Kerner Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA Abstract: Bipolar disorder is a common, complex genetic disorder, but the mode of transmission remains to be discovered. Many researchers assume that common genomic variants carry some risk for manifesting the disease. The research community has celebrated the first genome-wide significant associations between common single nucleotide polymorphisms (SNPs and bipolar disorder. Currently, attempts are under way to translate these findings into clinical practice, genetic counseling, and predictive testing. However, some experts remain cautious. After all, common variants explain only a very small percentage of the genetic risk, and functional consequences of the discovered SNPs are inconclusive. Furthermore, the associated SNPs are not disease specific, and the majority of individuals with a “risk” allele are healthy. On the other hand, population-based genome-wide studies in psychiatric disorders have rediscovered rare structural variants and mutations in genes, which were previously known to cause genetic syndromes and monogenic Mendelian disorders. In many Mendelian syndromes, psychiatric symptoms are prevalent. Although these conditions do not fit the classic description of any specific psychiatric disorder, they often show nonspecific psychiatric symptoms that cross diagnostic boundaries, including intellectual disability, behavioral abnormalities, mood disorders, anxiety disorders, attention deficit, impulse control deficit, and psychosis. Although testing for chromosomal disorders and monogenic Mendelian disorders is well established, testing for common variants is still controversial. The standard concept of genetic testing includes at least three broad criteria that need to be fulfilled before new genetic tests should be introduced: analytical validity, clinical validity, and clinical utility. These criteria are

[Genetics of ischemic stroke].

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Gschwendtner, A; Dichgans, M

2013-02-01

Stroke is one of the most widespread causes of mortality und disability worldwide. Around 80 % of strokes are ischemic and different forms of intracranial bleeding account for the remaining cases. Monogenic stroke disorders are rare but the diagnosis may lead to specific therapeutic consequences for the affected patients who are predominantly young. In common sporadic stroke, genetic factors play a role in the form of susceptibility genes. Their discovery may give rise to new therapeutic options in the future.

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study

International Nuclear Information System (INIS)

Celeng, Csilla; Kolossvary, Marton; Kovacs, Attila; Molnar, Andrea Agnes; Szilveszter, Balint; Karolyi, Mihaly; Jermendy, Adam L.; Karady, Julia; Merkely, Bela; Maurovich-Horvat, Pal; Horvath, Tamas; Tarnoki, Adam D.; Tarnoki, David L.; Voros, Szilard; Jermendy, Gyoergy

2017-01-01

Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. (orig.)

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study

Energy Technology Data Exchange (ETDEWEB)

Celeng, Csilla; Kolossvary, Marton; Kovacs, Attila; Molnar, Andrea Agnes; Szilveszter, Balint; Karolyi, Mihaly; Jermendy, Adam L.; Karady, Julia; Merkely, Bela; Maurovich-Horvat, Pal [Semmelweis University, MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Budapest (Hungary); Horvath, Tamas [Budapest University of Technology and Economics, Department of Hydrodynamic Systems, Budapest (Hungary); Tarnoki, Adam D.; Tarnoki, David L. [Semmelweis University, Department of Radiology and Oncotherapy, Budapest (Hungary); Voros, Szilard [Global Genomics Group, Atlanta, GA (United States); Jermendy, Gyoergy [Bajcsy-Zsilinszky Hospital, Medical Department, Budapest (Hungary)

2017-06-15

Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. (orig.)

Incorporating latitudinal and central–marginal trends in assessing genetic variation across species ranges

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Qinfeng Guo

2012-01-01

The genetic variation across a species’ range is an important factor in speciation and conservation, yet searching for general patterns and underlying causes remains challenging. While the majority of comparisons between central and marginal populations have revealed a general central–marginal (C-M) decline in genetic diversity, others show no clear pattern. Similarly...

Duplex Alu Screening for Degraded DNA of Skeletal Human Remains

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Fabian Haß

2017-10-01

Full Text Available The human-specific Alu elements, belonging to the class of Short INterspersed Elements (SINEs, have been shown to be a powerful tool for population genetic studies. An earlier study in this department showed that it was possible to analyze Alu presence/absence in 3000-year-old skeletal human remains from the Bronze Age Lichtenstein cave in Lower Saxony, Germany. We developed duplex Alu screening PCRs with flanking primers for two Alu elements, each combined with a single internal Alu primer. By adding an internal primer, the approximately 400–500 bp presence signals of Alu elements can be detected within a range of less than 200 bp. Thus, our PCR approach is suited for highly fragmented ancient DNA samples, whereas NGS analyses frequently are unable to handle repetitive elements. With this analysis system, we examined remains of 12 individuals from the Lichtenstein cave with different degrees of DNA degradation. The duplex PCRs showed fully informative amplification results for all of the chosen Alu loci in eight of the 12 samples. Our analysis system showed that Alu presence/absence analysis is possible in samples with different degrees of DNA degradation and it reduces the amount of valuable skeletal material needed by a factor of four, as compared with a singleplex approach.

Genetic Factors of Individual Differences in Decision Making in Economic Behavior: A Japanese Twin Study using the Allais Problem.

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Shikishima, Chizuru; Hiraishi, Kai; Yamagata, Shinji; Ando, Juko; Okada, Mitsuhiro

2015-01-01

Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary) utility even when objective information of probabilities and reward are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more "rational." We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20-47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of "rational" decision making from the perspective of genetic correlations with cognitive abilities.

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

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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.

Measuring genetic knowledge: a brief survey instrument for adolescents and adults.

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Fitzgerald-Butt, S M; Bodine, A; Fry, K M; Ash, J; Zaidi, A N; Garg, V; Gerhardt, C A; McBride, K L

2016-02-01

Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack of a written, English language, validated, published measure has limited our ability to evaluate genetic knowledge of patients and families. Here, we begin the psychometric analysis of a true/false genetic knowledge measure. The 18-item measure was completed by parents of children with congenital heart defects (CHD) (n = 465) and adolescents and young adults with CHD (age: 15-25, n = 196) with a mean total correct score of 12.6 [standard deviation (SD) = 3.5, range: 0-18]. Utilizing exploratory factor analysis, we determined that one to three correlated factors, or abilities, were captured by our measure. Through confirmatory factor analysis, we determined that the two factor model was the best fit. Although it was necessary to remove two items, the remaining items exhibited adequate psychometric properties in a multidimensional item response theory analysis. Scores for each factor were computed, and a sum-score conversion table was derived. We conclude that this genetic knowledge measure discriminates best at low knowledge levels and is therefore well suited to determine a minimum adequate amount of genetic knowledge. However, further reliability testing and validation in diverse research and clinical settings is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

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Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette

2014-01-01

BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children

Institute of Scientific and Technical Information of China (English)

Theresa A Mikhailov; Sylvia E Furner

2009-01-01

Inflammatory bowel disease is a chronic, debilitating disorder of the gastrointestinal tract. The etiology of inflammatory bowel disease has not been elucidated, but is thought to be multifactorial with both environmental and genetic influences. A large body of research has been conducted to elucidate the etiology of inflammatory bowel disease. This article reviews this literature, emphasizing the studies of breastfeeding and the studies of genetic factors, particularly NOD2 polymorphisms.

Genetic and environmental influences on height from infancy to early adulthood

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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...

Genetic distance estimates and variable factors distinguishing between goat Kacang, Muara and Samosir

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Hamdan; Saputra, H.; Mirwandhono, E.; Hasnudi; Sembiring, I.; Umar, S.; Ginting, N.; Alwiyah

2018-02-01

The purpose of this research was to look the genetic distance and factors distinguishing variable betwen types of goats in North Sumatera. This research have been conducted in PayaBakung, Hamparan Perak and Klambir Lima village, Deli Serdang district, Batu Binumbun, Aritonang, HutaGinjang village, Muarasubdistrict, North Tapanuli district and ParbabaDolok, Siopat Sosor, Sinabulan village, Ronggur Nihuta Pangururan village, Sitonggi-tonggi village in the subdistrict RonggurNihuta, Samosir district of the month of July 2016. The data was analyzed using descriptive, discriminants, canonical, Principal Component Analysis, Distance genetic and Tree Phylogenetic. The result showed that the nearest genetic distance goat found in Kacang and Samosir (1.973), and the farthest genetic distnace find in Samosir and Muara (8.671). The variables made it difference was goat race Base Rim Horn (0.856) and Long Horn (0.878). Genetic distance values most far between Muaragoat with Samosir goat was (8.671). The conclude that the crossing superior result, must be cross between two goat types with value genetics most distance. It will have a better chance heterosis in cross result.

Test- and behavior-specific genetic factors affect WKY hypoactivity in tests of emotionality.

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Baum, Amber E; Solberg, Leah C; Churchill, Gary A; Ahmadiyeh, Nasim; Takahashi, Joseph S; Redei, Eva E

2006-05-15

Inbred Wistar-Kyoto rats consistently display hypoactivity in tests of emotional behavior. We used them to test the hypothesis that the genetic factors underlying the behavioral decision-making process will vary in different environmental contexts. The contexts used were the open-field test (OFT), a novel environment with no explicit threats present, and the defensive-burying test (DB), a habituated environment into which a threat has been introduced. Rearing, a voluntary behavior was measured in both tests, and our study was the first to look for genetic loci affecting grooming, a relatively automatic, stress-responsive stereotyped behavior. Quantitative trait locus analysis was performed on a population of 486 F2 animals bred from reciprocal inter-crosses. The genetic architectures of DB and OFT rearing, and of DB and OFT grooming, were compared. There were no common loci affecting grooming behavior in both tests. These different contexts produced the stereotyped behavior via different pathways, and genetic factors seem to influence the decision-making pathways and not the expression of the behavior. Three loci were found that affected rearing behavior in both tests. However, in both contexts, other loci had greater effects on the behavior. Our results imply that environmental context's effects on decision-making vary depending on the category of behavior.

Belief and disbelief in the existence of genetic risk factors for suicide: cross-cultural comparisons.

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Voracek, Martin

2007-12-01

There is evidence for widespread disbelief in the genetics of suicide, despite recent research progress in this area and convergent evidence supporting a role for genetic factors. This study analyzed the beliefs held in 8 samples (total N = 1224) of various types (psychology, medical, and various undergraduates, psychology graduates, and the general population) from 6 countries located on 3 continents (Austria, Canada, Malaysia, Romania, United Kingdom, and the USA). Endorsement rates for the existence of genetic risk factors for suicide ranged from 26% and 30% (Austrian psychology undergraduates and general population) to around 50% (psychology undergraduates in the USA and United Kingdom). In the 8 samples, respondents' sex, age, religiosity, political orientation, and other demographic variables were, for the most part, unrelated, but overall knowledge about suicide throughout was related positively to endorsement rates. Consistent with previous research, across a considerable variety of sample types and cultural settings there was no evidence for a clear majority believing in genetic bases for suicide.

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.

Attitudes and Practices Among Internists Concerning Genetic Testing

Science.gov (United States)

Chung, Wendy; Marder, Karen; Shanmugham, Anita; Chin, Lisa J.; Stark, Meredith; Leu, Cheng-Shiun; Appelbaum, Paul S.

2012-01-01

Many questions remain concerning whether, when, and how physicians order genetic tests, and what factors are involved in their decisions. We surveyed 220 internists from two academic medical centers about their utilization of genetic testing. Rates of genetic utilizations varied widely by disease. Respondents were most likely to have ordered tests for Factor V Leiden (16.8%), followed by Breast/Ovarian Cancer (15.0%). In the past 6 months, 65% had counseled patients on genetic issues, 44% had ordered genetic tests, 38.5% had referred patients to a genetic counselor or geneticist, and 27.5% had received ads from commercial labs for genetic testing. Only 4.5% had tried to hide or disguise genetic information, and genetic discrimination. Only 53.4% knew of a geneticist/genetic counselor to whom to refer patients. Most rated their knowledge as very/somewhat poor concerning genetics (73.7%) and guidelines for genetic testing (87.1%). Most felt needs for more training on when to order tests (79%), and how to counsel patients (82%), interpret results (77.3%), and maintain privacy (80.6%). Physicians were more likely to have ordered a genetic test if patients inquired about genetic testing (pgenetic counselor to whom to refer patients (pgenetic counselor in the past 6 months, had more comfort counseling patients about testing (pgenetics, larger practices (pgenetic discrimination (pgenetic test was associated with patients inquiring about testing, having referred patients to a geneticist/genetic counselor and knowing how to order tests., These data suggest that physicians recognize their knowledge deficits, and are interested in training. These findings have important implications for future medical practice, research, and education. PMID:22585186

Can genetics help psychometrics? Improving dimensionality assessment through genetic factor modeling.

Science.gov (United States)

Franić, Sanja; Dolan, Conor V; Borsboom, Denny; Hudziak, James J; van Beijsterveldt, Catherina E M; Boomsma, Dorret I

2013-09-01

In the present article, we discuss the role that quantitative genetic methodology may play in assessing and understanding the dimensionality of psychological (psychometric) instruments. Specifically, we study the relationship between the observed covariance structures, on the one hand, and the underlying genetic and environmental influences giving rise to such structures, on the other. We note that this relationship may be such that it hampers obtaining a clear estimate of dimensionality using standard tools for dimensionality assessment alone. One situation in which dimensionality assessment may be impeded is that in which genetic and environmental influences, of which the observed covariance structure is a function, differ from each other in structure and dimensionality. We demonstrate that in such situations settling dimensionality issues may be problematic, and propose using quantitative genetic modeling to uncover the (possibly different) dimensionalities of the underlying genetic and environmental structures. We illustrate using simulations and an empirical example on childhood internalizing problems.

Genetic factors of individual differences in decision making in economic behavior: A Japanese twin study using the Allais problem

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Chizuru eShikishima

2015-11-01

Full Text Available Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary utility even when objective information of probabilities and rewards are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more rational. We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20–47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of rational decision making from the perspective of genetic correlations with cognitive abilities.

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...

Identification of genetic elements in metabolism by high-throughput mouse phenotyping

DEFF Research Database (Denmark)

Rozman, Jan; Rathkolb, Birgit; Oestereicher, Manuela A.

2018-01-01

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic da...

Genetics of Vitiligo

Science.gov (United States)

Spritz, Richard; Andersen, Genevieve

2016-01-01

Synopsis Vitiligo is “complex disorder” (also termed polygenic and multifactorial), reflecting simultaneous contributions of multiple genetic risk factors and environmental triggers. Large-scale genome-wide association studies, principally in European-derived whites and in Chinese, have discovered approximately 50 different genetic loci that contribute to vitiligo risk, some of which also contribute to other autoimmune diseases that are epidemiologically associated with vitiligo. At many of these vitiligo susceptibility loci the corresponding relevant genes have now been identified, and for some of these genes the specific DNA sequence variants that contribute to vitiligo risk are also now known. A large fraction of these genes encode proteins involved in immune regulation, a number of others play roles in cellular apoptosis, and still others are involved in regulating functions of melanocytes. For this last group, there appears to be an opposite relationship between susceptibility to vitiligo and susceptibility to melanoma, suggesting that vitiligo may engage a normal mechanism of immune surveillance for melanoma. While many of the specific biologic mechanisms through which these genetic factors operate to cause vitiligo remain to be elucidated, it is now clear that vitiligo is an autoimmune disease involving a complex relationship between programming and function of the immune system, aspects of the melanocyte autoimmune target, and dysregulation of the immune response. PMID:28317533

Demographic history and biologically relevant genetic variation of Native Mexicans inferred from whole-genome sequencing

OpenAIRE

Romero-Hidalgo, Sandra; Ochoa-Leyva, Adrián; Garcíarrubio, Alejandro; Acuña-Alonzo, Victor; Antúnez-Argüelles, Erika; Balcazar-Quintero, Martha; Barquera-Lozano, Rodrigo; Carnevale, Alessandra; Cornejo-Granados, Fernanda; Fernández-López, Juan Carlos; García-Herrera, Rodrigo; García-Ortíz, Humberto; Granados-Silvestre, Ángeles; Granados, Julio; Guerrero-Romero, Fernando

2017-01-01

Understanding the genetic structure of Native American populations is important to clarify their diversity, demographic history, and to identify genetic factors relevant for biomedical traits. Here, we show a demographic history reconstruction from 12 Native American whole genomes belonging to six distinct ethnic groups representing the three main described genetic clusters of Mexico (Northern, Southern, and Maya). Effective population size estimates of all Native American groups remained bel...

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..

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.

Familial resemblance of borderline personality disorder features: genetic or cultural transmission?

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Marijn A Distel

Full Text Available Borderline personality disorder is a severe personality disorder for which genetic research has been limited to family studies and classical twin studies. These studies indicate that genetic effects explain 35 to 45% of the variance in borderline personality disorder and borderline personality features. However, effects of non-additive (dominance genetic factors, non-random mating and cultural transmission have generally not been explored. In the present study an extended twin-family design was applied to self-report data of twins (N = 5,017 and their siblings (N = 1,266, parents (N = 3,064 and spouses (N = 939 from 4,015 families, to estimate the effects of additive and non-additive genetic and environmental factors, cultural transmission and non-random mating on individual differences in borderline personality features. Results showed that resemblance among biological relatives could completely be attributed to genetic effects. Variation in borderline personality features was explained by additive genetic (21%; 95% CI 17-26% and dominant genetic (24%; 95% CI 17-31% factors. Environmental influences (55%; 95% CI 51-60% explained the remaining variance. Significant resemblance between spouses was observed, which was best explained by phenotypic assortative mating, but it had only a small effect on the genetic variance (1% of the total variance. There was no effect of cultural transmission from parents to offspring.

The CogBIAS longitudinal study protocol: cognitive and genetic factors influencing psychological functioning in adolescence.

Science.gov (United States)

Booth, Charlotte; Songco, Annabel; Parsons, Sam; Heathcote, Lauren; Vincent, John; Keers, Robert; Fox, Elaine

2017-12-29

Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.

No Major Host Genetic Risk Factor Contributed to A(H1N12009 Influenza Severity.

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Koldo Garcia-Etxebarria

Full Text Available While most patients affected by the influenza A(H1N1 pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

Science.gov (United States)

Hasler, Gregor; Pinto, Anthony; Greenberg, Benjamin D; Samuels, Jack; Fyer, Abby J; Pauls, David; Knowles, James A; McCracken, James T; Piacentini, John; Riddle, Mark A; Rauch, Scott L; Rasmussen, Steven A; Willour, Virginia L; Grados, Marco A; Cullen, Bernadette; Bienvenu, O Joseph; Shugart, Yin-Yao; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Wang, Ying; Ronquillo, Jonne; Nestadt, Gerald; Murphy, Dennis L

2007-03-01

Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

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

Factor V leiden and ischemic stroke risk: the Genetics of Early Onset Stroke (GEOS) study.

Science.gov (United States)

Hamedani, Ali G; Cole, John W; Cheng, Yuching; Sparks, Mary J; O'Connell, Jeffrey R; Stine, Oscar C; Wozniak, Marcella A; Stern, Barney J; Mitchell, Braxton D; Kittner, Steven J

2013-05-01

Factor V Leiden (FVL) has been associated with ischemic stroke in children but not in adults. Although the FVL mutation is associated with increased risk for venous thrombosis, its association with ischemic stroke in young adults remains uncertain. Therefore, we examined the association between FVL and ischemic stroke in participants of the Genetics of Early Onset Stroke (GEOS) study. A population-based case control study identified 354 women and 476 men 15 to 49 years of age with first-ever ischemic stroke and 907 controls. Participant-specific data included vascular risk factors, FVL genotype and, for cases, the ischemic stroke subtype by modified Trial of ORG 10172 in Acute Stroke criteria. Logistic regression was used to calculate odds ratios for the entire population and for subgroups stratified by risk factors and ischemic stroke subtype. The frequency of the FVL mutation was similar between ischemic stroke patients (3.6%; 95% confidence interval [CI] 2.5%-5.1%) and nonstroke controls (3.8%; 95% CI 2.7%-5.2%). This frequency did not change significantly when cases were restricted to patients with stroke of undetermined etiology (4.1%; 95% CI 2.6%-6.4%). Among young adults, we found no evidence for an association between FVL and either all ischemic stroke or the subgroup with stroke of undetermined etiology. Published by Elsevier Inc.

Who’s Afraid of Math? Two Sources of Genetic Variance for Mathematical Anxiety

Science.gov (United States)

Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A.; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W.; Lyons, Ian M.; Petrill, Stephen A.

2015-01-01

Background Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem-solving and achievement. The present study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Methods Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Results Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and non-familial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. Conclusions The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics, and may extend to other areas of academic achievement. PMID:24611799

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...

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

Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective

OpenAIRE

Martina C. Cornel; Carla G. van El

2017-01-01

More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especia...

Genetics and epigenetics of rheumatoid arthritis

Science.gov (United States)

Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

2013-01-01

Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

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...

What factors impact upon a woman’s decision to undertake genetic cancer testing?

Directory of Open Access Journals (Sweden)

Julie Anne Quinlivan

2014-01-01

Full Text Available Introduction: The advent of human genome project has lead to genetic tests that identify high-risk states for certain cancers. Many are privately marketed on the Internet. Despite the availability of tests, limited data has evaluated factors that lead to test uptake. The aim of the present study was to explore the attitudes of a cohort of new mothers towards uptake of a genetic cancer test with a 50% predictive value of cancer.Methods: A cross-sectional survey was undertaken. The project targeted women who had recently given birth at an Australian tertiary referral hospital. Women were asked about a theoretical blood test that detected an increased risk for the development of cancer. Attitudes and knowledge questionnaires were completed. Results: Of 232 consecutive women approached, 32 declined, giving a response rate of 86.2%. Only 63 (31.5% women stated they would have the test. Absence of religious belief, higher level of education, better knowledge of terms used in genetics, an absence of concern over emotional, employment and insurance discrimination and previous acceptance of Down syndrome screening in pregnancy were each associated with significantly higher rate of test uptake in univariate analysis (all pConclusion: Concern over discrimination and having made a prior decision to have genetic testing were the principal factors associated with decision-making.

GENETIC FACTORS INFLUENCING HEMOGLOBIN F LEVEL IN β-THALASSEMIA/HB E DISEASE.

Science.gov (United States)

Ruangrai, Waraporn; Jindadamrongwech, Sumalee

2016-01-01

Genetic factors influencing Hb F content in adult red blood cells include β-thalassemia genotypes, co-inheritance of α-thalassemia traits and single nucleotide polymorphisms (SNPs). Genotyping of α- and β-thalassemia and five SNPs in β-globin gene cluster previously identified in genome-wide association studies as being markers of elevated Hb F in β-thalassemia were performed in 81 subjects diagnosed with β-thalassemia/Hb E. Hb F levels are higher (0.9-7.1 g/dl) in subjects (n = 57) with the severe compared to mild β-thalassemia (0.8-2.5 g/ dl) (n = 4) genotypes, and are similarly low (0.7-3.5 g/dl) in those (n = 15) with α-thalassemia co-inheritance. Hb F levels in non-thalassemia controls (n = 150) range from 0 to 0.15 g/dl. The presence of homozygous minor alleles of the 5 SNPs are significant indicators of β-thalassemia/Hb E individuals with high Hb F (> 4 g/dl), independent of their thalassemia genotypes. Given that re-activation of γ-globin genes leads to amelioration of β-thalassemia severity, understanding how genetic factors up-regulate Hb F production may lead to possible therapeutic interventions, genetically or pharmacologically, of this debilitating disease in the not too distant future.

The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.

Science.gov (United States)

Wattanachai, Nitsupa; Kaewmoongkun, Sutthida; Pussadhamma, Burabha; Makarawate, Pattarapong; Wongvipaporn, Chaiyasith; Kiatchoosakun, Songsak; Vannaprasaht, Suda; Tassaneeyakul, Wichittra

2017-08-01

The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays. The patients with variant genotypes of VKORC1 - 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability. VKORC1 - 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

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.

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.

Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study.

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Khemiri, L; Kuja-Halkola, R; Larsson, H; Jayaram-Lindström, N

2016-04-01

Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity. Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985. The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors. The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.

The role of ecological and genetic factors in the onset of asthma in children (literature review

Directory of Open Access Journals (Sweden)

Chumachenko N.G.

2016-09-01

Full Text Available The article presents a literature review of publications domestic and foreign authors on the risk factors of the onset of asthma in children. Health is 20–40% dependent on the environment and 35–70% dependent on genetic factors. The interaction of genetic and environmental factors lead to anti-oxidant stress and changes not only on the level of the entire organism, but also on the cellular and molecular level. To asses to prognosis for onset and development of bronchial asthma in children, that reside in environmentally neglected zones it is necessary to continue the research into the molecular-genetic gene polymorphism of the enzymes of the xenobiotic detoxication system, as well as metabolic disturbances in children in order to delineate risk group for the onset of the condition and to develop indications for anti-oxidant treatment, to correct the molecular disturbances, that appear long before the clinical manifestation of asthma.

Familial clustering and genetic risk for dementia in a genetically isolated Dutch population.

NARCIS (Netherlands)

K. Sleegers (Kristel); F. Forey; J. Theuns (Jessie); Y.S. Aulchenko (Yurii); S. Rademakers (Suzanne); M. Cruts (Marc); W.A. van Gool (Willem); P. Heutink (Peter); B.A. Oostra (Ben); J.C. van Swieten (John); C.M. van Duijn (Cornelia); C. van Broeckhoven (Christine)

2004-01-01

textabstractDespite advances in elucidating the genetic epidemiology of Alzheimer's disease and frontotemporal dementia, the aetiology for most patients with dementia remains unclear. We examined the genetic epidemiology of dementia in a recent genetically isolated Dutch population founded around

A National Perspective: An Analysis of Factors That Influence Special Educators to Remain in the Field of Education

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Nickson, Lautrice M.; Kritsonis, William Allan

2006-01-01

The purpose of this article is to analyze factors that influence special educators to remain in the field of education. School administrators are perplexed by the large number of teachers who decide to leave the field of education after three years. The retention rates of special educators' require school administrators to focus on developing a…

Familial clustering and genetic risk for dementia in a genetically isolated Dutch population

NARCIS (Netherlands)

Sleegers, K.; Roks, G.; Theuns, J.; Aulchenko, Y. S.; Rademakers, R.; Cruts, M.; van Gool, W. A.; van Broeckhoven, C.; Heutink, P.; Oostra, B. A.; van Swieten, J. C.; van Duijn, C. M.

2004-01-01

Despite advances in elucidating the genetic epidemiology of Alzheimer's disease and frontotemporal dementia, the aetiology for most patients with dementia remains unclear. We examined the genetic epidemiology of dementia in a recent genetically isolated Dutch population founded around 1750. The

Biology, Genetics, and Environment: Underlying Factors Influencing Alcohol Metabolism.

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Wall, Tamara L; Luczak, Susan E; Hiller-Sturmhöfel, Susanne

2016-01-01

Gene variants encoding several of the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), are among the largest genetic associations with risk for alcohol dependence. Certain genetic variants (i.e., alleles)--particularly the ADH1B*2, ADH1B*3, ADH1C*1, and ALDH2*2 alleles--have been associated with lower rates of alcohol dependence. These alleles may lead to an accumulation of acetaldehyde during alcohol metabolism, which can result in heightened subjective and objective effects. The prevalence of these alleles differs among ethnic groups; ADH1B*2 is found frequently in northeast Asians and occasionally Caucasians, ADH1B*3 is found predominantly in people of African ancestry, ADH1C*1 varies substantially across populations, and ALDH2*2 is found almost exclusively in northeast Asians. Differences in the prevalence of these alleles may account at least in part for ethnic differences in alcohol consumption and alcohol use disorder (AUD). However, these alleles do not act in isolation to influence the risk of AUD. For example, the gene effects of ALDH2*2 and ADH1B*2 seem to interact. Moreover, other factors have been found to influence the extent to which these alleles affect a person's alcohol involvement, including developmental stage, individual characteristics (e.g., ethnicity, antisocial behavior, and behavioral undercontrol), and environmental factors (e.g., culture, religion, family environment, and childhood adversity).

Glucose levels and genetic variants across transcriptional pathways: interaction effects with BMI

NARCIS (Netherlands)

Povel, C.M.; Feskens, E.J.M.; Imholz, S.; Blaak, E.E.; Boer, J.M.A.; Dollé, M.E.T.

2010-01-01

Objective: Much of the genetic variation in glucose levels remains to be discovered. Especially, research on gene–environment interactions is scarce. Overweight is one of the main risk factors for hyperglycemia. As transcriptional regulation is important for both weight maintenance and glucose

Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors.

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Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro

2013-01-01

Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

Who is afraid of math? Two sources of genetic variance for mathematical anxiety.

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Wang, Zhe; Hart, Sara Ann; Kovas, Yulia; Lukowski, Sarah; Soden, Brooke; Thompson, Lee A; Plomin, Robert; McLoughlin, Grainne; Bartlett, Christopher W; Lyons, Ian M; Petrill, Stephen A

2014-09-01

Emerging work suggests that academic achievement may be influenced by the management of affect as well as through efficient information processing of task demands. In particular, mathematical anxiety has attracted recent attention because of its damaging psychological effects and potential associations with mathematical problem solving and achievement. This study investigated the genetic and environmental factors contributing to the observed differences in the anxiety people feel when confronted with mathematical tasks. In addition, the genetic and environmental mechanisms that link mathematical anxiety with math cognition and general anxiety were also explored. Univariate and multivariate quantitative genetic models were conducted in a sample of 514 12-year-old twin siblings. Genetic factors accounted for roughly 40% of the variation in mathematical anxiety, with the remaining being accounted for by child-specific environmental factors. Multivariate genetic analyses suggested that mathematical anxiety was influenced by the genetic and nonfamilial environmental risk factors associated with general anxiety and additional independent genetic influences associated with math-based problem solving. The development of mathematical anxiety may involve not only exposure to negative experiences with mathematics, but also likely involves genetic risks related to both anxiety and math cognition. These results suggest that integrating cognitive and affective domains may be particularly important for mathematics and may extend to other areas of academic achievement. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Genetic and environmental factors influencing the Placental Growth Factor (PGF) variation in two populations

DEFF Research Database (Denmark)

Sorice, Rossella; Ruggiero, Daniela; Nutile, Teresa

2012-01-01

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...

No Major Host Genetic Risk Factor Contributed to A(H1N1)2009 Influenza Severity.

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Garcia-Etxebarria, Koldo; Bracho, María Alma; Galán, Juan Carlos; Pumarola, Tomàs; Castilla, Jesús; Ortiz de Lejarazu, Raúl; Rodríguez-Dominguez, Mario; Quintela, Inés; Bonet, Núria; Garcia-Garcerà, Marc; Domínguez, Angela; González-Candelas, Fernando; Calafell, Francesc

2015-01-01

While most patients affected by the influenza A(H1N1) pandemic experienced mild symptoms, a small fraction required hospitalization, often without concomitant factors that could explain such a severe course. We hypothesize that host genetic factors could contribute to aggravate the disease. To test this hypothesis, we compared the allele frequencies of 547,296 genome-wide single nucleotide polymorphisms (SNPs) between 49 severe and 107 mild confirmed influenza A cases, as well as against a general population sample of 549 individuals. When comparing severe vs. mild influenza A cases, only one SNP was close to the conventional p = 5×10-8. This SNP, rs28454025, sits in an intron of the GSK233 gene, which is involved in a neural development, but seems not to have any connections with immunological or inflammatory functions. Indirectly, a previous association reported with CD55 was replicated. Although sample sizes are low, we show that the statistical power in our design was sufficient to detect highly-penetrant, quasi-Mendelian genetic factors. Hence, and assuming that rs28454025 is likely to be a false positive, no major genetic factor was detected that could explain poor influenza A course.

Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors

Directory of Open Access Journals (Sweden)

Hyun Chul Lee

2012-06-01

Full Text Available Postrenal transplantation diabetes mellitus (PTDM, or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, β-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced β-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

Factors influencing parents' decision to donate their healthy infant's DNA for minimal-risk genetic research.

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Hatfield, Linda A; Pearce, Margaret M

2014-11-01

To examine factors that influence a parent's decision to donate their healthy infant's DNA for minimal-risk genetic research. Grounded theory, using semi-structured interviews conducted with 35 postpartum mother or mother-father dyads in an urban teaching hospital. Data were collected from July 2011 to January 2012. Audiorecorded semistructured interviews were conducted in private rooms with mothers or mother-father dyads 24 to 48 hr after the birth of their healthy, full-term infant. Data-driven content analysis using selected principles of grounded theory was performed. Parents' willingness to donate their healthy infant's DNA for minimal-risk pediatric genetic research emerged as a process involving three interacting components: the parents, the scientist, and the comfort of the child embedded within the context of benefit to the child. The purpose of the study and parents' perception of their commitment of time and resources determined their willingness to participate. The scientist's ability to communicate trust in the research process influenced parents' decisions. Physical discomfort of the child shaped parents' decision to donate DNA. Parental perception of a direct benefit to their child affected their willingness to discuss genetic research and its outcomes. Significant gaps and misunderstandings in parental knowledge of pediatric genetic research may affect parental willingness to donate their healthy child's DNA. Nurses knowledgeable about the decision-making process parents utilize to donate their healthy infant's DNA for minimal-risk genetic research and the factors influencing that decision are well positioned to educate parents about the role of genetics in health and illness and reassure potential research participants of the value and safeguards in pediatric genetic research. © 2014 Sigma Theta Tau International.

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry.

Science.gov (United States)

Guidi, Monia; Foletti, Giuseppe; McLaren, Paul; Cavassini, Matthias; Rauch, Andri; Tarr, Philip E; Lamy, Olivier; Panchaud, Alice; Telenti, Amalio; Csajka, Chantal; Rotger, Margalida

2015-01-01

Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow-up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analysed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40 ng/ml during 12 months of follow-up and several dosage regimens were evaluated by simulation. A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/ritonavir and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the inter-individual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates, and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300,000 IU two times per year. This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors

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Naoyuki eSato

2013-11-01

Full Text Available It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD. Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of 1 compromised vascular reactivity, 2 vascular lesions, 3 hypo/hyperglycemia, and 4 exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. Beta-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: 1 functional MRI or SPECT for cerebrovascular reactivity, 2 MRI for ischemic lesions and atrophy, 3 clinical episodes of hypoglycemia and hyperglycemia, 4 amyloid-PET and tau-PET for pathological features of AD, would be required.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

Science.gov (United States)

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

Molecular Genetic of Atopic dermatitis: An Update

Science.gov (United States)

Al-Shobaili, Hani A.; Ahmed, Ahmed A.; Alnomair, Naief; Alobead, Zeiad Abdulaziz; Rasheed, Zafar

2016-01-01

Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date. PMID:27004062

Clinical and genetic factors associated with suicide in mood disorder patients.

Science.gov (United States)

Antypa, Niki; Souery, Daniel; Tomasini, Mario; Albani, Diego; Fusco, Federica; Mendlewicz, Julien; Serretti, Alessandro

2016-03-01

Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the 'Psy Pluriel' center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.

COMPARATIVE EVALUATION OF RISK FACTORS FOR CARDIOVASCULAR DISEASE (CVD) IN GENETICALLY PREDISPOSED RATS

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Rodent CVD models are increasingly used for understanding individual differences in susceptibility to environmental stressors such as air pollution. We characterized pathologies and a number of known human risk factors of CVD in genetically predisposed, male young adult Spontaneo...

Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women

DEFF Research Database (Denmark)

Mehta, Divya; Tropf, Felix C; Gratten, Jacob

2016-01-01

IMPORTANCE: A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due......), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014. CONCLUSIONS AND RELEVANCE: This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported...

Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations.

Science.gov (United States)

Anastasiou, Evilena; Mitchell, Piers D

2013-10-01

The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

The relationships between chemical and genetic differentiation and environmental factors across the distribution of Erigeron breviscapus (Asteraceae).

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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

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...

Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk.

Science.gov (United States)

Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn

2017-07-01

Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.

Bacteria, genetics and irritable bowel syndrome.

LENUS (Irish Health Repository)

Craig, Orla F

2010-06-01

EVALUATION OF: Villani AC, Lemire M, Thabane M et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 138, 1502-1513 (2010). While the pathogenesis of irritable bowel syndrome (IBS) remains to be fully defined, two clinical observations - the occurrence, de novo, of IBS following bacterial gastroenteritis and the history, commonly obtained from IBS patients, of other instances of the syndrome within their families - have instigated investigations, in IBS, of the potential roles, on the one hand, of the gut microbiota and the host response and, on the other hand, of genetic factors. The study reviewed here relates to both of these factors by studying genetic predisposition to postinfective IBS in a large population of individuals who were exposed to a multimicrobial enteric infection, which resulted in a severe outbreak of gastroenteritis and was followed by the development of IBS in over a third. In this detailed study, the investigators identified a number of genes that were linked significantly to the development of postinfectious-IBS in the Toll-like receptor 9, IL-6 and cadherin 1 regions. These genes play important roles in bacterial recognition, the inflammatory response and epithelial integrity, respectively, and provide considerable support for the hypothesis that links IBS onset to disturbances in the microbiota and the host response.

Why Agricultural Educators Remain in the Classroom

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Crutchfield, Nina; Ritz, Rudy; Burris, Scott

2013-01-01

The purpose of this study was to identify and describe factors that are related to agricultural educator career retention and to explore the relationships between work engagement, work-life balance, occupational commitment, and personal and career factors as related to the decision to remain in the teaching profession. The target population for…

Inspirations in medical genetics.

Science.gov (United States)

Asadollahi, Reza

2016-02-01

There are abundant instances in the history of genetics and medical genetics to illustrate how curiosity, charisma of mentors, nature, art, the saving of lives and many other matters have inspired great discoveries. These achievements from deciphering genetic concepts to characterizing genetic disorders have been crucial for management of the patients. There remains, however, a long pathway ahead. © The Author(s) 2014.

Genetic regulation of the variation of circulating insulin-like growth factors and leptin in human pedigrees.

Science.gov (United States)

Pantsulaia, Ia; Pantsulaia, I; Trofimov, Svetlana; Kobyliansky, Eugene; Livshits, Gregory

2005-07-01

Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% +/- 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and 0.15 +/- 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.

The attitudes of Dutch fertility specialists towards the addition of genetic testing in screening of tubal factor infertility.

Science.gov (United States)

Malogajski, Jelena; Jansen, Marleen E; Ouburg, Sander; Ambrosino, Elena; Terwee, Caroline B; Morré, Servaas A

2017-06-01

This study aims to identify elements perceived by Dutch fertility specialists as barriers and facilitators for the introduction of genetic testing, and their attitudes towards the use of genetic information. The genetic test would be implemented in routine screening for tubal pathology and identifies SNPs relevant for the immune response causing tubal pathology. Experienced reproductive specialists working in Dutch Academic Hospitals were interviewed. Based on the results of four interviews a questionnaire was developed and used to survey medical doctors in six out of eight Dutch Academic hospitals. 60.4% (n=91) stated that the addition of genetic markers to the Chlamydia trachomatis antibody test (CAT) in screening for tubal pathology would increase screening accuracy. 68.2% (n=90) agreed they would require additional training on clinical genetics. Clinical utility (91.2%, n=91) and cost-effectiveness (95.6%, n=91) were recognized by the respondents as important factors in gaining support for the new screening strategy. In summary, respondents showed a positive attitude towards the implementation of a genetic test combined with CAT for tubal factor infertility (TFI) screening. To gain their support the majority of respondents agreed that clinical utility, specifically cost-effectiveness, is an important factor. Comprehensive research about economic implications and utility regarding the introduction of genomic markers should be the next step in the implementation strategy. Furthermore, education and training would need to be developed and offered to fertility care professionals about genetic markers, their interpretation, and implications for clinical decision-making. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetics of Congenital Heart Disease: Past and Present.

Science.gov (United States)

Muntean, Iolanda; Togănel, Rodica; Benedek, Theodora

2017-04-01

Congenital heart disease is the most common congenital anomaly, representing an important cause of infant morbidity and mortality. Congenital heart disease represents a group of heart anomalies that include septal defects, valve defects, and outflow tract anomalies. The exact genetic, epigenetic, or environmental basis of congenital heart disease remains poorly understood, although the exact mechanism is likely multifactorial. However, the development of new technologies including copy number variants, single-nucleotide polymorphism, next-generation sequencing are accelerating the detection of genetic causes of heart anomalies. Recent studies suggest a role of small non-coding RNAs, micro RNA, in congenital heart disease. The recently described epigenetic factors have also been found to contribute to cardiac morphogenesis. In this review, we present past and recent genetic discoveries in congenital heart disease.

Characterization of clinical and genetic risk factors associated with dyslipidemia after kidney transplantation.

Science.gov (United States)

Numakura, Kazuyuki; Kagaya, Hideaki; Yamamoto, Ryohei; Komine, Naoki; Saito, Mitsuru; Hiroshi, Tsuruta; Akihama, Susumu; Inoue, Takamitsu; Narita, Shintaro; Tsuchiya, Norihiko; Habuchi, Tomonori; Niioka, Takenori; Miura, Masatomo; Satoh, Shigeru

2015-01-01

We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012) and prednisolone (P = 0.023) doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8-12.2). These findings may aid in predicting a patient's risk of developing dyslipidemia.

Characterization of Clinical and Genetic Risk Factors Associated with Dyslipidemia after Kidney Transplantation

Science.gov (United States)

Numakura, Kazuyuki; Kagaya, Hideaki; Yamamoto, Ryohei; Komine, Naoki; Saito, Mitsuru; Hiroshi, Tsuruta; Akihama, Susumu; Narita, Shintaro; Tsuchiya, Norihiko; Habuchi, Tomonori; Niioka, Takenori; Miura, Masatomo; Satoh, Shigeru

2015-01-01

We determined the prevalence of dyslipidemia in a Japanese cohort of renal allograft recipients and investigated clinical and genetic characteristics associated with having the disease. In total, 126 patients that received renal allograft transplants between February 2002 and August 2011 were studied, of which 44 recipients (34.9%) were diagnosed with dyslipidemia at 1 year after transplantation. Three clinical factors were associated with a risk of having dyslipidemia: a higher prevalence of disease observed among female than male patients (P = 0.021) and treatment with high mycophenolate mofetil (P = 0.012) and prednisolone (P = 0.023) doses per body weight at 28 days after transplantation. The genetic association between dyslipidemia and 60 previously described genetic polymorphisms in 38 putative disease-associated genes was analyzed. The frequency of dyslipidemia was significantly higher in patients with the glucocorticoid receptor (NR3C1) Bcl1 G allele than in those with the CC genotype (P = 0.001). A multivariate analysis revealed that the NR3C1 Bcl1 G allele was a significant risk factor for the prevalence of dyslipidemia (odds ratio = 4.6; 95% confidence interval = 1.8–12.2). These findings may aid in predicting a patient's risk of developing dyslipidemia. PMID:25944971

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrio, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Silgado, Julio C. Cardona; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniete; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L.; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Gruenblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Restrepo, Sandra C. Mesa; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlo N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosario, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Duarte, Ana V. Valencia; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Routeau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson B.; Stewart, Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Neale, Benjamin M; Davis, Lea K; Gamazon, Eric R; Derks, Eske M; Evans, Patrick; Edlund, Christopher K; Crane, Jacquelyn; Fagerness, Jesen A; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O Joseph; Black, Donald W; Bloch, Michael H; Brentani, Helena; Bruun, Ruth D; Budman, Cathy L; Camarena, Beatriz; Campbell, Desmond D; Cappi, Carolina; Silgado, Julio C Cardona; Cavallini, Maria C; Chavira, Denise A; Chouinard, Sylvain; Cook, Edwin H; Cookson, M R; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L; Girard, Simon L; Grabe, Hans J; Grados, Marco A; Greenberg, Benjamin D; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A; Hemmings, Sian M J; Herrera, Luis D; Hezel, Dianne M; Hoekstra, Pieter J; Jankovic, Joseph; Kennedy, James L; King, Robert A; Konkashbaev, Anuar I; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T; Mesa Restrepo, Sandra C; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L; Naarden, Allan L; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A; Pakstis, Andrew J; Pato, Michele T; Pato, Carlos N; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L; Renner, Tobias; Reus, Victor I; Richter, Margaret A; Riddle, Mark A; Robertson, Mary M; Romero, Roxana; Rosário, Maria C; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S; Samuels, Jack; Sandor, Paul; Service, Susan K; Sheppard, Brooke; Singer, Harvey S; Smit, Jan H|info:eu-repo/dai/nl/113700644; Stein, Dan J; Strengman, Eric; Tischfield, Jay A; Turiel, Maurizio; Valencia Duarte, Ana V; Vallada, Homero; Veenstra-VanderWeele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R; Westenberg, Herman G M; Shugart, Yin Yao; Hounie, Ana G; Miguel, Euripedes C; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C|info:eu-repo/dai/nl/194111423; McMahon, William; Posthuma, Danielle; Oostra, Ben A; Nestadt, Gerald; Rouleau, Guy A; Purcell, Shaun; Jenike, Michael A; Heutink, Peter; Hanna, Gregory L; Conti, David V; Arnold, Paul D; Freimer, Nelson B; Stewart, S Evelyn; Knowles, James A; Cox, Nancy J; Pauls, David L

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Cusi, Daniele; Delorme, Richard; Denys, D.; Dion, Yves; Eapen, Valsama; Heutink, Peter; Cox, Nancy J; Pauls, David L

OBJECTIVE: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons

OpenAIRE

Rotger, Margalida; Glass, Tracy R; Junier, Thomas; Lundgren, Jens; Neaton, James D; Poloni, Estella S; van 't Wout, Angélique B; Lubomirov, Rubin; Colombo, Sara; Martinez, Raquel; Rauch, Andri; Günthard, Huldrych F; Neuhaus, Jacqueline; Wentworth, Deborah; van Manen, Danielle

2013-01-01

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the ...

Cannabis Beyond Good and Evil. How genetic and epidemiological factors shape the relationship between cannabis and psychosis

NARCIS (Netherlands)

Schubart, C.D.

2013-01-01

The studies presented in this thesis aimed to identify genetic and non-genetic (epidemiological) factors that shape the association between cannabis use and psychosis. We showed that the age of first use of cannabis is a determinant for the strength of the association between cannabis use and

Importance of genetic factors in the occurrence of epilepsy syndrome type: a twin study

DEFF Research Database (Denmark)

Corey, Linda A; Pellock, John M; Kjeldsen, Marianne J

2011-01-01

not appear to play an important role in determining risk for frontal, occipital or temporal lobe epilepsy. These results suggest that, while genetic factors contribute to risk for major syndrome types, determined when possible, their contribution to risk for localization-related syndrome sub......Although there is strong evidence that genetic factors contribute to risk for epilepsy, their role in the determination of syndrome type is less clear. This study was undertaken to address this question. Information related to epilepsy was obtained from twins included in 455 monozygotic and 868...... dizygotic pairs ascertained from population-based twin registries in Denmark, Norway and the United States. Syndrome type was determined based on medical record information and detailed clinical interviews and classified using the International Classification Systems for the Epilepsies and Epileptic...

Genetic factors influence the clustering of depression among individuals with lower socioeconomic status

NARCIS (Netherlands)

S. López León (Sandra); W.C. Choy (Wing Chi); Y.S. Aulchenko (Yurii); S. Claes (Stephan); B.A. Oostra (Ben); J.P. Mackenbach (Johan); C.M. van Duijn (Cornelia); A.C.J.W. Janssens (Cécile)

2009-01-01

textabstractObjective: To investigate the extent to which shared genetic factors can explain the clustering of depression among individuals with lower socioeconomic status, and to examine if neuroticism or intelligence are involved in these pathways. Methods: In total 2,383 participants (1,028 men

Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD

NARCIS (Netherlands)

Yu, D.M.; Mathews, C.A.; Scharf, J.M.; Neale, B.M.; Davis, L.K.; Gamazon, E.R.; Derks, E.M.; Evans, P.; Edlund, C.K.; Crane, J.; Osiecki, L.; Gallagher, P.; Gerber, G.; Haddad, S.; Illmann, C.; McGrath, L.M.; Mayerfeld, C.; Arepalli, S.; Barlassina, C.; Barr, C.L.; Bellodi, L.; Benarroch, F.; Berrio, G.B.; Bienvenu, O.J.; Black, D.W.; Bloch, M.H.; Brentani, H.; Bruun, R.D.; Budman, C.L.; Camarena, B.; Campbell, D.D.; Cappi, C.; Silgado, J.C.C.; Cavallini, M.C.; Chavira, D.A.; Chouinard, S.; Cook, E.H.; Cookson, M.R.; Coric, V.; Cullen, B.; Cusi, D.; Delorme, R.; Denys, D.; Dion, Y.; Eapen, V.; Egberts, K.; Falkai, P.; Fernandez, T.; Fournier, E.; Garrido, H.; Geller, D.; Gilbert, D.L.; Girard, S.L.; Grabe, H.J.; Grados, M.A.; Greenberg, B.D.; Gross-Tsur, V.; Grunblatt, E.; Hardy, J.; Heiman, G.A.; Hemmings, S.M.J.; Herrera, L.D.; Hezel, D.M.; Hoekstra, P.J.; Jankovic, J.; Kennedy, J.L.; King, R.A.; Konkashbaev, A.I.; Kremeyer, B.; Kurlan, R.; Lanzagorta, N.; Leboyer, M.; Leckman, J.F.; Lennertz, L.; Liu, C.Y.; Lochner, C.; Lowe, T.L.; Lupoli, S.; Macciardi, F.; Maier, W.; Manunta, P.; Marconi, M.; McCracken, J.T.; Restrepo, S.C.M.; Moessner, R.; Moorjani, P.; Morgan, J.; Muller, H.; Murphy, D.L.; Naarden, A.L.; Nurmi, E.; Ochoa, W.C.; Ophoff, R. A.; Pakstis, A.J.; Pato, M.T.; Pato, C.N.; Piacentini, J.; Pittenger, C.; Pollak, Y.; Smit, J.H.; Posthuma, D.; Cox, N.J.; Pauls, D.L.

2015-01-01

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identi fication of definitive susceptibility genes for these etiologically complex disorders remains elusive. The

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.

The five-factor model of personality and borderline personality disorder: a genetic analysis of comorbidity.

Science.gov (United States)

Distel, Marijn A; Trull, Timothy J; Willemsen, Gonneke; Vink, Jacqueline M; Derom, Catherine A; Lynskey, Michael; Martin, Nicholas G; Boomsma, Dorret I

2009-12-15

Recently, the nature of personality disorders and their relationship with normal personality traits has received extensive attention. The five-factor model (FFM) of personality, consisting of the personality traits neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness, is one of the proposed models to conceptualize personality disorders as maladaptive variants of continuously distributed personality traits. The present study examined the phenotypic and genetic association between borderline personality and FFM personality traits. Data were available for 4403 monozygotic twins, 4425 dizygotic twins, and 1661 siblings from 6140 Dutch, Belgian, and Australian families. Broad-sense heritability estimates for neuroticism, agreeableness, conscientiousness, extraversion, openness to experience, and borderline personality were 43%, 36%, 43%, 47%, 54%, and 45%, respectively. Phenotypic correlations between borderline personality and the FFM personality traits ranged from .06 for openness to experience to .68 for neuroticism. Multiple regression analyses showed that a combination of high neuroticism and low agreeableness best predicted borderline personality. Multivariate genetic analyses showed the genetic factors that influence individual differences in neuroticism, agreeableness, conscientiousness, and extraversion account for all genetic liability to borderline personality. Unique environmental effects on borderline personality, however, were not completely shared with those for the FFM traits (33% is unique to borderline personality). Borderline personality shares all genetic variation with neuroticism, agreeableness, conscientiousness, and extraversion. The unique environmental influences specific to borderline personality may cause individuals with a specific pattern of personality traits to cross a threshold and develop borderline personality.

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

Complex interactions between dietary and genetic factors impact lycopene metabolism and distribution

Science.gov (United States)

Moran, Nancy E.; Erdman, John W.; Clinton, Steven K.

2013-01-01

Intake of lycopene, a red, tetraterpene carotenoid found in tomatoes is epidemiologically associated with a decreased risk of chronic disease processes, and lycopene has demonstrated bioactivity in numerous in vitro and animal models. However, our understanding of absorption, tissue distribution, and biological impact in humans remains very limited. Lycopene absorption is strongly impacted by dietary composition, especially the amount of fat. Concentrations of circulating lycopene in lipoproteins may be further influenced by a number of variations in genes related to lipid absorption and metabolism. Lycopene is not uniformly distributed among tissues, with adipose, liver, and blood being the major body pools, while the testes, adrenals, and liver have the greatest concentrations compared to other organs. Tissue concentrations of lycopene are likely dictated by expression of and genetic variation in lipoprotein receptors, cholesterol transporters, and carotenoid metabolizing enzymes, thus impacting lycopene accumulation at target sites of action. The novel application of genetic evaluation in concert with lycopene tracers will allow determination of which genes and polymorphisms define individual lycopene metabolic phenotypes, response to dietary variables, and ultimately determine biological and clinical outcomes. A better understanding of the relationship between diet, genetics, and lycopene distribution will provide necessary information to interpret epidemiological findings more accurately and to design effective, personalized clinical nutritional interventions addressing hypotheses regarding health outcomes. PMID:23845854

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD

NARCIS (Netherlands)

Yu, Dongmei; Mathews, Carol A.; Scharf, Jeremiah M.; Neale, Benjamin M.; Davis, Lea K.; Gamazon, Eric R.; Derks, Eske M.; Evans, Patrick; Edlund, Christopher K.; Crane, Jacquelyn; Fagerness, Jesen A.; Osiecki, Lisa; Gallagher, Patience; Gerber, Gloria; Haddad, Stephen; Illmann, Cornelia; McGrath, Lauren M.; Mayerfeld, Catherine; Arepalli, Sampath; Barlassina, Cristina; Barr, Cathy L.; Bellodi, Laura; Benarroch, Fortu; Berrió, Gabriel Bedoya; Bienvenu, O. Joseph; Black, Donald W.; Bloch, Michael H.; Brentani, Helena; Bruun, Ruth D.; Budman, Cathy L.; Camarena, Beatriz; Campbell, Desmond D.; Cappi, Carolina; Silgado, Julio C. Cardona; Cavallini, Maria C.; Chavira, Denise A.; Chouinard, Sylvain; Cook, Edwin H.; Cookson, M. R.; Coric, Vladimir; Cullen, Bernadette; Cusi, Daniele; Delorme, Richard; Denys, Damiaan; Dion, Yves; Eapen, Valsama; Egberts, Karin; Falkai, Peter; Fernandez, Thomas; Fournier, Eduardo; Garrido, Helena; Geller, Daniel; Gilbert, Donald L.; Girard, Simon L.; Grabe, Hans J.; Grados, Marco A.; Greenberg, Benjamin D.; Gross-Tsur, Varda; Grünblatt, Edna; Hardy, John; Heiman, Gary A.; Hemmings, Sian M. J.; Herrera, Luis D.; Hezel, Dianne M.; Hoekstra, Pieter J.; Jankovic, Joseph; Kennedy, James L.; King, Robert A.; Konkashbaev, Anuar I.; Kremeyer, Barbara; Kurlan, Roger; Lanzagorta, Nuria; Leboyer, Marion; Leckman, James F.; Lennertz, Leonhard; Liu, Chunyu; Lochner, Christine; Lowe, Thomas L.; Lupoli, Sara; Macciardi, Fabio; Maier, Wolfgang; Manunta, Paolo; Marconi, Maurizio; McCracken, James T.; Mesa Restrepo, Sandra C.; Moessner, Rainald; Moorjani, Priya; Morgan, Jubel; Muller, Heike; Murphy, Dennis L.; Naarden, Allan L.; Nurmi, Erika; Ochoa, William Cornejo; Ophoff, Roel A.; Pakstis, Andrew J.; Pato, Michele T.; Pato, Carlos N.; Piacentini, John; Pittenger, Christopher; Pollak, Yehuda; Rauch, Scott L.; Renner, Tobias; Reus, Victor I.; Richter, Margaret A.; Riddle, Mark A.; Robertson, Mary M.; Romero, Roxana; Rosário, Maria C.; Rosenberg, David; Ruhrmann, Stephan; Sabatti, Chiara; Salvi, Erika; Sampaio, Aline S.; Samuels, Jack; Sandor, Paul; Service, Susan K.; Sheppard, Brooke; Singer, Harvey S.; Smit, Jan H.; Stein, Dan J.; Strengman, Eric; Tischfield, Jay A.; Turiel, Maurizio; Valencia Duarte, Ana V.; Vallada, Homero; Veenstra-Vanderweele, Jeremy; Walitza, Susanne; Wang, Ying; Weale, Mike; Weiss, Robert; Wendland, Jens R.; Westenberg, Herman G. M.; Shugart, Yin Yao; Hounie, Ana G.; Miguel, Euripedes C.; Nicolini, Humberto; Wagner, Michael; Ruiz-Linares, Andres; Cath, Danielle C.; McMahon, William; Posthuma, Danielle; Oostra, Ben A.; Nestadt, Gerald; Rouleau, Guy A.; Purcell, Shaun; Jenike, Michael A.; Heutink, Peter; Hanna, Gregory L.; Conti, David V.; Arnold, Paul D.; Freimer, Nelson B.; Stewart, S. Evelyn; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

2015-01-01

Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a

High genetic diversity in a potentially vulnerable tropical tree species despite extreme habitat loss.

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Annika M E Noreen

Full Text Available Over the last 150 years, Singapore's primary forest has been reduced to less than 0.2% of its previous area, resulting in extinctions of native flora and fauna. Remaining species may be threatened by genetic erosion and inbreeding. We surveyed >95% of the remaining primary forest in Singapore and used eight highly polymorphic microsatellite loci to assess genetic diversity indices of 179 adults (>30 cm stem diameter, 193 saplings (>1 yr, and 1,822 seedlings (<1 yr of the canopy tree Koompassia malaccensis (Fabaceae. We tested hypotheses relevant to the genetic consequences of habitat loss: (1 that the K. malaccensis population in Singapore experienced a genetic bottleneck and a reduction in effective population size, and (2 K. malaccensis recruits would exhibit genetic erosion and inbreeding compared to adults. Contrary to expectations, we detected neither a population bottleneck nor a reduction in effective population size, and high genetic diversity in all age classes. Genetic diversity indices among age classes were not significantly different: we detected overall high expected heterozygosity (He = 0.843-0.854, high allelic richness (R = 16.7-19.5, low inbreeding co-efficients (FIS = 0.013-0.076, and a large proportion (30.1% of rare alleles (i.e. frequency <1%. However, spatial genetic structure (SGS analyses showed significant differences between the adults and the recruits. We detected significantly greater SGS intensity, as well as higher relatedness in the 0-10 m distance class, for seedlings and saplings compared to the adults. Demographic factors for this population (i.e. <200 adult trees are a cause for concern, as rare alleles could be lost due to stochastic factors. The high outcrossing rate (tm = 0.961, calculated from seedlings, may be instrumental in maintaining genetic diversity and suggests that pollination by highly mobile bee species in the genus Apis may provide resilience to acute habitat loss.

Impact of Geography and Climate on the Genetic Differentiation of the Subtropical Pine Pinus yunnanensis.

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Wang, Baosheng; Mao, Jian-Feng; Zhao, Wei; Wang, Xiao-Ru

2013-01-01

Southwest China is a biodiversity hotspot characterized by complex topography, heterogeneous regional climates and rich flora. The processes and driving factors underlying this hotspot remain to be explicitly tested across taxa to gain a general understanding of the evolution of biodiversity and speciation in the region. In this study, we examined the role played by historically neutral processes, geography and environment in producing the current genetic diversity of the subtropical pine Pinus yunnanensis. We used genetic and ecological methods to investigate the patterns of genetic differentiation and ecological niche divergence across the distribution range of this species. We found both continuous genetic differentiation over the majority of its range, and discrete isolated local clusters. The discrete differentiation between two genetic groups in the west and east peripheries is consistent with niche divergence and geographical isolation of these groups. In the central area of the species' range, population structure was shaped mainly by neutral processes and geography rather than by ecological selection. These results show that geographical and environmental factors together created stronger and more discrete genetic differentiation than isolation by distance alone, and illustrate the importance of ecological factors in forming or maintaining genetic divergence across a complex landscape. Our findings differ from other phylogenetic studies that identified the historical drainage system in the region as the primary factor shaping population structure, and highlight the heterogeneous contributions that geography and environment have made to genetic diversity among taxa in southwest China.

The relationships between chemical and genetic differentiation and environmental factors across the distribution of Erigeron breviscapus (Asteraceae.

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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

Relationships among walleye population characteristics and genetic diversity in northern Wisconsin Lakes

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Waterhouse, Matthew D.; Sloss, Brian L.; Isermann, Daniel A.

2014-01-01

The maintenance of genetic integrity is an important goal of fisheries management, yet little is known regarding the effects of management actions (e.g., stocking, harvest regulations) on the genetic diversity of many important fish species. Furthermore, relationships between population characteristics and genetic diversity remain poorly understood. We examined relationships among population demographics (abundance, recruitment, sex ratio, and mean age of the breeding population), stocking intensity, and genetic characteristics (heterozygosity, effective number of alleles, allelic richness, Wright's inbreeding coefficient, effective population size [Ne], mean d2 [a measure of inbreeding], mean relatedness, and pairwise population ΦST estimates) for 15 populations of Walleye Sander vitreus in northern Wisconsin. We also tested for potential demographic and genetic influences on Walleye body condition and early growth. Combinations of demographic variables explained 47.1–79.8% of the variation in genetic diversity. Skewed sex ratios contributed to a reduction in Ne and subsequent increases in genetic drift and relatedness among individuals within populations; these factors were correlated to reductions in allelic richness and early growth rate. Levels of inbreeding were negatively related to both age-0 abundance and mean age, suggesting Ne was influenced by recruitment and generational overlap. A negative relationship between the effective number of alleles and body condition suggests stocking affected underlying genetic diversity of recipient populations and the overall productivity of the population. These relationships may result from poor performance of stocked fish, outbreeding depression, or density-dependent factors. An isolation-by-distance pattern of genetic diversity was apparent in nonstocked populations, but was disrupted in stocked populations, suggesting that stocking affected genetic structure. Overall, demographic factors were related to genetic

Genetic factors account for most of the variation in serum tryptase—a twin study

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Sverrild, Asger; van der Sluis, Sophie; Kyvik, Kirsten Ohm

2013-01-01

Background: Mast cells are involved in a number of diseases, including inflammatory diseases such as asthma. Tryptase is a known marker of mast cell burden and activity. However, little is known about the genetic influence on serum tryptase variation. Also, only few and conflicting data exist...... on serum tryptase in asthma. Objective: To estimate the overall contribution of genetic and environmental factors to the variation in serum tryptase and to examine the correlation between serum tryptase and asthma, rhinitis, markers of allergy, airway inflammation, and airway hyperresponsiveness (AHR...

Relationship between genetic and environmental factors and hypercholesterolemia in children.

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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.

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

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Bonnie N Young

Full Text Available Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs. We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

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Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

Genetics and other factors in the aetiology of female pattern hair loss.

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Redler, Silke; Messenger, Andrew G; Betz, Regina C

2017-06-01

Pattern hair loss is the most common form of hair loss in both women and men. Male pattern hair loss, also termed male androgenetic alopecia (M-AGA), is an androgen-dependent trait that is predominantly genetically determined. Androgen-mediated mechanisms are probably involved in female pattern hair loss (FPHL) in some women but the evidence is less strong than in M-AGA; other non-androgenic pathways, including environmental influences, may contribute to the aetiology. Genome-wide association studies have identified several genetic loci for M-AGA and have provided better insight into the underlying biology. However, the role of heritable factors in Female Pattern Hair Loss (FPHL) is largely unknown. Recently published studies have been restricted to candidate gene approaches and could not clearly identify any susceptibility locus/gene for FPHL but suggest that the aetiology differs substantially from that of M-AGA. Hypotheses about possible pathomechanisms of FPHL as well as the results of the genetic studies performed to date are summarized. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exploring Relationships among Belief in Genetic Determinism, Genetics Knowledge, and Social Factors

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Gericke, Niklas; Carver, Rebecca; Castéra, Jérémy; Evangelista, Neima Alice Menezes; Marre, Claire Coiffard; El-Hani, Charbel N.

2017-01-01

Genetic determinism can be described as the attribution of the formation of traits to genes, where genes are ascribed more causal power than what scientific consensus suggests. Belief in genetic determinism is an educational problem because it contradicts scientific knowledge, and is a societal problem because it has the potential to foster…

Role of Genetic and Environmental Factors in the Development of Empathy

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Yudina T.O.,

2017-08-01

Full Text Available The paper provides a review of studies on factors influencing empathy development in early childhood and on conditions promoting manifestation of empathy in children later in life. The outcomes of several studies shed light on the character of empathic response at early stages of child development, particularly in infancy and toddlerhood. This review covers research on the role of biological factors and mechanisms in empathy development (for instance, features of temperament and neuronal bases, as well as research on the relationship between genetic and environmental factors in the development of empathy in ontogenesis. Another part of the paper describes studies on the role of social conditions in the development of empathy in childhood: it focuses primarily on family relations and, in particular, on the mother/child relationship. The paper concludes with several suggestions concerning further research of the specified problem.

Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective

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Martina C. Cornel

2017-08-01

Full Text Available More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especially in relatives. Some 5% of breast cancers and colorectal cancers are attributable to an inherited predisposition. These cancers occur at a relatively young age. DNA testing of relatives of affected patients may facilitate primary and secondary prevention. Training of non-genetic health care workers and health technology assessment are needed, as is translational research in terms of bringing genomics to health care practice while monitoring and evaluating. Stratified screening programs could include cascade screening and risk assessment based on family history. New roles and responsibilities will emerge. A clear assessment of the values implied is needed allowing to balance the pros and cons of interventions to further the responsible innovation of genetic services.

Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective.

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Cornel, Martina C; van El, Carla G

2017-01-01

More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especially in relatives. Some 5% of breast cancers and colorectal cancers are attributable to an inherited predisposition. These cancers occur at a relatively young age. DNA testing of relatives of affected patients may facilitate primary and secondary prevention. Training of non-genetic health care workers and health technology assessment are needed, as is translational research in terms of bringing genomics to health care practice while monitoring and evaluating. Stratified screening programs could include cascade screening and risk assessment based on family history. New roles and responsibilities will emerge. A clear assessment of the values implied is needed allowing to balance the pros and cons of interventions to further the responsible innovation of genetic services.

About 42% of 154 remains from the "Battle of Le Mans", France (1793) belong to women and children: Morphological and genetic evidence.

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Thèves, Catherine; Cabot, Elodie; Bouakaze, Caroline; Chevet, Pierre; Crubézy, Éric; Balaresque, Patricia

2016-05-01

Mass graves were discovered in Le Mans and 154 skeletons were exhumed, representing a remarkable historical series of human remains from western France. We aimed to characterise the age-class and sex of these subjects, and to determine whether their profile fits with that of the Catholic and Royal Army of Vendée, who fought against the Republican Army during the Battle of Le Mans (12th-13th December, 1793). This atypical army was composed of male soldiers, but also of civilian people who followed the troops, including the elderly, children and women. In total 154 skeletons from nine mass graves were exhumed from 2009 to 2010. Two morphological methods were used to determine the sex of the subjects: the Probabilist Sexual Diagnosis (DSP) and Secondary Sexual Diagnosis (DSS) methods. Samples were handled cautiously to avoid any pre-laboratory contamination. Molecular genetic sex-typing using a recently developed assay was used to maximise sex-diagnosis of the ancient DNA samples, and 97 successful profiles including immatures were generated. Using morphological and genetic data combined, we successfully determined the sex of 93% of the subjects; 62% were male and 31% female. About 87% of subjects could be considered adults (>18 years old), 6% adolescents (15-19 years old) and 7% infants (Catholic and Royal Army) or passively (collateral victims from the civilian population of Le Mans). They represent 5-6% of the estimated 2500-3000 victims. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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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.

Genetics and Other Risk Factors for Past Concussions in Active-Duty Soldiers.

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Dretsch, Michael N; Silverberg, Noah; Gardner, Andrew J; Panenka, William J; Emmerich, Tanja; Crynen, Gogce; Ait-Ghezala, Ghania; Chaytow, Helena; Mathura, Venkat; Crawford, Fiona C; Iverson, Grant L

2017-02-15

Risk factors for concussion in active-duty military service members are poorly understood. The present study examined the association between self-reported concussion history and genetics (apolipoprotein E [APOE], brain-derived neurotrophic factor [BDNF], and D2 dopamine receptor genes [DRD2]), trait personality measures (impulsive-sensation seeking and trait aggression-hostility), and current alcohol use. The sample included 458 soldiers who were preparing to deploy for Operation Iraqi Freedom/Operation Enduring Freedom. For those with the BDNF Met/Met genotype, 57.9% (11/19) had a history of one or more prior concussions, compared with 35.6% (154/432) of those with other BDNF genotypes (p = 0.049, odds ratio [OR] = 2.48). APOE and DRD2 genotypes were not associated with risk for past concussions. Those with the BDNF Met/Met genotype also reported greater aggression and hostility personality characteristics. When combined in a predictive model, prior military deployments, being male, and having the BDNF Met/Met genotype were independently associated with increased lifetime history of concussions in active-duty soldiers. Replication in larger independent samples is necessary to have more confidence in both the positive and negative genetic associations reported in this study.

Modelling individual space?time exposure opportunities: A novel approach to unravelling the genetic or environment disease causation debate

DEFF Research Database (Denmark)

Sabel, Clive E; Boyle, Paul; Raab, Gillian

2009-01-01

The aetiology of Amyotrophic Lateral Sclerosis (ALS) is uncertain. While around 10% is assumed to be inherited, the relative influence of genetic versus physical or social environmental factors (or some combination of the two) has yet to be determined. A previous study identified significant...... clustering of ALS at the time of birth in south-east Finland and this could support either a genetic or an environmental hypothesis. We know that south-east Finland is an environmentally degraded area, but the population in this region may also be genetically susceptible to this condition. We therefore...... remaining in south-east Finland is more common among cases than controls and, hence, whether there may be an environmental or genetic influence on ALS associated with that region. Our results indeed suggest that the cases were more likely to remain in south-east Finland after birth, compared...

The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop

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D. Pagliari

2015-01-01

Full Text Available Celiac disease (CD is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

Is the Experience of Thermal Pain Genetics Dependent?

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Emilia Horjales-Araujo

2015-01-01

Full Text Available It is suggested that genetic variations explain a significant portion of the variability in pain perception; therefore, increased understanding of pain-related genetic influences may identify new targets for therapies and treatments. The relative contribution of the different genes to the variance in clinical and experimental pain responses remains unknown. It is suggested that the genetic contributions to pain perception vary across pain modalities. For example, it has been suggested that more than 60% of the variance in cold pressor responses can be explained by genetic factors; in comparison, only 26% of the variance in heat pain responses is explained by these variations. Thus, the selection of pain model might markedly influence the magnitude of the association between the pain phenotype and genetic variability. Thermal pain sensation is complex with multiple molecular and cellular mechanisms operating alone and in combination within the peripheral and central nervous system. It is thus highly probable that the thermal pain experience is affected by genetic variants in one or more of the pathways involved in the thermal pain signaling. This review aims to present and discuss some of the genetic variations that have previously been associated with different experimental thermal pain models.

Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilities.

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Lobo, Daniela S S; Kennedy, James L

2009-09-01

To summarize and discuss findings from genetic studies conducted on pathological gambling (PG). Searches were conducted on PubMed and PsychInfo databases using the keywords: 'gambling and genes', 'gambling and family' and 'gambling and genetics', yielding 18 original research articles investigating the genetics of PG. Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50-60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life-events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems. Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies.

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

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Ornoy, Asher; Weinstein-Fudim, Liza; Ergaz, Zivanit

2016-01-01

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not all are "clean" of different confounding factors. The

DTREEv2, a computer-based support system for the risk assessment of genetically modified plants

NARCIS (Netherlands)

Pertry, I.; Nothegger, C.; Sweet, J.; Kuiper, H.A.; Davies, H.; Iserentant, D.; Hull, R.; Mezzetti, B.; Messens, K.; Loose, De M.; Oliveira, de D.; Burssens, S.; Gheysen, G.; Tzotzos, G.

2014-01-01

Risk assessment of genetically modified organisms (GMOs) remains a contentious area and a major factor influencing the adoption of agricultural biotech. Methodologically, in many countries, risk assessment is conducted by expert committees with little or no recourse to databases and expert systems

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.

Sudden infant death syndrome, childhood thrombosis, and presence of genetic risk factors for thrombosis

DEFF Research Database (Denmark)

Larsen, T B; Nørgaard-Pedersen, B; Banner, Jytte

2000-01-01

in the child. This prompted us to investigate these genetic markers of thromboembolic disease in 121 cases of sudden infant death syndrome and in relevant controls, in the expectation of a more frequent occurrence of these markers if thrombosis is an etiological factor in sudden infant death syndrome......Sudden infant death syndrome or "cot death" has until the late eighties been a significant cause of death in children between the ages of 1 month and 1 year. Approximately two per 1000 children born alive dies of sudden infant death syndrome each year in Western Europe, North America, and Australia....... The vulnerability of the infant brain stem to ischemia has been suggested to be a conceivable cause of sudden infant death syndrome. This is compatible with a hypothesis that genetic risk factors for cerebral thrombosis could cause microinfarction in the brain stem during the first month of life, affecting vital...

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

[Research progress in genetic abnormalities and etiological factors of congenital anorectal malformation].

Science.gov (United States)

Zhang, Yanli; Ren, Hongxia

2016-01-01

Congenital anorectal malformation (ARM) is one of the most common gastrointestinal congenital diseases, accounting for 1/4 in digestive tract malformation, and is one of the congenital malformations in routine surveillance by the World Health Organization. Because of the variety of risk factors and the complexity of the pathological changes, etiology of ARM is still not clear. It is mostly considered that ARM is resulted from hereditary factors and environmental factors in the development of embryogenesis. Through animal experiments, scholars have found that Hox, Shh, Fgf, Wnt, Cdx and TCF4, Eph and ephrin play crucial role during the development of digestive tract. When the genes/signaling pathway dysfunction occurs, ARM may happen. In addition, ARM is related to the external factors in pregnancy. Because of the complexity of related factors in the development of human embryogenesis, the research progress of human ARM is very slow. This paper reviews relevant literatures in genetic factors and environmental factors, in order to provide the theoretical basis for the treatment and prevention of ARM.

Human Genetics of Diabetic Retinopathy: Current Perspectives

Directory of Open Access Journals (Sweden)

Daniel P. K. Ng

2010-01-01

Full Text Available Diabetic retinopathy (DR is a most severe microvascular complication which, if left unchecked, can be sight-threatening. With the global prevalence of diabetes being relentlessly projected to rise to 438 million subjects by 2030, DR will undoubtedly pose a major public health concern. Efforts to unravel the human genetics of DR have been undertaken using the candidate gene and linkage approaches, while GWAS efforts are still lacking. Aside from evidence for a few genes including aldose reductase and vascular endothelial growth factor, the genetics of DR remain poorly elucidated. Nevertheless, the promise of impactful scientific discoveries may be realized if concerted and collaborative efforts are mounted to identify the genes for DR. Harnessing new genetic technologies and resources such as the upcoming 1000 Genomes Project will help advance this field of research, and potentially lead to a rich harvest of insights into the biological mechanisms underlying this debilitating complication.

Is Chronic Low Back Pain Associated with the Prevalence of Coronary Heart Disease when Genetic Susceptibility Is Considered?

DEFF Research Database (Denmark)

Fernandez, Matt; Ordoñana, Juan R; Hartvigsen, Jan

2016-01-01

OBJECTIVE: To investigate the chronic low back pain and coronary heart disease relationship, after adjusting for relevant confounders, including genetics. METHODS: In a cross-sectional design, 2148 twins were recruited from the Murcia Twin Registry, Spain. The exposure was chronic LBP...... twin pairs discordant for chronic LBP utilised, separated for zygosity-dizygotic (DZ) and monozygotic (MZ) pairs, which adjusted for shared familial factors, including genetics. RESULTS: Chronic LBP pain is associated with lifetime myocardial infarction [odds ratio (OR) = 2.69, 95% confidence interval...... of the association remained or increased in the co-twin control analyses, none reached statistical significance. CONCLUSION: Chronic LBP is associated with a higher prevalence of myocardial infarction and coronary heart disease. It is possible that this association remains even when controlling for genetics...

Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.

Science.gov (United States)

Marchi, Nina; Hegay, Tatyana; Mennecier, Philippe; Georges, Myriam; Laurent, Romain; Whitten, Mark; Endicott, Philipp; Aldashev, Almaz; Dorzhu, Choduraa; Nasyrova, Firuza; Chichlo, Boris; Ségurel, Laure; Heyer, Evelyne

2017-04-01

Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure. © 2017 Wiley Periodicals, Inc.

Association of substance use disorders with childhood trauma but not African genetic heritage in an African American cohort.

Science.gov (United States)

Ducci, Francesca; Roy, Alec; Shen, Pei-Hong; Yuan, Qiaoping; Yuan, Nicole P; Hodgkinson, Colin A; Goldman, Lynn R; Goldman, David

2009-09-01

Genetic variation influences differential vulnerability to addiction within populations. However, it remains unclear whether differences in frequencies of vulnerability alleles contribute to disparities between populations and to what extent ancestry correlates with differential exposure to environmental risk factors, including poverty and trauma. The authors used 186 ancestry-informative markers to measure African ancestry in 407 addicts and 457 comparison subjects self-identified as African Americans. The reference group was 1,051 individuals from the Human Genome Diversity Cell Line Panel, which includes 51 diverse populations representing most worldwide genetic diversity. African Americans varied in degrees of African, European, Middle Eastern, and Central Asian genetic heritage. The overall level of African ancestry was actually smaller among cocaine, opiate, and alcohol addicts (proportion=0.76-0.78) than nonaddicted African American comparison subjects (proportion=0.81). African ancestry was associated with living in impoverished neighborhoods, a factor previously associated with risk. There was no association between African ancestry and exposure to childhood abuse or neglect, a factor that strongly predicted all types of addictions. These results suggest that African genetic heritage does not increase the likelihood of genetic risk for addictions. They highlight the complex interrelation between genetic ancestry and social, economic, and environmental conditions and the strong relation of those factors to addiction. Studies of epidemiological samples characterized for genetic ancestry and social, psychological, demographic, economic, cultural, and historical factors are needed to better disentangle the effects of genetic and environmental factors underlying interpopulation differences in vulnerability to addiction and other health disparities.

The conservation genetics juggling act: Integrating genetics and ecology, science and policy

Science.gov (United States)

Haig, Susan M.; Miller, Mark P.; Bellinger, Renee; Draheim, Hope M.; Mercer, Dacey; Mullins, Tom

2016-01-01

The field of conservation genetics, when properly implemented, is a constant juggling act integrating molecular genetics, ecology, and demography with applied aspects concerning managing declining species or implementing conservation laws and policies. This young field has grown substantially since the 1980’s following development of the polymerase chain reaction and now into the genomics era. Our lab has “grown up” with the field, having worked on these issues for over three decades. Our multi-disciplinary approach entails understanding the behavior and ecology of species as well as the underlying processes that contribute to genetic viability. Taking this holistic approach provides a comprehensive understanding of factors that influence species persistence and evolutionary potential while considering annual challenges that occur throughout their life cycle. As a federal lab, we are often addressing the needs of the U.S. Fish and Wildlife Service in their efforts to list, de-list or recover species. Nevertheless, there remains an overall communication gap between research geneticists and biologists who are charged with implementing their results. Therefore, we outline the need for a National Center for Small Population Biology to ameliorate this problem and provide organizations charged with making status decisions firmer ground from which to make their critical decisions. 

Determination of genetic relatedness from low-coverage human genome sequences using pedigree simulations.

Science.gov (United States)

Martin, Michael D; Jay, Flora; Castellano, Sergi; Slatkin, Montgomery

2017-08-01

We develop and evaluate methods for inferring relatedness among individuals from low-coverage DNA sequences of their genomes, with particular emphasis on sequences obtained from fossil remains. We suggest the major factors complicating the determination of relatedness among ancient individuals are sequencing depth, the number of overlapping sites, the sequencing error rate and the presence of contamination from present-day genetic sources. We develop a theoretical model that facilitates the exploration of these factors and their relative effects, via measurement of pairwise genetic distances, without calling genotypes, and determine the power to infer relatedness under various scenarios of varying sequencing depth, present-day contamination and sequencing error. The model is validated by a simulation study as well as the analysis of aligned sequences from present-day human genomes. We then apply the method to the recently published genome sequences of ancient Europeans, developing a statistical treatment to determine confidence in assigned relatedness that is, in some cases, more precise than previously reported. As the majority of ancient specimens are from animals, this method would be applicable to investigate kinship in nonhuman remains. The developed software grups (Genetic Relatedness Using Pedigree Simulations) is implemented in Python and freely available. © 2017 John Wiley & Sons Ltd.

Assessing educational priorities in genetics for general practitioners and specialists in five countries: factor structure of the Genetic-Educational Priorities (Gen-EP) scale.

NARCIS (Netherlands)

Calefato, J.M.; Nippert, I.; Harris, H.J.; Kristoffersson, U.; Schmidtke, J.; Kate, L.P. ten; Anionwu, E.; Benjamin, C.; Challen, K.; Plass, A.M.; Harris, R.; Julian-Reynier, C.

2008-01-01

Purpose: A scale assessing primary care physicians' priorities for genetic education (The Gen-EP scale) was developed and tested in five European countries. The objective of this study was to determine its factor structure, to test scaling assumptions and to determine internal consistency. Methods:

Population cycles: generalities, exceptions and remaining mysteries

Science.gov (United States)

2018-01-01

Population cycles are one of nature's great mysteries. For almost a hundred years, innumerable studies have probed the causes of cyclic dynamics in snowshoe hares, voles and lemmings, forest Lepidoptera and grouse. Even though cyclic species have very different life histories, similarities in mechanisms related to their dynamics are apparent. In addition to high reproductive rates and density-related mortality from predators, pathogens or parasitoids, other characteristics include transgenerational reduced reproduction and dispersal with increasing-peak densities, and genetic similarity among populations. Experiments to stop cyclic dynamics and comparisons of cyclic and noncyclic populations provide some understanding but both reproduction and mortality must be considered. What determines variation in amplitude and periodicity of population outbreaks remains a mystery. PMID:29563267

Population genetic structure and conservation genetics of threatened Okaloosa darters (Etheostoma okaloosae).

Science.gov (United States)

Austin, James D.; Jelks, Howard L.; Tate, Bill; Johnson, Aria R.; Jordan, Frank

2011-01-01

Imperiled Okaloosa darters (Etheostoma okaloosae) are small, benthic fish limited to six streams that flow into three bayous of Choctawhatchee Bay in northwest Florida, USA. We analyzed the complete mitochondrial cytochrome b gene and 10 nuclear microsatellite loci for 255 and 273 Okaloosa darters, respectively. Bayesian clustering analyses and AMOVA reflect congruent population genetic structure in both mitochondrial and microsatellite DNA. This structure reveals historical isolation of Okaloosa darter streams nested within bayous. Most of the six streams appear to have exchanged migrants though they remain genetically distinct. The U.S. Fish and Wildlife Service recently reclassified Okaloosa darters from endangered to threatened status. Our genetic data support the reclassification of Okaloosa darter Evolutionary Significant Units (ESUs) in the larger Tom's, Turkey, and Rocky creeks from endangered to threatened status. However, the three smaller drainages (Mill, Swift, and Turkey Bolton creeks) remain at risk due to their small population sizes and anthropogenic pressures on remaining habitat. Natural resource managers now have the evolutionary information to guide recovery actions within and among drainages throughout the range of the Okaloosa darter.

Beyond the genetic basis of sensation seeking: The influence of birth order, family size and parenting styles

OpenAIRE

Feij, Jan A,; Taris, Toon W.

2010-01-01

Genetic analyses of sensation seeking have shown fairly high heritabilities for measures of this trait. However, 40 to 60% of the variance remains unexplained by genetic factors. This longitudinal study examines the influence of characteristics of the family environment -- birth order, family size, socio-economic status and parenting styles -- on two dimensions of sensation seeking: disinhibition and boredom susceptibility. Previous research has shown that these dimensions load on the same fa...

Identifying Associations Between Brain Imaging Phenotypes and Genetic Factors via A Novel Structured SCCA Approach.

Science.gov (United States)

Du, Lei; Zhang, Tuo; Liu, Kefei; Yan, Jingwen; Yao, Xiaohui; Risacher, Shannon L; Saykin, Andrew J; Han, Junwei; Guo, Lei; Shen, Li

2017-06-01

Brain imaging genetics attracts more and more attention since it can reveal associations between genetic factors and the structures or functions of human brain. Sparse canonical correlation analysis (SCCA) is a powerful bi-multivariate association identification technique in imaging genetics. There have been many SCCA methods which could capture different types of structured imaging genetic relationships. These methods either use the group lasso to recover the group structure, or employ the graph/network guided fused lasso to find out the network structure. However, the group lasso methods have limitation in generalization because of the incomplete or unavailable prior knowledge in real world. The graph/network guided methods are sensitive to the sign of the sample correlation which may be incorrectly estimated. We introduce a new SCCA model using a novel graph guided pairwise group lasso penalty, and propose an efficient optimization algorithm. The proposed method has a strong upper bound for the grouping effect for both positively and negatively correlated variables. We show that our method performs better than or equally to two state-of-the-art SCCA methods on both synthetic and real neuroimaging genetics data. In particular, our method identifies stronger canonical correlations and captures better canonical loading profiles, showing its promise for revealing biologically meaningful imaging genetic associations.

Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.

Science.gov (United States)

Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J

2016-04-01

Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. Copyright © 2016. Published by Elsevier Ltd.

Genetic susceptibility factors for multiple chemical sensitivity revisited

DEFF Research Database (Denmark)

Berg, Nikolaj Drimer; Rasmussen, Henrik Berg; Linneberg, Allan

2010-01-01

of this study was to investigate genetic susceptibility factors for MCS and self-reported chemical sensitivity in a population sample. Ninety six MCS patients and 1,207 controls from a general population divided into four severity groups of chemical sensitivity were genotyped for variants in the genes encoding......Multiple chemical sensitivity (MCS) is characterised by adverse effects due to exposure to low levels of chemical substances. Various genes, especially genes of importance to the metabolism of xenobiotic compounds, have been associated with MCS, but findings are inconsistent. The purpose...... significant (OR=1.2, p=0.28). Fast arylamine N-acetyltransferase 2 metaboliser status was associated with severity of chemical sensitivity only in the most severely affected group in the population sample (OR=3.1, p=0.04). The cholecystokinin 2 receptor allele with 21 CT repeats was associated with MCS when...

Small effect of genetic factors on neck pain in old age: a study of 2,108 Danish twins 70 years of age and older

DEFF Research Database (Denmark)

Hartvigsen, Jan; Petersen, Hans Christian; Frederiksen, Henrik

2005-01-01

STUDY DESIGN: Classic twin study. OBJECTIVES: To determine the heritability of neck pain in persons 70 years of age and older. SUMMARY OF BACKGROUND DATA: Previous studies have shown a moderate effect of genetic factors on back pain in the elderly. Genetic influence on neck pain in old age...... calculated and compared for monozygotic and dizygotic twins. Further, heritability estimates were calculated using bivariate probit estimation. RESULTS: A total of 2,108 twin individuals, including 1,054 complete twin pairs, answered the question related to neck pain at intake into the Longitudinal Study...... environmental risk factors (rheumatoid arthritis, osteoarthritis, disc prolapse, and coronary heart disease) showed no significant additive genetic, dominant genetic, or common environmental effects. CONCLUSION: Genetic factors do not play an important role in the liability to neck pain in persons 70 years...

Genetics of human body size and shape: pleiotropic and independent genetic determinants of adiposity.

Science.gov (United States)

Livshits, G; Yakovenko, K; Ginsburg, E; Kobyliansky, E

1998-01-01

The present study utilized pedigree data from three ethnically different populations of Kirghizstan, Turkmenia and Chuvasha. Principal component analysis was performed on a matrix of genetic correlations between 22 measures of adiposity, including skinfolds, circumferences and indices. Findings are summarized as follows: (1) All three genetic matrices were not positive definite and the first four factors retained even after exclusion RG > or = 1.0, explained from 88% to 97% of the total additive genetic variation in the 22 trials studied. This clearly emphasizes the massive involvement of pleiotropic gene effects in the variability of adiposity traits. (2) Despite the quite natural differences in pairwise correlations between the adiposity traits in the three ethnically different samples under study, factor analysis revealed a common basic pattern of covariability for the adiposity traits. In each of the three samples, four genetic factors were retained, namely, the amount of subcutaneous fat, the total body obesity, the pattern of distribution of subcutaneous fat and the central adiposity distribution. (3) Genetic correlations between the retained four factors were virtually non-existent, suggesting that several independent genetic sources may be governing the variation of adiposity traits. (4) Variance decomposition analysis on the obtained genetic factors leaves no doubt regarding the substantial familial and (most probably genetic) effects on variation of each factor in each studied population. The similarity of results in the three different samples indicates that the findings may be deemed valid and reliable descriptions of the genetic variation and covariation pattern of adiposity traits in the human species.

Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

International Nuclear Information System (INIS)

Williams, J.R.; D'Arpa, P.

1981-01-01

DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes

DEFF Research Database (Denmark)

Vaag, Allan; Brøns, Charlotte; Gillberg, Linn

2014-01-01

Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal...... factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between...... life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic...

A transcription factor for cold sensation!

Directory of Open Access Journals (Sweden)

Milbrandt Jeffrey

2005-03-01

Full Text Available Abstract The ability to feel hot and cold is critical for animals and human beings to survive in the natural environment. Unlike other sensations, the physiology of cold sensation is mostly unknown. In the present study, we use genetically modified mice that do not express nerve growth factor-inducible B (NGFIB to investigate the possible role of NGFIB in cold sensation. We found that genetic deletion of NGFIB selectively affected behavioral responses to cold stimuli while behavioral responses to noxious heat or mechanical stimuli were normal. Furthermore, behavioral responses remained reduced or blocked in NGFIB knockout mice even after repetitive application of cold stimuli. Our results provide strong evidence that the first transcription factor NGFIB determines the ability of animals to respond to cold stimulation.

Validation of reported genetic risk factors for periodontitis in a large-scale replication study

NARCIS (Netherlands)

Schaefer, A.S.; Bochenek, G.; Manke, T.; Nothnagel, M.; Graetz, C.; Thien, A.; Jockel-Schneider, Y.; Harks, I.; Staufenbiel, I.; Wijmenga, C.; Eberhard, J.; Guzeldemir-Akcakanat, E.; Cine, N.; Folwaczny, M.; Noack, B.; Meyle, J.; Eickholz, P.; Trombelli, L.; Scapoli, C.; Nohutcu, R.; Bruckmann, C.; Doerfer, C.; Jepsen, S.; Loos, B.G.; Schreiber, S.

2013-01-01

Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441

Validation of reported genetic risk factors for periodontitis in a large-scale replication study

NARCIS (Netherlands)

Schaefer, Arne S.; Bochenek, Gregor; Manke, Thomas; Nothnagel, Michael; Graetz, Christian; Thien, Anneke; Jockel-Schneider, Yvonne; Harks, Inga; Staufenbiel, Ingmar; Wijmenga, Cisca; Eberhard, Joerg; Guzeldemir-Akcakanat, Esra; Cine, Naci; Folwaczny, Mathias; Noack, Barbara; Meyle, Joerg; Eickholz, Peter; Trombelli, Leonardo; Scapoli, Chiara; Nohutcu, Rahime; Bruckmann, Corinna; Doerfer, Christof; Jepsen, Soren; Loos, Bruno G.; Schreiber, Stefan

Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441

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.

Interaction between common breast cancer susceptibility variants, genetic ancestry, and nongenetic risk factors in Hispanic women.

Science.gov (United States)

Fejerman, Laura; Stern, Mariana C; John, Esther M; Torres-Mejía, Gabriela; Hines, Lisa M; Wolff, Roger K; Baumgartner, Kathy B; Giuliano, Anna R; Ziv, Elad; Pérez-Stable, Eliseo J; Slattery, Martha L

2015-11-01

Most genetic variants associated with breast cancer risk have been discovered in women of European ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene-environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by ancestry interaction in this population. We estimated genetic ancestry with a set of 104 ancestry-informative markers selected to discriminate between Indigenous American and European ancestry. We used logistic regression models to evaluate main effects and interactions. We found that the rs13387042-2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74-1.20), 1.20 (0.94-1.53), and 1.49 (1.28-1.75) for current, former, and never hormone therapy users, respectively, Pinteraction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72-1.42), 1.19 (0.98-1.45), and 1.69 (1.26-2.26) for never, 12 months breastfeeding, respectively, Pinteraction 0.014]. The correlation between genetic ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and genetic ancestry in Hispanic women. These results highlight the importance of understanding the interplay between genetic ancestry, genetics, and nongenetic risk factors and their contribution to breast cancer risk. ©2015 American Association for Cancer Research.

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Directory of Open Access Journals (Sweden)

Sjur Reppe

Full Text Available Bone Mineral Density (BMD is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR method to identify single nucleotide polymorphisms (SNPs associated with BMD by leveraging cardiovascular disease (CVD associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.

Non-genetic factors affecting growth performance and carcass ...

African Journals Online (AJOL)

Bekezela

There is a paucity of information on non-genetic ... herds. These data were obtained from the Integrated Recording and Genetic Information Systems .... performance is determined by muscle fibre characteristics (Larzul et al., 1997), which are ...

Genetic susceptibility factors for alcohol-induced chronic pancreatitis.

Science.gov (United States)

Aghdassi, Ali A; Weiss, F Ulrich; Mayerle, Julia; Lerch, Markus M; Simon, Peter

2015-07-01

Chronic pancreatitis is a progressive inflammatory disease of the pancreas and frequently associated with immoderate alcohol consumption. Since only a small proportion of alcoholics eventually develop chronic pancreatitis genetic susceptibility factors have long been suspected to contribute to the pathogenesis of the disease. Smaller studies in ethnically defined populations have found that not only polymorphism in proteins involved in the metabolism of ethanol, such as Alcohol Dehydrogenase and Aldehyde Dehydrogenase, can confer a risk for developing chronic pancreatitis but also mutations that had previously been reported in association with idiopathic pancreatitis, such as SPINK1 mutations. In a much broader approach employing genome wide search strategies the NAPS study found that polymorphisms in the Trypsin locus (PRSS1 rs10273639), and the Claudin 2 locus (CLDN2-RIPPLY1-MORC4 locus rs7057398 and rs12688220) confer an increased risk of developing alcohol-induced pancreatitis. These results from North America have now been confirmed by a European consortium. In another genome wide approach polymorphisms in the genes encoding Fucosyltransferase 2 (FUT2) non-secretor status and blood group B were not only found in association with higher serum lipase levels in healthy volunteers but also to more than double the risk for developing alcohol-associated chronic pancreatitis. These novel genetic associations will allow to investigate the pathophysiological and biochemical basis of alcohol-induced chronic pancreatitis on a cellular level and in much more detail than previously possible. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Genetic Diversity and Spatial Genetic Structure of the Grassland Perennial Saxifraga granulata along Two River Systems.

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Sascha van der Meer

Full Text Available Due to changes in land use, the natural habitats of an increasing number of plant species have become more and more fragmented. In landscapes that consist of patches of suitable habitat, the frequency and extent of long-distance seed dispersal can be expected to be an important factor determining local genetic diversity and regional population structure of the remaining populations. In plant species that are restricted to riparian habitats, rivers can be expected to have a strong impact on the dynamics and spatial genetic structure of populations as they may enable long-distance seed dispersal and thus maintain gene flow between fragmented populations. In this study, we used polymorphic microsatellite markers to investigate the genetic diversity and the spatial genetic structure of 28 populations of Saxifraga granulata along two rivers in central Belgium. We hypothesized that rivers might be essential for gene flow among increasingly isolated populations of this species. Genetic diversity was high (HS = 0.68, which to a certain extent can be explained by the octoploid nature of S. granulata in the study area. Populations along the Dijle and Demer rivers were also highly differentiated (G"ST = 0.269 and 0.164 and DEST = 0.190 and 0.124, respectively and showed significant isolation-by-distance, indicating moderate levels of gene flow primarily between populations that are geographically close to each other. Along the river Demer population genetic diversity was higher upstream than downstream, suggesting that seed dispersal via the water was not the primary mode of dispersal. Overall, these results indicate that despite increasing fragmentation populations along both rivers were highly genetically diverse. The high ploidy level and longevity of S. granulata have most likely buffered negative effects of fragmentation on genetic diversity and the spatial genetic structure of populations in riparian grasslands.

Climatic factors, genetic structure and phenotypic variation in English yew (Taxus baccata L.)

OpenAIRE

Mayol, Maria; Berganzo, Elisa; Burgarella, Concetta; González-Martínez, Santiago C.; Grivet, Delphine; Vendramin, Giovanni G.; Vincenot, Lucie; Riba, Miquel

2018-01-01

Influence of climatic factors on genetic structure and phenotypic variation in English yew (Taxus baccata L.) Conference "Adapting to global change in the Mediterranean hotspot" (Seville, 18-20 September 2013) Mediterranean forests constitute long-term reservoirs of biodiversity and adaptive potential. As compared with their central or northern European counterparts, Mediterranean forests are characterized by highly heterogeneous and fragmented environments, ...

Pediatric chronic pancreatitis is associated with genetic risk factors and substantial disease burden.

Science.gov (United States)

Schwarzenberg, Sarah Jane; Bellin, Melena; Husain, Sohail Z; Ahuja, Monika; Barth, Bradley; Davis, Heather; Durie, Peter R; Fishman, Douglas S; Freedman, Steven D; Gariepy, Cheryl E; Giefer, Matthew J; Gonska, Tanja; Heyman, Melvin B; Himes, Ryan; Kumar, Soma; Morinville, Veronique D; Lowe, Mark E; Nuehring, Neil E; Ooi, Chee Y; Pohl, John F; Troendle, David; Werlin, Steven L; Wilschanski, Michael; Yen, Elizabeth; Uc, Aliye

2015-04-01

To determine the clinical presentation, diagnostic variables, risk factors, and disease burden in children with chronic pancreatitis. We performed a cross-sectional study of data from the International Study Group of Pediatric Pancreatitis: In Search for a Cure, a registry of children with acute recurrent pancreatitis and chronic pancreatitis. Between-group differences were compared using Wilcoxon rank-sum test. Among 170 subjects in the registry, 76 (45%) had chronic pancreatitis; 57% were female, 80% were white; median age at diagnosis was 9.9 years. Pancreatitis-predisposing genetic mutations were identified in 51 (67%) and obstructive risk factors in 25 (33%). Toxic/metabolic and autoimmune factors were uncommon. Imaging demonstrated ductal abnormalities and pancreatic atrophy more commonly than calcifications. Fifty-nine (77%) reported abdominal pain within the past year; pain was reported as constant and receiving narcotics in 28%. Children with chronic pancreatitis reported a median of 3 emergency department visits and 2 hospitalizations in the last year. Forty-seven subjects (70%) missed 1 day of school in the past month as the result of chronic pancreatitis; 26 (34%) missed 3 or more days. Children reporting constant pain were more likely to miss school (P = .002), visit the emergency department (P = .01), and experience hospitalizations (P = .03) compared with children with episodic pain. Thirty-three children (43%) underwent therapeutic endoscopic retrograde pancreatography; one or more pancreatic surgeries were performed in 30 (39%). Chronic pancreatitis occurs at a young age with distinct clinical features. Genetic and obstructive risk factors are common, and disease burden is substantial. Copyright © 2015 Elsevier Inc. All rights reserved.

Prediction of Adulthood Obesity Using Genetic and Childhood Clinical Risk Factors in the Cardiovascular Risk in Young Finns Study.

Science.gov (United States)

Seyednasrollah, Fatemeh; Mäkelä, Johanna; Pitkänen, Niina; Juonala, Markus; Hutri-Kähönen, Nina; Lehtimäki, Terho; Viikari, Jorma; Kelly, Tanika; Li, Changwei; Bazzano, Lydia; Elo, Laura L; Raitakari, Olli T

2017-06-01

Obesity is a known risk factor for cardiovascular disease. Early prediction of obesity is essential for prevention. The aim of this study is to assess the use of childhood clinical factors and the genetic risk factors in predicting adulthood obesity using machine learning methods. A total of 2262 participants from the Cardiovascular Risk in YFS (Young Finns Study) were followed up from childhood (age 3-18 years) to adulthood for 31 years. The data were divided into training (n=1625) and validation (n=637) set. The effect of known genetic risk factors (97 single-nucleotide polymorphisms) was investigated as a weighted genetic risk score of all 97 single-nucleotide polymorphisms (WGRS97) or a subset of 19 most significant single-nucleotide polymorphisms (WGRS19) using boosting machine learning technique. WGRS97 and WGRS19 were validated using external data (n=369) from BHS (Bogalusa Heart Study). WGRS19 improved the accuracy of predicting adulthood obesity in training (area under the curve [AUC=0.787 versus AUC=0.744, P obesity. Predictive accuracy is highest among young children (3-6 years), whereas among older children (9-18 years) the risk can be identified using childhood clinical factors. The model is helpful in screening children with high risk of developing obesity. © 2017 American Heart Association, Inc.

Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

Science.gov (United States)

Miller, F W; Chen, W; O'Hanlon, T P; Cooper, R G; Vencovsky, J; Rider, L G; Danko, K; Wedderburn, L R; Lundberg, I E; Pachman, L M; Reed, A M; Ytterberg, S R; Padyukov, L; Selva-O'Callaghan, A; Radstake, T R; Isenberg, D A; Chinoy, H; Ollier, W E R; Scheet, P; Peng, B; Lee, A; Byun, J; Lamb, J A; Gregersen, P K; Amos, C I

2015-10-01

Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (Pmyositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with schizophrenia

Directory of Open Access Journals (Sweden)

Kadasah S

2017-04-01

Full Text Available Saeed Kadasah,1 Misbahul Arfin,2 Sadaf Rizvi,2 Mohammed Al-Asmari,2 Abdulrahman Al-Asmari2 1Department of Psychiatry, 2Division of Molecular Biology & Genetics, Scientific Research Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia Background: Schizophrenia is one of the most common devastating psychiatric disorders that negatively affects the quality of life and psychosocial functions. Its etiology involves the interplay of complex polygenic influences and environmental risk factors. Inflammatory markers are well-known etiological factors for psychiatric disorders, including schizophrenia. Objective: The aim of this study was to investigate the association of proinflammatory cytokine genes, tumor necrosis factor (TNF-α (-308G/A and TNF-β (+252A/G polymorphisms with schizophrenia susceptibility. Subjects and methods: TNF-α and TNF-β genes were amplified using amplification refractory mutation system primers in 180 schizophrenia patients and 200 healthy matched controls recruited from the Psychiatry Clinic of Prince Sultan Military Medical City, Riyadh. The frequencies of alleles and genotypes of TNF-α (-308G/A and TNF-β (+252A/G polymorphisms in patients were compared with those in controls. Results: The frequencies of TNF-α (-308 allele A and genotype GA were significantly higher, while those of allele G and genotype GG were lower in schizophrenia patients as compared to controls, indicating that genotype GA and allele A of TNF-α (-308G/A may increase susceptibility to schizophrenia, while genotype GG and allele G may reduce it. On the other hand, the distribution of alleles and genotypes of TNF-β (+252A/G polymorphism does not differ significantly in patients from controls; however, the frequency of genotype GG of TNF-β (+252A/G was significantly higher in male patients than in female patients. The distribution of TNF-α (-308G/A and TNF-β (+252A/G polymorphisms was almost similar in schizophrenia patients with

Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

NARCIS (Netherlands)

S. Reppe (Sjur); Y. Wang (Yunpeng); W.K. Thompson (Wesley K.); L.K. McEvoy (Linda K.); N.J. Schork (Nicholas); V. Zuber (Verena); M. Leblanc (Marissa); F. Bettella (Francesco); I.G. Mills (Ian G.); R.S. Desikan (Rahul S.); S. Djurovic (Srdjan); K.M. Gautvik (Kaare); A.M. Dale (Anders); O.A. Andreassen (Ole); K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James F); V. Aalto (Ville); M. Alen (Markku); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. Lacroix (Andrea Z.); S.H. Lee (Seung Hun); P.C. Leung (Ping C.); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); J. Woo (Jean); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William D.); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E. Slagboom (Eline); N.L.S. Tang (Nelson L.S.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S.T. Palsson (Stefan Th); J.I. Rotter (Jerome I.); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S.R. Cummings (Steven R.); P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K.T. Khaw; T. Lehtimäki (Terho); Y. Liu (YongMei); M. Lorentzon (Mattias); E. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huib); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak Chung); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cornelia); N.J. Wareham (Nicholas J.); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara B.); A.W.C. Kung (Annie Wai Chee); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John P.A.); D.P. Kiel (Douglas P.); F. Rivadeneira Ramirez (Fernando)

2015-01-01

textabstractBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown.

Chronic radiation exposure as an ecological factor: Hypermethylation and genetic differentiation in irradiated Scots pine populations

International Nuclear Information System (INIS)

Volkova, P.Yu.; Geras'kin, S.A.; Horemans, N.; Makarenko, E.S.; Saenen, E.; Duarte, G.T.; Nauts, R.; Bondarenko, V.S.; Jacobs, G.; Voorspoels, S.; Kudin, M.

2018-01-01

Genetic and epigenetic changes were investigated in chronically irradiated Scots pine (Pinus sylvestris L.) populations from territories that were heavily contaminated by radionuclides as result of the Chernobyl Nuclear Power Plant accident. In comparison to the reference site, the genetic diversity revealed by electrophoretic mobility of AFLPs was found to be significantly higher at the radioactively contaminated areas. In addition, the genome of pine trees was significantly hypermethylated at 4 of the 7 affected sites. - Highlights: • Chronic radiation exposure changes the genetic structure of plant populations. • Genomes of irradiated pines are hypermethylated. • The level of hypermethylation does not depend on annual dose. - These results indicate that even relatively low levels of chronic radiation exposure can influence on the genetic characteristics and the methylation status of natural pine populations and that it should be considered as an important ecological factor reflecting the anthropogenic impact on ecosystems.

Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder.

Science.gov (United States)

Sun, Xiao; Wu, Zhaomin; Cao, Qingjiu; Qian, Ying; Liu, Yong; Yang, Binrang; Chang, Suhua; Yang, Li; Wang, Yufeng

2018-05-16

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

[Parkinson's disease(s): recent insight into genetic factors

NARCIS (Netherlands)

Warrenburg, B.P.C. van de; Scheffer, H.; Heutink, P.; Bloem, B.R.

2007-01-01

In recent years, 5 genes have been identified that are unambiguously associated with genetic forms of Parkinson's disease. These genes probably explain less than 10% of all cases of Parkinson's disease. Clinically, these genetic forms can closely resemble idiopathic Parkinson's disease. Mutation

Genetic and modifying factors that determine the risk of brain tumors

DEFF Research Database (Denmark)

Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

2011-01-01

of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed...

Hypothesis: Genetic and epigenetic risk factors interact to modulate vulnerability and resilience to FASD

Directory of Open Access Journals (Sweden)

Elif eTunc-Ozcan

2014-08-01

Full Text Available Fetal alcohol spectrum disorder (FASD presents a collection of symptoms representing physiological and behavioral phenotypes caused by maternal alcohol consumption. Symptom severity is modified by genetic differences in fetal susceptibility and resistance as well as maternal genetic factors such as maternal alcohol sensitivity. Animal models demonstrate that both maternal and paternal genetics contribute to the variation in the fetus’ vulnerability to alcohol exposure. Maternal and paternal genetics define the variations in these phenotypes even without the effect of alcohol in utero, as most of these traits are polygenic, non-Mendelian, in their inheritance. In addition, the epigenetic alterations that instigate the alcohol induced neurodevelopmental deficits can interact with the polygenic inheritance of respective traits. Here, based on specific examples, we present the hypothesis that the principles of non-Mendelian inheritance, or ‘exceptions’ to Mendelian genetics, can be the driving force behind the severity of the prenatal alcohol-exposed individual’s symptomology. One such exception is when maternal alleles lead to an altered intrauterine hormonal environment and, therefore, produce variations in the long-term consequences on the development of the alcohol-exposed fetus. Another exception is when epigenetic regulation of allele-specific gene expression generates disequilibrium between the maternal versus paternal genetic contributions, and thereby, modifies the effect of prenatal alcohol exposure on the fetus. We propose that these situations in which one parent has an exaggerated influence over the offspring’s vulnerability to prenatal alcohol are major contributing mechanisms responsible for the variations in the symptomology of FASD in the exposed generation and beyond.

Genetics of osteoarthritis.

Science.gov (United States)

Rodriguez-Fontenla, Cristina; Gonzalez, Antonio

2015-01-01

Osteoarthritis (OA) is a complex disease caused by the interaction of multiple genetic and environmental factors. This review focuses on the studies that have contributed to the discovery of genetic susceptibility factors in OA. The most relevant associations discovered until now are discussed in detail: GDF-5, 7q22 locus, MCF2L, DOT1L, NCOA3 and also some important findings from the arcOGEN study. Moreover, the different approaches that can be used to minimize the specific problems of the study of OA genetics are discussed. These include the study of microsatellites, phenotype standardization and other methods such as meta-analysis of GWAS and gene-based analysis. It is expected that these new approaches contribute to finding new susceptibility genetic factors for OA. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

Use of a twin dataset to identify AMD-related visual patterns controlled by genetic factors

Science.gov (United States)

Quellec, Gwénolé; Abràmoff, Michael D.; Russell, Stephen R.

2010-03-01

The mapping of genotype to the phenotype of age-related macular degeneration (AMD) is expected to improve the diagnosis and treatment of the disease in a near future. In this study, we focused on the first step to discover this mapping: we identified visual patterns related to AMD which seem to be controlled by genetic factors, without explicitly relating them to the genes. For this purpose, we used a dataset of eye fundus photographs from 74 twin pairs, either monozygotic twins, who have the same genotype, or dizygotic twins, whose genes responsible for AMD are less likely to be identical. If we are able to differentiate monozygotic twins from dizygotic twins, based on a given visual pattern, then this pattern is likely to be controlled by genetic factors. The main visible consequence of AMD is the apparition of drusen between the retinal pigment epithelium and Bruch's membrane. We developed two automated drusen detectors based on the wavelet transform: a shape-based detector for hard drusen, and a texture- and color- based detector for soft drusen. Forty visual features were evaluated at the location of the automatically detected drusen. These features characterize the texture, the shape, the color, the spatial distribution, or the amount of drusen. A distance measure between twin pairs was defined for each visual feature; a smaller distance should be measured between monozygotic twins for visual features controlled by genetic factors. The predictions of several visual features (75.7% accuracy) are comparable or better than the predictions of human experts.

Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension

Czech Academy of Sciences Publication Activity Database

Pravenec, Michal; Zídek, Václav; Šimáková, Miroslava; Křen, Vladimír; Křenová, D.; Horký, K.; Jáchymová, M.; Míková, B.; Kazdová, L.; Aitman, T. J.; Churchill, P. C.; Webb, R. C.; Hingarh, N. H.; Yang, Y.; Wang, J. M.; St.Lezin, E. M.; Kurtz, W. T.

1999-01-01

Roč. 103, č. 12 (1999), s. 1651-1657 ISSN 0021-9738 R&D Projects: GA ČR GA306/97/0521; GA ČR GV204/98/K015 Grant - others:NIH(US) ROI HL-56028; NIH(US) PO1 HL-35018; NIH(US) HL-18575 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 * cardiovascular risk factors * spontaneous hypertension Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.921, year: 1999

Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

DEFF Research Database (Denmark)

Steffens, M.; Leu, C.; Ruppert, A. K.

2012-01-01

Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3 and account for 2030 of all epilepsies. Despite their high heritability of 80, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a ...

Shared Genetic Aetiology between Cognitive Ability and Cardiovascular Disease Risk Factors: Generation Scotland's Scottish Family Health Study

Science.gov (United States)

Luciano, Michelle; Batty, G. David; McGilchrist, Mark; Linksted, Pamela; Fitzpatrick, Bridie; Jackson, Cathy; Pattie, Alison; Dominiczak, Anna F.; Morris, Andrew D.; Smith, Blair H.; Porteous, David; Deary, Ian J.

2010-01-01

People with higher general cognitive ability in early life have more favourable levels of cardiovascular disease (CVD) risk factors in adulthood and CVD itself. The mechanism of these associations is not known. Here we examine whether general cognitive ability and CVD risk factors share genetic and/or environmental aetiology. In this large,…

What Froze the Genetic Code?

Directory of Open Access Journals (Sweden)

Lluís Ribas de Pouplana

2017-04-01

Full Text Available The frozen accident theory of the Genetic Code was a proposal by Francis Crick that attempted to explain the universal nature of the Genetic Code and the fact that it only contains information for twenty amino acids. Fifty years later, it is clear that variations to the universal Genetic Code exist in nature and that translation is not limited to twenty amino acids. However, given the astonishing diversity of life on earth, and the extended evolutionary time that has taken place since the emergence of the extant Genetic Code, the idea that the translation apparatus is for the most part immobile remains true. Here, we will offer a potential explanation to the reason why the code has remained mostly stable for over three billion years, and discuss some of the mechanisms that allow species to overcome the intrinsic functional limitations of the protein synthesis machinery.

What Froze the Genetic Code?

Science.gov (United States)

Ribas de Pouplana, Lluís; Torres, Adrian Gabriel; Rafels-Ybern, Àlbert

2017-04-05

The frozen accident theory of the Genetic Code was a proposal by Francis Crick that attempted to explain the universal nature of the Genetic Code and the fact that it only contains information for twenty amino acids. Fifty years later, it is clear that variations to the universal Genetic Code exist in nature and that translation is not limited to twenty amino acids. However, given the astonishing diversity of life on earth, and the extended evolutionary time that has taken place since the emergence of the extant Genetic Code, the idea that the translation apparatus is for the most part immobile remains true. Here, we will offer a potential explanation to the reason why the code has remained mostly stable for over three billion years, and discuss some of the mechanisms that allow species to overcome the intrinsic functional limitations of the protein synthesis machinery.

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

Mapping genetic factors controlling potato - cyst nematode interactions

NARCIS (Netherlands)

Rouppe van der Voort, J.N.A.M.

1998-01-01

The thesis describes strategies for genetic mapping of the genomes of the potato cyst nematode and potato. Mapping in cyst nematodes was achieved by AFLP genotyping of single cysts and subsequent segregation analysis in a family of sibling populations. The genetic map of Globodera