Assessing Extinction Risk: Integrating Genetic Information
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Jason Dunham
1999-06-01
Full Text Available Risks of population extinction have been estimated using a variety of methods incorporating information from different spatial and temporal scales. We briefly consider how several broad classes of extinction risk assessments, including population viability analysis, incidence functions, and ranking methods integrate information on different temporal and spatial scales. In many circumstances, data from surveys of neutral genetic variability within, and among, populations can provide information useful for assessing extinction risk. Patterns of genetic variability resulting from past and present ecological and demographic events, can indicate risks of extinction that are otherwise difficult to infer from ecological and demographic analyses alone. We provide examples of how patterns of neutral genetic variability, both within, and among populations, can be used to corroborate and complement extinction risk assessments.
Genetic cancer risk assessment in practice
International Nuclear Information System (INIS)
Gruber, S.
2004-01-01
The advent of genetic testing has made a dramatic impact on the management of individuals with inherited susceptibility to cancer and their relatives. Genetic counsel ing, with or without testing, is warranted when clues to familial cancer are recognized. Today, genetic testing for classic cancer genetic syndromes is now the standard of care, and has been complemented by genetic testing for other situations commonly encountered in clinical practice. Genetic testing for colorectal cancer, breast cancer, kidney cancer, thyroid cancer, melanoma, and pancreatic cancer raise important issues about the parameters for testing. Genetic cancer risk assessment can lead to measurable reductions in morbidity and mortality through strategies that rely on surveillance, chemo prevention, and risk-reducing surgery
Ecological Risk Assessment of Genetically Modified Higher Plants (GMHP)
DEFF Research Database (Denmark)
Kjær, C.; Damgaard, C.; Kjellsson, G.
Preface This publication is a first version of a manual identifying the data needs for ecological risk assessment of genetically modified higher plants (GMHP). It is the intention of the authors to stimulate further discussion of what data are needed in order to conduct a proper ecological risk...... of the project Biotechnology: elements in environmental risk assessment of genetically modified plants. December 1999 Christian Kjær Introduction In ecological risk assessment of transgenic plants, information on a wide range of subjects is needed for an effective and reliable assessment procedure...... in the amendment to the directive. This report suggests a structured way to identify the type of data needed to perform a sound ecological risk assessment for genetically modified higher plants (GMHP). The identified data types are intended to support the evaluation of the following risks: risk of invasion...
Risk Assessment of Genetically Modified Microorganisms
DEFF Research Database (Denmark)
Jacobsen, B. L.; Wilcks, Andrea
2001-01-01
the industry, national administration and research institutions were gathered to discuss which elements should be considered in a risk assessment of genetically modified microorganisms used as food or food ingredients. The existing EU and national regulations were presented, together with the experiences......The rapid development of recombinant DNA techniques for food organisms urges for an ongoing discussion on the risk assessment of both new as traditional use of microorganisms in food production. This report, supported by the Nordic Council of Ministers, is the result of a workshop where people from...... with risk assessment of these organisms in each Nordic country....
Cancer Genetics Risk Assessment and Counseling (PDQ®)—Health Professional Version
Cancer genetics risk assessment and genetic counseling includes family history, psychosocial assessments, and education on hereditary cancer syndromes, testing, and risk. Get more information including the ethical, legal, and social implications of genetic testing in this summary for clinicians.
Assessment of genetic risk for human exposure to radiation
International Nuclear Information System (INIS)
Sevcenko, V.A.; Rubanovic, A.V.
2002-01-01
Full text: The methodology of assessing the genetic risk of radiation exposure is based on the concept of 'hitting the target' in development of which N.V. Timofeeff-Ressovsky has played and important role. To predict genetic risk posed by irradiation, the U N Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) has worked out direct and indirect methods of assessment, extrapolation, integral and palpitation criteria of risk analysis that together permit calculating the risk from human exposure on the basis of data obtained for mice. Based on the reports of UNSCEAR for the period from 1958 to 2001 the paper presents a retrospective analysis of the use of direct methods and the doubling dose method for quantitative determination of the genetic risk of human exposure expressed as different hereditary diseases. As early as 1962 UNSCEAR estimated the doubling dose (a dose causing as many mutations as those occurring spontaneously during one generation) at 1 Gy for cases of exposure to ionizing radiations with low LET at a low dose rate and this value was confirmed in the next UNSCEAR reports up to now. For cases of acute irradiation the doubling dose was estimated at 0,3-0,4 Gy for the period under review. The paper considers the evolution of the concepts of human natural hereditary variability which is a basis for assessing the risk of exposure by the doubling dose method. The level of human natural genetic variability per 1 000 000 newborns is estimated at 738 000 hereditary diseases including mendelian, chromosomal and multifactorial ones. The greatest difficulties in assessing the doubling dose value were found to occur in the case of multifactorial diseases the pheno typical expression of which depends on mutational events in polygenic systems and on numerous environmental factors. The introduction in calculations of the potential recoverability correction factor (RPCF) made it possible to assess the genetic risk taking into account this class of
Computerised Genetic Risk Assessment and Decision Support in Primary Care
Directory of Open Access Journals (Sweden)
Andrew Coulson
2000-09-01
To address these issues, a new computer application called RAGs (Risk Assessment in Genetics has been designed. The system allows a doctor to create family trees and assess genetic risk of breast cancer. RAGs possesses two features that distinguish it from similar software: (a a user-centred design, which takes into account the requirements of the doctor-patient encounter; (b risk reporting using qualitative evidence for or against an increased risk, which the authors believe to be more useful and accessible than numerical probabilities are. In that the system allows for any genetic risk guideline to be implemented, it can be used with all diseases for which evaluation guidelines exist. The software may be easily modified to cater for the amount of detail required by different specialists.
Guidance on the environmental risk assessment of genetically modified plants
DEFF Research Database (Denmark)
Bartsch, Detlef; Chueca, Cristina; De-Schrijver, Adinda
risk evaluation. The scientific Panel on Genetically Modified Organisms (of the European Food Safety Authority (EFSA GMO Panel) considers seven specific areas of concern to be addressed by applicants and risk assessors during the ERA (1) persistence and invasiveness of the GM plant , or its compatible......This document provides guidance for the environmental risk assessment (ERA) of genetically modified (GM) plants submitted within the framework of Regulation (EC) No. 1829/2003 on GM food and feed or under Directive 2001/18/EC on the deliberate release into the environment of genetically modified...... organisms (GMOs). This document provides guidance for assessing potential effects of GM plants on the environment and the rationales for the data requirements for a comprehensive ERA of GM plants. The ERA should be carried out on a case-by-case basis, following a step-by-step assessment approach...
Assessment of genetic risk for human exposure to radiation. State of the art
International Nuclear Information System (INIS)
Shevchenko, V.A.
2000-01-01
Historical aspects of the conception of genetic risk of human irradiation for recent 40 years. Methodology of assessing the genetic risk of radiation exposure is based on the concept of hitting the target. To predict genetic risk of irradiation, the direct and indirect methods of assessment, extrapolation, integral and populational criteria of risk analysis is widely used. Combination of these methods permits to calculate the risk from human exposure on the basis of data obtained for mice. Method of doubling dose based on determination of the dose doubling the level of natural mutational process in humans is the main one used to predict the genetic risk. Till 1972 the main model for assessing the genetic risk was the human/mouse model (the use of data on the spontaneous human variability and data on the frequency of induced mutations in mice). In the period from 1972 till 1994 the mouse/mouse model was intensively elaborated in many laboratories. This model was also used in this period to analyse the genetic risk of human irradiation. Recent achievements associated with the study of molecular nature of many hereditary human diseases as well as the criticism of a fundamental principles of the mouse/mouse model for estimating the genetic risk on a new basis. Estimates of risk for the different classes of genetic diseases have been obtained using the doubling-dose method [ru
Biodiversity analyses for risk assessment of genetically modified potato
Lazebnik, Jenny; Dicke, Marcel; Braak, ter Cajo J.F.; Loon, van Joop J.A.
2017-01-01
An environmental risk assessment for the introduction of genetically modified crops includes assessing the consequences for biodiversity. In this study arthropod biodiversity was measured using pitfall traps in potato agro-ecosystems in Ireland and The Netherlands over two years. We tested the
Assessing the impact of a combined analysis of four common low-risk genetic variants on autism risk
Directory of Open Access Journals (Sweden)
Carayol Jerome
2010-02-01
Full Text Available Abstract Background Autism is a complex disorder characterized by deficits involving communication, social interaction, and repetitive and restrictive patterns of behavior. Twin studies have shown that autism is strongly heritable, suggesting a strong genetic component. In other disease states with a complex etiology, such as type 2 diabetes, cancer and cardiovascular disease, combined analysis of multiple genetic variants in a genetic score has helped to identify individuals at high risk of disease. Genetic scores are designed to test for association of genetic markers with disease. Method The accumulation of multiple risk alleles markedly increases the risk of being affected, and compared with studying polymorphisms individually, it improves the identification of subgroups of individuals at greater risk. In the present study, we show that this approach can be applied to autism by specifically looking at a high-risk population of children who have siblings with autism. A two-sample study design and the generation of a genetic score using multiple independent genes were used to assess the risk of autism in a high-risk population. Results In both samples, odds ratios (ORs increased significantly as a function of the number of risk alleles, with a genetic score of 8 being associated with an OR of 5.54 (95% confidence interval [CI] 2.45 to 12.49. The sensitivities and specificities for each genetic score were similar in both analyses, and the resultant area under the receiver operating characteristic curves were identical (0.59. Conclusions These results suggest that the accumulation of multiple risk alleles in a genetic score is a useful strategy for assessing the risk of autism in siblings of affected individuals, and may be better than studying single polymorphisms for identifying subgroups of individuals with significantly greater risk.
Risk assessment: the importance of genetic polymorphisms in man
DEFF Research Database (Denmark)
Knudsen, Lisbeth E.; Loft, S H; Autrup, H
2001-01-01
and increased cancer risk, such results indicate effect modification regarding cancer risk. In risk assessment the safety 'factor' of 10 is generally accepted to allow for variation in individual susceptibility. Reviewing the literature justifies the factor of 10 when considering single polymorphisms. However......Many genetic polymorphisms in metabolism enzymes are important for the risk of cancer as shown in a large number of case-control studies. The relative risk estimates have shown large variations between such population studies. However, in most studies the relative risk estimates are in the range...
Assessing individual risk for AMD with genetic counseling, family history, and genetic testing.
Cascella, R; Strafella, C; Longo, G; Manzo, L; Ragazzo, M; De Felici, C; Gambardella, S; Marsella, L T; Novelli, G; Borgiani, P; Sangiuolo, F; Cusumano, A; Ricci, F; Giardina, E
2018-02-01
PurposeThe goal was to develop a simple model for predicting the individual risk profile for age-related macular degeneration (AMD) on the basis of genetic information, disease family history, and smoking habits.Patients and methodsThe study enrolled 151 AMD patients following specific clinical and environmental inclusion criteria: age >55 years, positive family history for AMD, presence of at least one first-degree relative affected by AMD, and smoking habits. All of the samples were genotyped for rs1061170 (CFH) and rs10490924 (ARMS2) with a TaqMan assay, using a 7500 Fast Real Time PCR device. Statistical analysis was subsequently employed to calculate the real individual risk (OR) based on the genetic data (ORgn), family history (ORf), and smoking habits (ORsm).Results and conclusionThe combination of ORgn, ORf, and ORsm allowed the calculation of the Ort that represented the realistic individual risk for developing AMD. In this report, we present a computational model for the estimation of the individual risk for AMD. Moreover, we show that the average distribution of risk alleles in the general population and the knowledge of parents' genotype can be decisive to assess the real disease risk. In this contest, genetic counseling is crucial to provide the patients with an understanding of their individual risk and the availability for preventive actions.
A genetic fuzzy system for unstable angina risk assessment.
Dong, Wei; Huang, Zhengxing; Ji, Lei; Duan, Huilong
2014-02-18
Unstable Angina (UA) is widely accepted as a critical phase of coronary heart disease with patients exhibiting widely varying risks. Early risk assessment of UA is at the center of the management program, which allows physicians to categorize patients according to the clinical characteristics and stratification of risk and different prognosis. Although many prognostic models have been widely used for UA risk assessment in clinical practice, a number of studies have highlighted possible shortcomings. One serious drawback is that existing models lack the ability to deal with the intrinsic uncertainty about the variables utilized. In order to help physicians refine knowledge for the stratification of UA risk with respect to vagueness in information, this paper develops an intelligent system combining genetic algorithm and fuzzy association rule mining. In detail, it models the input information's vagueness through fuzzy sets, and then applies a genetic fuzzy system on the acquired fuzzy sets to extract the fuzzy rule set for the problem of UA risk assessment. The proposed system is evaluated using a real data-set collected from the cardiology department of a Chinese hospital, which consists of 54 patient cases. 9 numerical patient features and 17 categorical patient features that appear in the data-set are selected in the experiments. The proposed system made the same decisions as the physician in 46 (out of a total of 54) tested cases (85.2%). By comparing the results that are obtained through the proposed system with those resulting from the physician's decision, it has been found that the developed model is highly reflective of reality. The proposed system could be used for educational purposes, and with further improvements, could assist and guide young physicians in their daily work.
Rajan, S Ravi; Letourneau, Deborah K
2012-01-01
The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large.
Directory of Open Access Journals (Sweden)
S. Ravi Rajan
2012-01-01
Full Text Available The risks of genetically modified organisms (GMOs are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large.
White, Paul A; Johnson, George E
2016-05-01
Applied genetic toxicology is undergoing a transition from qualitative hazard identification to quantitative dose-response analysis and risk assessment. To facilitate this change, the Health and Environmental Sciences Institute (HESI) Genetic Toxicology Technical Committee (GTTC) sponsored a workshop held in Lancaster, UK on July 10-11, 2014. The event included invited speakers from several institutions and the contents was divided into three themes-1: Point-of-departure Metrics for Quantitative Dose-Response Analysis in Genetic Toxicology; 2: Measurement and Estimation of Exposures for Better Extrapolation to Humans and 3: The Use of Quantitative Approaches in Genetic Toxicology for human health risk assessment (HHRA). A host of pertinent issues were discussed relating to the use of in vitro and in vivo dose-response data, the development of methods for in vitro to in vivo extrapolation and approaches to use in vivo dose-response data to determine human exposure limits for regulatory evaluations and decision-making. This Special Issue, which was inspired by the workshop, contains a series of papers that collectively address topics related to the aforementioned themes. The Issue includes contributions that collectively evaluate, describe and discuss in silico, in vitro, in vivo and statistical approaches that are facilitating the shift from qualitative hazard evaluation to quantitative risk assessment. The use and application of the benchmark dose approach was a central theme in many of the workshop presentations and discussions, and the Special Issue includes several contributions that outline novel applications for the analysis and interpretation of genetic toxicity data. Although the contents of the Special Issue constitutes an important step towards the adoption of quantitative methods for regulatory assessment of genetic toxicity, formal acceptance of quantitative methods for HHRA and regulatory decision-making will require consensus regarding the
The relevance of animal experimental results for the assessment of radiation genetic risks in man
International Nuclear Information System (INIS)
Stephan, G.
1981-01-01
No suitable data are available from man for the quantitative assessment of genetic radiation risk. Therefore, the results from experiments on animals must be utilized. Two hypotheses are presented here in drawing analogical conclusions from one species to another. Although the extrapolation of results from animal experiments remains an open question, the use of experimental results from mice seems to be justified for an assessment of the genetic radiation risk in man. (orig.) [de
Directory of Open Access Journals (Sweden)
Beth Anderson
2012-01-01
Full Text Available Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS. Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%. One hundred twenty-two (42.2% reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.
International Nuclear Information System (INIS)
Anderson, B.; McLosky, J.; Wasilevich, E.; Callo, S. L.; Duquette, D.; Copeland, G.
2012-01-01
Introduction. Women diagnosed with breast cancer at a young age are more likely to carry a cancer predisposing genetic mutation. Per the current NCCN recommendations, women diagnosed under age 50 should be referred to cancer genetic counseling for further risk evaluation. This study seeks to assess patient-reported barriers and facilitators to receiving genetic counseling and risk assessment among a community-based population of young breast cancer survivors (YBCS). Methods. Through the Michigan Cancer Surveillance Program, a state-based cancer registry, 488 women diagnosed with breast cancer before age 50 in 2006-2007 were identified. They received a mail survey regarding family history and facilitators and barriers to receiving genetic counseling and risk assessment. Results. Responses were received from 289 women (59.2%). One hundred twenty-two (42.2%) reported having received cancer genetic counseling. The most frequent reason identified for receiving services was to benefit their family's future. The top reasons for not attending were “no one recommended it” and “medical insurance coverage issues.” Discussion. This study is the first published report using a state cancer registry to determine facilitators and barriers to receiving genetic counseling and risk assessment among YBCS. These findings demonstrate the need for additional awareness and education about appropriate indications for genetic services.
DTREEv2, a computer-based support system for the risk assessment of genetically modified plants
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
Directory of Open Access Journals (Sweden)
Benjamin A Goldstein
2014-08-01
Full Text Available Purpose: Genetic risk assessment is becoming an important component of clinical decision-making. Genetic Risk Scores (GRSs allow the composite assessment of genetic risk in complex traits. A technically and clinically pertinent question is how to most easily and effectively combine a GRS with an assessment of clinical risk derived from established non-genetic risk factors as well as to clearly present this information to patient and health care providers. Materials & Methods: We illustrate a means to combine a GRS with an independent assessment of clinical risk using a log-link function. We apply the method to the prediction of coronary heart disease (CHD in the Atherosclerosis Risk in Communities (ARIC cohort. We evaluate different constructions based on metrics of effect change, discrimination, and calibration.Results: The addition of a GRS to a clinical risk score (CRS improves both discrimination and calibration for CHD in ARIC. Results are similar regardless of whether external vs. internal coefficients are used for the CRS, risk factor SNPs are included in the GRS, or subjects with diabetes at baseline are excluded. We outline how to report the construction and the performance of a GRS using our method and illustrate a means to present genetic risk information to subjects and/or their health care provider. Conclusion: The proposed method facilitates the standardized incorporation of a GRS in risk assessment.
Calabrese, Edward J
2015-04-01
The Genetics Panel of the National Academy of Sciences' Committee on Biological Effects of Atomic Radiation (BEAR) recommended the adoption of the linear dose-response model in 1956, abandoning the threshold dose-response for genetic risk assessments. This recommendation was quickly generalized to include somatic cells for cancer risk assessment and later was instrumental in the adoption of linearity for carcinogen risk assessment by the Environmental Protection Agency. The Genetics Panel failed to provide any scientific assessment to support this recommendation and refused to do so when later challenged by other leading scientists. Thus, the linearity model used in cancer risk assessment was based on ideology rather than science and originated with the recommendation of the NAS BEAR Committee Genetics Panel. Historical documentation in support of these conclusions is provided in the transcripts of the Panel meetings and in previously unexamined correspondence among Panel members.
Sparrow, Penny A. C.
GM risk assessments play an important role in the decision-making process surrounding the regulation, notification and permission to handle Genetically Modified Organisms (GMOs). Ultimately the role of a GM risk assessment will be to ensure the safe handling and containment of the GMO; and to assess any potential impacts on the environment and human health. A risk assessment should answer all ‘what if’ scenarios, based on scientific evidence.
Assessing the evidence for shared genetic risks across psychiatric disorders and traits.
Martin, Joanna; Taylor, Mark J; Lichtenstein, Paul
2017-12-04
Genetic influences play a significant role in risk for psychiatric disorders, prompting numerous endeavors to further understand their underlying genetic architecture. In this paper, we summarize and review evidence from traditional twin studies and more recent genome-wide molecular genetic analyses regarding two important issues that have proven particularly informative for psychiatric genetic research. First, emerging results are beginning to suggest that genetic risk factors for some (but not all) clinically diagnosed psychiatric disorders or extreme manifestations of psychiatric traits in the population share genetic risks with quantitative variation in milder traits of the same disorder throughout the general population. Second, there is now evidence for substantial sharing of genetic risks across different psychiatric disorders. This extends to the level of characteristic traits throughout the population, with which some clinical disorders also share genetic risks. In this review, we summarize and evaluate the evidence for these two issues, for a range of psychiatric disorders. We then critically appraise putative interpretations regarding the potential meaning of genetic correlation across psychiatric phenotypes. We highlight several new methods and studies which are already using these insights into the genetic architecture of psychiatric disorders to gain additional understanding regarding the underlying biology of these disorders. We conclude by outlining opportunities for future research in this area.
The assessment of genetic risk of breast cancer : a set of GP guidelines
de Bock, GH; Vlieland, TPMV; Hageman, GCHA; Oosterwijk, JC; Springer, MP; Kievit, J
Background. Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to
International Nuclear Information System (INIS)
Côte, Jessica; Bouétard, Anthony; Pronost, Yannick; Besnard, Anne-Laure; Coke, Maïra; Piquet, Fabien; Caquet, Thierry; Coutellec, Marie-Agnès
2015-01-01
The use of standardized monospecific testing to assess the ecological risk of chemicals implicitly relies on the strong assumption that intraspecific variation in sensitivity is negligible or irrelevant in this context. In this study, we investigated genetic variation in copper sensitivity of the freshwater snail Lymnaea stagnalis, using lineages stemming from eight natural populations or strains found to be genetically differentiated at neutral markers. Copper-induced mortality varied widely among populations, as did the estimated daily death rate and time to 50% mortality (LT50). Population genetic divergence in copper sensitivity was compared to neutral differentiation using the Q ST -F ST approach. No evidence for homogenizing selection could be detected. This result demonstrates that species-level extrapolations from single population studies are highly unreliable. The study provides a simple example of how evolutionary principles could be incorporated into ecotoxicity testing in order to refine ecological risk assessment. - Highlights: • Genetic variation in copper tolerance occurs between Lymnaea stagnalis populations. • We used the Q ST -F ST approach to test evolutionary patterns in copper tolerance. • No evidence for uniform selection was found. • Results suggest that extrapolations to the species level are not safe. • A method is proposed to refine ecological risk assessment using genetic parameters. - Genetic variation in copper tolerance occurs in Lymnaea stagnalis. A method is proposed for considering evolutionary parameters in ecological risk assessment
Aguilera, Jaime; Gomes, Ana R; Olaru, Irina
2013-10-01
Genetically modified microorganisms (GMMs) are involved in the production of a variety of food and feed. The release and consumption of these products can raise questions about health and environmental safety. Therefore, the European Union has different legislative instruments in place in order to ensure the safety of such products. A key requirement is to conduct a scientific risk assessment as a prerequisite for the product to be placed on the market. This risk assessment is performed by the European Food Safety Authority (EFSA), through its Scientific Panels. The EFSA Panel on Genetically Modified Organisms has published complete and comprehensive guidance for the risk assessment of GMMs and their products for food and/or feed use, in which the strategy and the criteria to conduct the assessment are explained, as well as the scientific data to be provided in applications for regulated products. This Guidance follows the main risk assessment principles developed by various international organisations (Codex Alimentarius, 2003; OECD, 2010). The assessment considers two aspects: the characterisation of the GMM and the possible effects of its modification with respect to safety, and the safety of the product itself. Due to the existing diversity of GMMs and their products, a categorisation is recommended to optimise the assessment and to determine the extent of the required data. The assessment starts with a comprehensive characterisation of the GMM, covering the recipient/parental organism, the donor(s) of the genetic material, the genetic modification, and the final GMM and its phenotype. Evaluation of the composition, potential toxicity and/or allergenicity, nutritional value and environmental impact of the product constitute further cornerstones of the process. The outcome of the assessment is reflected in a scientific opinion which indicates whether the product raises any safety issues. This opinion is taken into account by the different European regulatory
Applying personal genetic data to injury risk assessment in athletes.
Directory of Open Access Journals (Sweden)
Gabrielle T Goodlin
Full Text Available Recent studies have identified genetic markers associated with risk for certain sports-related injuries and performance-related conditions, with the hope that these markers could be used by individual athletes to personalize their training and diet regimens. We found that we could greatly expand the knowledge base of sports genetic information by using published data originally found in health and disease studies. For example, the results from large genome-wide association studies for low bone mineral density in elderly women can be re-purposed for low bone mineral density in young endurance athletes. In total, we found 124 single-nucleotide polymorphisms associated with: anterior cruciate ligament tear, Achilles tendon injury, low bone mineral density and stress fracture, osteoarthritis, vitamin/mineral deficiencies, and sickle cell trait. Of these single nucleotide polymorphisms, 91% have not previously been used in sports genetics. We conducted a pilot program on fourteen triathletes using this expanded knowledge base of genetic variants associated with sports injury. These athletes were genotyped and educated about how their individual genetic make-up affected their personal risk profile during an hour-long personal consultation. Overall, participants were favorable of the program, found it informative, and most acted upon their genetic results. This pilot program shows that recent genetic research provides valuable information to help reduce sports injuries and to optimize nutrition. There are many genetic studies for health and disease that can be mined to provide useful information to athletes about their individual risk for relevant injuries.
Genetically Modified Foods: A Brief Overview of the Risk Assessment Process.
Finkelstein, Paige E
2016-02-18
Billions of people worldwide are unable to meet their daily micro nutritional needs. Genetically modified (GM) foods, while initially developed to tolerate herbicides and resist disease and insects, have the potential to help alleviate this issue that is currently posing a serious public health concern. However, there is a negative public perception surrounding GM foods, calling for more research regarding the risks that GM foods could pose to the public, specifically on the topics of allergenicity and gene transfer. The risk assessments of GM foods should be performed on a case-by-case basis, by a process outlined by the WHO. The goal of determining food safety is to obtain reasonable certainty that under normal levels of consumption, there will be no harm to people. Current research has shown that GM foods do not cause increased allergenicity or have a meaningful risk of gene transfer to people. GM foods should become publicly accepted products that can bring significant benefit to people at risk of under nutrition.
Genetic toxicology and cancer risk assessment
National Research Council Canada - National Science Library
Choy, Wai Nang
2001-01-01
... their risks to humans are obvious goals for the protection of public health. When exposure is unavoidable, an accurate estimation of human risk as a result of exposure is essential for making regulatory decisions. Quantitative cancer risk assessment is an intricate process that utilizes knowledge from many different scien...
Common Genetic Risk for Melanoma Encourages Preventive Behavior Change
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Lori Diseati
2015-02-01
Full Text Available There is currently great interest in using genetic risk estimates for common disease in personalized healthcare. Here we assess melanoma risk-related preventive behavioral change in the context of the Coriell Personalized Medicine Collaborative (CPMC. As part of on-going reporting activities within the project, participants received a personalized risk assessment including information related to their own self-reported family history of melanoma and a genetic risk variant showing a moderate effect size (1.7, 3.0 respectively for heterozygous and homozygous individuals. Participants who opted to view their report were sent an optional outcome survey assessing risk perception and behavioral change in the months that followed. Participants that report family history risk, genetic risk, or both risk factors for melanoma were significantly more likely to increase skin cancer preventive behaviors when compared to participants with neither risk factor (ORs = 2.04, 2.79, 4.06 and p-values = 0.02, 2.86 × 10−5, 4.67 × 10−5, respectively, and we found the relationship between risk information and behavior to be partially mediated by anxiety. Genomic risk assessments appear to encourage positive behavioral change in a manner that is complementary to family history risk information and therefore may represent a useful addition to standard of care for melanoma prevention.
The impact of the human genome project on risk assessment
International Nuclear Information System (INIS)
Katarzyna Doerffer; Paul Unrau.
1996-01-01
The radiation protection approach to risk assessment assumes that cancer induction following radiation exposure is purely random. Present risk assessment methods derive risk from cancer incidence frequencies in exposed populations and associate disease outcomes totally with the level of exposure to ionizing red aeon. Exposure defines a risk factor that affects the probability of the disease outcome. But cancer risk can be affected by other risk factors such as underlying genetic factors (predisposition) of the exposed organism. These genetic risk factors are now becoming available for incorporation into ionizing radiation risk assessment Progress in the Human Genome Project (HOP) will lead to direct assays to measure the effects of genetic risk determinants in disease outcomes. When all genetic risk determinants are known and incorporated into risk assessment it will be possible to reevaluate the role of ionizing radiation in the causation of cancer. (author)
Environmental impact assessment of genetically modified biocontrol agents
International Nuclear Information System (INIS)
Migheli, Q.
2001-01-01
This review summarises the theoretical basis of risk analysis, and the political and social implications of introducing new biotechnology products in agricultural environments. The main factors to be considered under the present European regulation in the environmental impact assessment of genetically modified biocontrol agents are briefly discussed. Finally, an alternative risk assessment paradigm is proposed for genetically modified microorganisms, which shall consider the intrinsic properties of each antagonist, rather than the method used for generating it [it
Do species conservation assessments capture genetic diversity?
Directory of Open Access Journals (Sweden)
Malin C. Rivers
2014-12-01
Full Text Available The best known system for classifying threat status of species, the IUCN Red List, currently lacks explicit considerations of genetic diversity, and consequently may not account for potential adaptation of species to future environmental change. To address this gap, we integrate range-wide genetic analysis with IUCN Red List assessments.We calculated the loss of genetic diversity under simulated range loss for species of Delonix (Leguminosae. Simulated range loss involved random loss of populations and was intended to model ongoing habitat destruction. We found a strong relationship between loss of genetic diversity and range. Moreover, we found correspondence between levels of genetic diversity and thresholds for ‘non-threatened’ versus ‘threatened’ IUCN Red List categories.Our results support the view that current threat thresholds of the IUCN Red List criteria reflect genetic diversity, and hence evolutionary potential; although the genetic diversity distinction between threatened categories was less evident. Thus, by supplementing conventional conservation assessments with genetic data, new insights into the biological robustness of IUCN Red List assessments for targeted conservation initiatives can be achieved. Keywords: Conservation assessment, Conservation genetics, Extinction risk, Genetic diversity, IUCN Red List, Range
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women
... their family history of cancer. Depending on a woman’s family history, the doctor or nurse may then use a ... against routine genetic counseling or BRCA testing of women whose family history is not associated with an increased risk for ...
International Nuclear Information System (INIS)
Mortensen, Holly M.; Euling, Susan Y.
2013-01-01
Response to environmental chemicals can vary widely among individuals and between population groups. In human health risk assessment, data on susceptibility can be utilized by deriving risk levels based on a study of a susceptible population and/or an uncertainty factor may be applied to account for the lack of information about susceptibility. Defining genetic susceptibility in response to environmental chemicals across human populations is an area of interest in the NAS' new paradigm of toxicity pathway-based risk assessment. Data from high-throughput/high content (HT/HC), including -omics (e.g., genomics, transcriptomics, proteomics, metabolomics) technologies, have been integral to the identification and characterization of drug target and disease loci, and have been successfully utilized to inform the mechanism of action for numerous environmental chemicals. Large-scale population genotyping studies may help to characterize levels of variability across human populations at identified target loci implicated in response to environmental chemicals. By combining mechanistic data for a given environmental chemical with next generation sequencing data that provides human population variation information, one can begin to characterize differential susceptibility due to genetic variability to environmental chemicals within and across genetically heterogeneous human populations. The integration of such data sources will be informative to human health risk assessment
Genetic Stratification in Myeloid Diseases: From Risk Assessment to Clinical Decision Support Tool
Directory of Open Access Journals (Sweden)
Yishai Ofran
2014-10-01
Full Text Available Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational studies may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequencing techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to becoming a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.
An overall genetic risk assessment for radiological protection purposes
International Nuclear Information System (INIS)
Oftedal, P.; Searle, A.G.
1980-01-01
Risks of serious hereditary damage in the first and second generations after low level radiation exposure and at equilibrium were calculated by using a doubling dose of 100 rem (based on experimental work with the mouse) and by considering separately the various categories of genic and chromosomal defect. Prenatal lethality was not included. It is estimated that after the exposure of a population of future parents to a collective dose of 1 million man-rem, about 125 extra cases of serious genetic ill health would appear in children and grandchildren. In all future generations, a total of about 320 cases is expected, provided the population remains of constant size. It is emphasised however, that a number of major assumptions have to be made in order to arrive at any overall genetic risk estimate, so that the confidence limits of these figures are bound to be wide. (author)
Structured parenting of toddlers at high versus low genetic risk: two pathways to child problems.
Leve, Leslie D; Harold, Gordon T; Ge, Xiaojia; Neiderhiser, Jenae M; Shaw, Daniel; Scaramella, Laura V; Reiss, David
2009-11-01
Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for psychopathology. The sample included 290 linked sets of adoptive families and birth mothers and 95 linked birth fathers. Genetic risk was assessed via birth mother and birth father psychopathology (anxiety, depression, antisociality, and drug use). Structured parenting was assessed via microsocial coding of adoptive mothers' behavior during a cleanup task. Toddler behavior problems were assessed with the Child Behavior Checklist. Controlling for temperamental risk at 9 months, there was an interaction between birth mother psychopathology and adoptive mothers' parenting on toddler behavior problems at 18 months. The interaction indicated two pathways to child problems: structured parenting was beneficial for toddlers at high genetic risk but was related to behavior problems for toddlers at low genetic risk. This crossover interaction pattern was replicated with birth father psychopathology as the index of genetic risk. The effects of structured parenting on toddler behavior problems varied as a function of genetic risk. Children at genetic risk might benefit from parenting interventions during toddlerhood that enhance structured parenting.
Fedy, Bradley C.; Row, Jeffery R.; Oyler-McCance, Sara J.
2017-01-01
The identification and demographic assessment of biologically meaningful populations is fundamental to species’ ecology and management. Although genetic tools are used frequently to identify populations, studies often do not incorporate demographic data to understand their respective population trends. We used genetic data to define subpopulations in a continuously distributed species. We assessed demographic independence and variation in population trends across the distribution. Additionally, we identified potential barriers to gene flow among subpopulations. We sampled greater sage-grouse (Centrocercus urophasianus) leks from across their range (≈175,000 Km2) in Wyoming and amplified DNA at 14 microsatellite loci for 1761 samples. Subsequently, we assessed population structure in unrelated individuals (n = 872) by integrating results from multiple Bayesian clustering approaches and used the boundaries to inform our assessment of long-term population trends and lek activity over the period of 1995–2013. We identified four genetic clusters of which two northern ones showed demographic independence from the others. Trends in population size for the northwest subpopulation were statistically different from the other three genetic clusters and the northeast and southwest subpopulations demonstrated a general trend of increasing proportion of inactive leks over time. Population change from 1996 to 2012 suggested population growth in the southern subpopulations and decline, or neutral, change in the northern subpopulations. We suggest that sage-grouse subpopulations in northern Wyoming are at greater risk of extirpation than the southern subpopulations due to smaller census and effective population sizes and higher variability within subpopulations. Our research is an example of incorporating genetic and demographic data and provides guidance on the identification of subpopulations of conservation concern.
Environmental Risk Assessment of Genetically Modified Organisms (GMOs)
DEFF Research Database (Denmark)
Strandberg, B.; Kjær, C.; Hindar, K.
It was the aim of this NordTest project to propose improvements that prepare us to assess ecological risks to the environment associated with releases of existing and coming GMO cases. The report is separated into three sections. The first describes the frames of ecological risk assessment...
Genetic risk score predicting risk of rheumatoid arthritis phenotypes and age of symptom onset.
Directory of Open Access Journals (Sweden)
Lori B Chibnik
Full Text Available Cumulative genetic profiles can help identify individuals at high-risk for developing RA. We examined the impact of 39 validated genetic risk alleles on the risk of RA phenotypes characterized by serologic and erosive status.We evaluated single nucleotide polymorphisms at 31 validated RA risk loci and 8 Human Leukocyte Antigen alleles among 542 Caucasian RA cases and 551 Caucasian controls from Nurses' Health Study and Nurses' Health Study II. We created a weighted genetic risk score (GRS and evaluated it as 7 ordinal groups using logistic regression (adjusting for age and smoking to assess the relationship between GRS group and odds of developing seronegative (RF- and CCP-, seropositive (RF+ or CCP+, erosive, and seropositive, erosive RA phenotypes. In separate case only analyses, we assessed the relationships between GRS and age of symptom onset. In 542 RA cases, 317 (58% were seropositive, 163 (30% had erosions and 105 (19% were seropositive with erosions. Comparing the highest GRS risk group to the median group, we found an OR of 1.2 (95% CI = 0.8-2.1 for seronegative RA, 3.0 (95% CI = 1.9-4.7 for seropositive RA, 3.2 (95% CI = 1.8-5.6 for erosive RA, and 7.6 (95% CI = 3.6-16.3 for seropositive, erosive RA. No significant relationship was seen between GRS and age of onset.Results suggest that seronegative and seropositive/erosive RA have different genetic architecture and support the importance of considering RA phenotypes in RA genetic studies.
Assessment of risk from radiation sources
International Nuclear Information System (INIS)
Subbaratnam, T.; Madhvanath, U.; Somasundaram, S.
1976-01-01
Assessment of risk from exposure to ionizing radiations from man-made radiation sources and nuclear installations has to be viewed from three aspects, namely, dose-effect relationship (genetic and somatic) for humans, calculation of doses or dose-commitments to population groups, assessment of risk to radiation workers and the population at large from the current levels of exposure from nuclear industry and comparison of risk estimates with other industries in a modern society. These aspects are discussed in brief. On the basis of available data, it is shown that estimated incidence of genetic diseases and cancers due to exposure of population to radiation from nuclear industry is negligible in comparison with their natural incidence, and radiation risks to the workers in nuclear industry are much lower than the risks in other occupations. (M.G.B.)
International Nuclear Information System (INIS)
Selby, P.B.
Two widely-recognized committees, UNSCEAR and BEIR, have reevaluated their estimates of genetic risks from radiation. Their estimates for gene mutations are based on two different approaches, one being the doubling-dose approach and the other being a new direct approach based on an empirical determination of the amount of dominant induced damage in the skeletons of mice in the first generation following irradiation. The estimates made by these committees are in reasonably good agreement and suggest that the genetic risks from present exposures resultng from nuclear power production are small. There is room for much improvement in the reliability of the risk estimates. The relatively new approach of measuring the amount of induced damage to the mouse skeleton shows great promise of improving knowledge about how changes in the mutation frequency affect the incidence of genetic disorders. Such findings may have considerable influence on genetic risk estimates for radiation and on the development of risk estimates for other less-well-understood environmental mutagens. (author)
Côte, Jessica; Bouétard, Anthony; Pronost, Yannick; Besnard, Anne-Laure; Coke, Maïra; Piquet, Fabien; Caquet, Thierry; Coutellec, Marie-Agnès
2015-10-01
The use of standardized monospecific testing to assess the ecological risk of chemicals implicitly relies on the strong assumption that intraspecific variation in sensitivity is negligible or irrelevant in this context. In this study, we investigated genetic variation in copper sensitivity of the freshwater snail Lymnaea stagnalis, using lineages stemming from eight natural populations or strains found to be genetically differentiated at neutral markers. Copper-induced mortality varied widely among populations, as did the estimated daily death rate and time to 50% mortality (LT50). Population genetic divergence in copper sensitivity was compared to neutral differentiation using the QST-FST approach. No evidence for homogenizing selection could be detected. This result demonstrates that species-level extrapolations from single population studies are highly unreliable. The study provides a simple example of how evolutionary principles could be incorporated into ecotoxicity testing in order to refine ecological risk assessment. Copyright © 2015 Elsevier Ltd. All rights reserved.
Recovery in environmental risk assessment at EFSA
Brock, T.C.M.
2016-01-01
EFSA performs environmental risk assessments (ERAs) for single potential stressors such as plant protection products, genetically modified organisms and feed additives and for invasive alien species that are harmful for plant health. In this risk assessment domain, the EFSA Scientific Committee
International Nuclear Information System (INIS)
Kloepffer, W.; Renner, I.; Schmidt, E.; Tappeser, B.; Gensch, C.O.; Gaugitsch, H.
2001-01-01
In the preceding project 'Life Cycle Assessment of genetically modified products as a basis for a comprehensive assessment of possible environmental effects' for the first time the risks of deliberate release of genetically modified organisms (GMOs) into the environment have been taken into account in a Life Cycle Assessment (LCA). This was performed by a risk assessment in addition to a quantitative impact assessment. As from a methodological perspective this was not satisfactory, the Federal Environment Agency commissioned the C.A.U. GmbH and the Institute of Applied Ecology Freiburg to further develop the impact assessment methodology for the risks of GMOs. Any further development of the methodology of impact assessment in LCAs has to be performed on the basis of the standard EN/ISO 14042. There are 2 options for taking into account risks of deliberate release of GMOs: 1. allocation of the potential effects resulting from the genetic modification on human beings and the environment to existing categories of the impact assessment and attempt to quantify within those existing methods of characterization; 2. development of a new category, e.g. 'effects of genetically modified crop plants'. In order to asses the possibilities under option 1 various models of characterization within the categories human toxicity, ecotoxicity and land use (appropriation of environmental space) have been analyzed. The risks of GMOs identified and dealt with in the preceding study were allocated to these categories. It seemed to be impossible to integrate the risks in existing models of characterization for human toxicity and ecotoxicity, as these are based on exposure and impact factors. The development of a factor for exposure seems possible for GMOs, however a suitable impact factor is not possible to generate. In addition it was analyzed if in other impact categories which are difficult to quantify any solutions for operationalization exist. This does not seem to be the case. As a
Brédart, Anne; Kop, Jean-Luc; Antoniou, Antonis C; Cunningham, Alex P; De Pauw, Antoine; Tischkowitz, Marc; Ehrencrona, Hans; Schmidt, Marjanka K; Dolbeault, Sylvie; Rhiem, Kerstin; Easton, Douglas F; Devilee, Peter; Stoppa-Lyonnet, Dominique; Schmutlzer, Rita
2018-03-05
The BOADICEA breast cancer (BC) risk assessment model and its associated Web Application v3 (BWA) tool are being extended to incorporate additional genetic and non-genetic BC risk factors. From an online survey through the BOADICEA website and UK, Dutch, French and Swedish national genetic societies, we explored the relationships between the usage frequencies of the BWA and six other common BC risk assessment tools and respondents' perceived importance of BC risk factors. Respondents (N = 443) varied in age, country and clinical seniority but comprised mainly genetics health professionals (82%) and BWA users (93%). Oncology professionals perceived reproductive, hormonal (exogenous) and lifestyle BC risk factors as more important in BC risk assessment compared to genetics professionals (p values personal BC history as BC risk factors. BWA use was positively related to the weight given to hormonal BC risk factors. The importance attributed to lifestyle and BMI BC risk factors was not associated with the use of BWA or any of the other tools. Next version of the BWA encompassing additional BC risk factors will facilitate more comprehensive BC risk assessment in genetics and oncology practice.
Iglesias, Adriana I; Mihaescu, Raluca; Ioannidis, John P A; Khoury, Muin J; Little, Julian; van Duijn, Cornelia M; Janssens, A Cecile J W
2014-05-01
Our main objective was to raise awareness of the areas that need improvements in the reporting of genetic risk prediction articles for future publications, based on the Genetic RIsk Prediction Studies (GRIPS) statement. We evaluated studies that developed or validated a prediction model based on multiple DNA variants, using empirical data, and were published in 2010. A data extraction form based on the 25 items of the GRIPS statement was created and piloted. Forty-two studies met our inclusion criteria. Overall, more than half of the evaluated items (34 of 62) were reported in at least 85% of included articles. Seventy-seven percentage of the articles were identified as genetic risk prediction studies through title assessment, but only 31% used the keywords recommended by GRIPS in the title or abstract. Seventy-four percentage mentioned which allele was the risk variant. Overall, only 10% of the articles reported all essential items needed to perform external validation of the risk model. Completeness of reporting in genetic risk prediction studies is adequate for general elements of study design but is suboptimal for several aspects that characterize genetic risk prediction studies such as description of the model construction. Improvements in the transparency of reporting of these aspects would facilitate the identification, replication, and application of genetic risk prediction models. Copyright © 2014 Elsevier Inc. All rights reserved.
Carstens, Keri; Anderson, Jennifer; Bachman, Pamela; De Schrijver, Adinda; Dively, Galen; Federici, Brian; Hamer, Mick; Gielkens, Marco; Jensen, Peter; Lamp, William; Rauschen, Stefan; Ridley, Geoff; Romeis, Jörg; Waggoner, Annabel
2012-08-01
Environmental risk assessments (ERA) support regulatory decisions for the commercial cultivation of genetically modified (GM) crops. The ERA for terrestrial agroecosystems is well-developed, whereas guidance for ERA of GM crops in aquatic ecosystems is not as well-defined. The purpose of this document is to demonstrate how comprehensive problem formulation can be used to develop a conceptual model and to identify potential exposure pathways, using Bacillus thuringiensis (Bt) maize as a case study. Within problem formulation, the insecticidal trait, the crop, the receiving environment, and protection goals were characterized, and a conceptual model was developed to identify routes through which aquatic organisms may be exposed to insecticidal proteins in maize tissue. Following a tiered approach for exposure assessment, worst-case exposures were estimated using standardized models, and factors mitigating exposure were described. Based on exposure estimates, shredders were identified as the functional group most likely to be exposed to insecticidal proteins. However, even using worst-case assumptions, the exposure of shredders to Bt maize was low and studies supporting the current risk assessments were deemed adequate. Determining if early tier toxicity studies are necessary to inform the risk assessment for a specific GM crop should be done on a case by case basis, and should be guided by thorough problem formulation and exposure assessment. The processes used to develop the Bt maize case study are intended to serve as a model for performing risk assessments on future traits and crops.
Lowery, Jan T; Byers, Tim; Axell, Lisen; Ku, Lisa; Jacobellis, Jillian
2008-12-01
To assess the impact of direct-to-consumer marketing for genetic testing among women of varying genetic risk for breast and ovarian cancer. Telephone surveys were conducted with 315 women in Denver, Colorado, one target audience for the Myriad BRACAnalysis ad campaign. Genetic risk was determined from personal and family history and grouped by probability of having a BRCA1/2 mutation (low or =10%). High-risk women were more knowledgeable about BRACAnalysis and more likely to recall the media ads than were low-risk women (60 vs. 39%, P audience. Concern about breast cancer was not appreciably increased. A large percentage of low-risk women (not candidates for testing) expressed interest in testing, suggesting the campaign was too broad. A campaign targeted at high-risk women, who may benefit from testing might be preferred.
Building better environmental risk assessments
Directory of Open Access Journals (Sweden)
Raymond eLayton
2015-08-01
Full Text Available Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERA for genetically modified (GM crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems – examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data, and adapting advances in risk analysis from other relevant disciplines.
Building Better Environmental Risk Assessments
Layton, Raymond; Smith, Joe; Macdonald, Phil; Letchumanan, Ramatha; Keese, Paul; Lema, Martin
2015-01-01
Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision-making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERAs) for genetically modified (GM) crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems – examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data), and adapting advances in risk analysis from other relevant disciplines. PMID:26301217
Building Better Environmental Risk Assessments.
Layton, Raymond; Smith, Joe; Macdonald, Phil; Letchumanan, Ramatha; Keese, Paul; Lema, Martin
2015-01-01
Risk assessment is a reasoned, structured approach to address uncertainty based on scientific and technical evidence. It forms the foundation for regulatory decision-making, which is bound by legislative and policy requirements, as well as the need for making timely decisions using available resources. In order to be most useful, environmental risk assessments (ERAs) for genetically modified (GM) crops should provide consistent, reliable, and transparent results across all types of GM crops, traits, and environments. The assessments must also separate essential information from scientific or agronomic data of marginal relevance or value for evaluating risk and complete the assessment in a timely fashion. Challenges in conducting ERAs differ across regulatory systems - examples are presented from Canada, Malaysia, and Argentina. One challenge faced across the globe is the conduct of risk assessments with limited resources. This challenge can be overcome by clarifying risk concepts, placing greater emphasis on data critical to assess environmental risk (for example, phenotypic and plant performance data rather than molecular data), and adapting advances in risk analysis from other relevant disciplines.
Risk assessment research and technology assessment
International Nuclear Information System (INIS)
Albach, H.; Schade, D.; Sinn, H.
1991-01-01
The concepts and approaches for technology assessment, the targets and scientific principles, as well as recognizable deficits and recommendations concerning purposeful strategies for the promotion of this research field require a dialog between those concerned. Conception, deficits, and the necessary measures for risk assessment research and technology assessment were discussed as well as ethical aspects. The problematic nature of using organisms altered through genetic engineering in the open land, traffic and transport, site restoration, nuclear energy, and isotope applications were subjects particularly dealt with. (DG) [de
Kuiper, H A; König, A; Kleter, G A; Hammes, W P; Knudsen, I
2004-07-01
The most important results from the EU-sponsored ENTRANSFOOD Thematic Network project are reviewed, including the design of a detailed step-wise procedure for the risk assessment of foods derived from genetically modified crops based on the latest scientific developments, evaluation of topical risk assessment issues, and the formulation of proposals for improved risk management and public involvement in the risk analysis process. Copyright 2004 Elsevier Ltd.
Directory of Open Access Journals (Sweden)
Alan Raybould
2018-04-01
Full Text Available We describe two contrasting methods of comparative environmental risk assessment for genetically modified (GM crops. Both are science-based, in the sense that they use science to help make decisions, but they differ in the relationship between science and policy. Policy-led comparative risk assessment begins by defining what would be regarded as unacceptable changes when the use a particular GM crop replaces an accepted use of another crop. Hypotheses that these changes will not occur are tested using existing or new data, and corroboration or falsification of the hypotheses is used to inform decision-making. Science-led comparative risk assessment, on the other hand, tends to test null hypotheses of no difference between a GM crop and a comparator. The variables that are compared may have little or no relevance to any previously stated policy objective and hence decision-making tends to be ad hoc in response to possibly spurious statistical significance. We argue that policy-led comparative risk assessment is the far more effective method. With this in mind, we caution that phenotypic profiling of GM crops, particularly with omics methods, is potentially detrimental to risk assessment.
Development of a construct-based risk assessment framework for genetic engineered crops.
Beker, M P; Boari, P; Burachik, M; Cuadrado, V; Junco, M; Lede, S; Lema, M A; Lewi, D; Maggi, A; Meoniz, I; Noé, G; Roca, C; Robredo, C; Rubinstein, C; Vicien, C; Whelan, A
2016-10-01
Experience gained in the risk assessment (RA) of genetically engineered (GE) crops since their first experimental introductions in the early nineties, has increased the level of familiarity with these breeding methodologies and has motivated several agencies and expert groups worldwide to revisit the scientific criteria underlying the RA process. Along these lines, the need to engage in a scientific discussion for the case of GE crops transformed with similar constructs was recently identified in Argentina. In response to this need, the Argentine branch of the International Life Sciences Institute (ILSI Argentina) convened a tripartite working group to discuss a science-based evaluation approach for transformation events developed with genetic constructs which are identical or similar to those used in previously evaluated or approved GE crops. This discussion considered new transformation events within the same or different species and covered both environmental and food safety aspects. A construct similarity concept was defined, considering the biological function of the introduced genes. Factors like environmental and dietary exposure, familiarity with both the crop and the trait as well as the crop biology, were identified as key to inform a construct-based RA process.
Grant, Richard W; Meigs, James B; Florez, Jose C; Park, Elyse R; Green, Robert C; Waxler, Jessica L; Delahanty, Linda M; O'Brien, Kelsey E
2011-10-01
justified because genotype represents a random allocation of parental alleles ('Mendelian randomization'). Finally, because it would be unethical to discourage participants to participate in diabetes prevention behaviors, we designed our two diabetes genetic risk counseling interventions (for 'higher' and 'lower' result recipients) so that both groups would be motivated despite receiving opposing results. For this initial assessment of the clinical implementation of genetic risk testing we assessed intermediate outcomes of attendance at a 12-week diabetes prevention course and changes in self-reported motivation. If effective, longer term studies with larger sample sizes will be needed to assess whether knowledge of diabetes genetic risk can help patients prevent diabetes. We designed a randomized clinical trial designed to explore the motivational impact of disclosing both higher than average and lower than average genetic risk for type 2 diabetes. This design allowed exploration of both increased risk and false reassurance, and has implications for future studies in translational genomics.
Directory of Open Access Journals (Sweden)
Hong-Lian Ruan
Full Text Available To date, the only established model for assessing risk for nasopharyngeal carcinoma (NPC relies on the sero-status of the Epstein-Barr virus (EBV. By contrast, the risk assessment models proposed here include environmental risk factors, family history of NPC, and information on genetic variants. The models were developed using epidemiological and genetic data from a large case-control study, which included 1,387 subjects with NPC and 1,459 controls of Cantonese origin. The predictive accuracy of the models were then assessed by calculating the area under the receiver-operating characteristic curves (AUC. To compare the discriminatory improvement of models with and without genetic information, we estimated the net reclassification improvement (NRI and integrated discrimination index (IDI. Well-established environmental risk factors for NPC include consumption of salted fish and preserved vegetables and cigarette smoking (in pack years. The environmental model alone shows modest discriminatory ability (AUC = 0.68; 95% CI: 0.66, 0.70, which is only slightly increased by the addition of data on family history of NPC (AUC = 0.70; 95% CI: 0.68, 0.72. With the addition of data on genetic variants, however, our model's discriminatory ability rises to 0.74 (95% CI: 0.72, 0.76. The improvements in NRI and IDI also suggest the potential usefulness of considering genetic variants when screening for NPC in endemic areas. If these findings are confirmed in larger cohort and population-based case-control studies, use of the new models to analyse data from NPC-endemic areas could well lead to earlier detection of NPC.
Risk perception after genetic counseling in patients with increased risk of cancer
Directory of Open Access Journals (Sweden)
Rantala Johanna
2009-08-01
Full Text Available Abstract Background Counselees are more aware of genetics and seek information, reassurance, screening and genetic testing. Risk counseling is a key component of genetic counseling process helping patients to achieve a realistic view for their own personal risk and therefore adapt to the medical, psychological and familial implications of disease and to encourage the patient to make informed choices 12. The aim of this study was to conceptualize risk perception and anxiety about cancer in individuals attending to genetic counseling. Methods The questionnaire study measured risk perception and anxiety about cancer at three time points: before and one week after initial genetic counseling and one year after completed genetic investigations. Eligibility criteria were designed to include only index patients without a previous genetic consultation in the family. A total of 215 individuals were included. Data was collected during three years period. Results Before genetic counseling all of the unaffected participants subjectively estimated their risk as higher than their objective risk. Participants with a similar risk as the population overestimated their risk most. All risk groups estimated the risk for children's/siblings to be lower than their own. The benefits of preventive surveillance program were well understood among unaffected participants. The difference in subjective risk perception before and directly after genetic counseling was statistically significantly lower in all risk groups. Difference in risk perception for children as well as for population was also statistically significant. Experienced anxiety about developing cancer in the unaffected subjects was lower after genetic counseling compared to baseline in all groups. Anxiety about cancer had clear correlation to perceived risk of cancer before and one year after genetic investigations. The affected participants overestimated their children's risk as well as risk for anyone in
Likelihood ratio-based integrated personal risk assessment of type 2 diabetes.
Sato, Noriko; Htun, Nay Chi; Daimon, Makoto; Tamiya, Gen; Kato, Takeo; Kubota, Isao; Ueno, Yoshiyuki; Yamashita, Hidetoshi; Fukao, Akira; Kayama, Takamasa; Muramatsu, Masaaki
2014-01-01
To facilitate personalized health care for multifactorial diseases, risks of genetic and clinical/environmental factors should be assessed together for each individual in an integrated fashion. This approach is possible with the likelihood ratio (LR)-based risk assessment system, as this system can incorporate manifold tests. We examined the usefulness of this system for assessing type 2 diabetes (T2D). Our system employed 29 genetic susceptibility variants, body mass index (BMI), and hypertension as risk factors whose LRs can be estimated from openly available T2D association data for the Japanese population. The pretest probability was set at a sex- and age-appropriate population average of diabetes prevalence. The classification performance of our LR-based risk assessment was compared to that of a non-invasive screening test for diabetes called TOPICS (with score based on age, sex, family history, smoking, BMI, and hypertension) using receiver operating characteristic analysis with a community cohort (n = 1263). The area under the receiver operating characteristic curve (AUC) for the LR-based assessment and TOPICS was 0.707 (95% CI 0.665-0.750) and 0.719 (0.675-0.762), respectively. These AUCs were much higher than that of a genetic risk score constructed using the same genetic susceptibility variants, 0.624 (0.574-0.674). The use of ethnically matched LRs is necessary for proper personal risk assessment. In conclusion, although LR-based integrated risk assessment for T2D still requires additional tests that evaluate other factors, such as risks involved in missing heritability, our results indicate the potential usability of LR-based assessment system and stress the importance of stratified epidemiological investigations in personalized medicine.
Pott, Antonia; Otto, Mathias; Schulz, Ralf
2018-09-01
The aquatic environment is strongly connected to the surrounding agricultural landscapes, which regularly serve as sources of stressors such as agrochemicals. Genetically modified crops, which are cultivated on a large scale in many countries, may also act as stressors. Despite the commercial use of genetically modified organisms (GMOs) for over 20years, their impact on the aquatic environment came into focus only 10years ago. We present the status quo of the available scientific data in order to provide an input for informed aquatic risk assessment of GMOs. We could identify only 39 publications, including 84 studies, dealing with GMOs in the aquatic environment, and our analysis shows substantial knowledge gaps. The available information is restricted to a small number of crop plants, traits, events, and test organisms. The analysis of effect studies reveals that only a narrow range of organisms has been tested and that studies on combinatorial actions of stressors are virtually absent. The analysis of fate studies shows that many aspects, such as the fate of leached toxins, degradation of plant material, and distribution of crop residues in the aquatic habitat, are insufficiently investigated. Together with these research needs, we identify standardization of test methods as an issue of high priority, both for research and risk assessment needed for GMO regulation. Copyright © 2018 Elsevier B.V. All rights reserved.
Applying Evolutionary Genetics to Developmental Toxicology and Risk Assessment
Leung, Maxwell C. K.; Procter, Andrew C.; Goldstone, Jared V.; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J.; Siddall, Mark E.; Timme-Laragy, Alicia R.
2018-01-01
Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease. PMID:28267574
Genetic variants in hormone-related genes and risk of breast cancer.
Directory of Open Access Journals (Sweden)
Tess Clendenen
Full Text Available Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.
The potential of large studies for building genetic risk prediction models
NCI scientists have developed a new paradigm to assess hereditary risk prediction in common diseases, such as prostate cancer. This genetic risk prediction concept is based on polygenic analysis—the study of a group of common DNA sequences, known as singl
Cardiovascular genetic assessment and treatment in middle age to ...
African Journals Online (AJOL)
Assessment and treatment of cardiovascular disease (CVD) risk factors as a preventable cause of cognitive decline, morbidity and mortality is an important clinical goal. The apolipoprotein E (Apo E) gene provides a genetic link between CVD and the development of Alzheimer's disease (AD). The E4 allele increases the risk ...
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
Cost sharing and hereditary cancer risk: predictors of willingness-to-pay for genetic testing.
Matro, Jennifer M; Ruth, Karen J; Wong, Yu-Ning; McCully, Katen C; Rybak, Christina M; Meropol, Neal J; Hall, Michael J
2014-12-01
Increasing use of predictive genetic testing to gauge hereditary cancer risk has been paralleled by rising cost-sharing practices. Little is known about how demographic and psychosocial factors may influence individuals' willingness-to-pay for genetic testing. The Gastrointestinal Tumor Risk Assessment Program Registry includes individuals presenting for genetic risk assessment based on personal/family cancer history. Participants complete a baseline survey assessing cancer history and psychosocial items. Willingness-to-pay items include intention for: genetic testing only if paid by insurance; testing with self-pay; and amount willing-to-pay ($25-$2,000). Multivariable models examined predictors of willingness-to-pay out-of-pocket (versus only if paid by insurance) and willingness-to-pay a smaller versus larger sum (≤$200 vs. ≥$500). All statistical tests are two-sided (α = 0.05). Of 385 evaluable participants, a minority (42%) had a personal cancer history, while 56% had ≥1 first-degree relative with colorectal cancer. Overall, 21.3% were willing to have testing only if paid by insurance, and 78.7% were willing-to-pay. Predictors of willingness-to-pay were: 1) concern for positive result; 2) confidence to control cancer risk; 3) fewer perceived barriers to colorectal cancer screening; 4) benefit of testing to guide screening (all p testing (all p testing, and anticipate benefits to reducing cancer risk. Identifying factors associated with willingness-to-pay for genetic services is increasingly important as testing is integrated into routine cancer care.
Genetic risks of ionizing radiation
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1990-01-01
Quantitative genetic risk estimation is made using two methods: the direct method, and the doubling dose (DD) method. The doubling dose currently used is 1 Gy for low LET, low dose, low dose rate irradiation, and is based on mouse data. Tables present the 1988 UNSCEAR estimates of genetic risk using both methods. (L.L.) (Tab.)
Wilson, R Douglas
2017-10-11
To inform reproductive and other health care providers about genetic and fetal risk information to consider during a woman/couples' pre-conception evaluation, including considerations for genetic risk assessment, genetic screening, or testing to allow for improved counselling and informed choice. This genetic information can be used for patient education, planning, and possible pre-conception and/or prenatal testing. This information may allow improved risk assessment for pre-conception counselling for individual patients and their families. PubMed or Medline and the Cochrane Database were searched in May 2017 using appropriate key words ("pre-conception," "genetic disease," "maternal," "family history," "genetic," "health risk," "genetic health surveillance," "prenatal screening," "prenatal diagnosis," "birth defects," and "teratogen"). Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, and national and international medical specialty societies. The benefits for the patient and her family include an increased understanding of relevant genetic risk pre-conception and in early pregnancy, and better pregnancy outcomes as a result of use of the information. The harm includes potential increased anxiety or psychological stress associated with the possibility of identifying genetic risks. The evidence obtained was peer-reviewed by the Genetics Committee of The Society of Obstetricians and Gynaecologists of Canada. Consideration for Care Statements For this review article, the Consideration for Care Statements use the GRADE strength and quality as it is comparable for the clinician and the patient/public user. [GRADE from the Canadian Task Force on Preventive Health Care (www.canadiantaskforce.ca). For clinicians, Strong = The recommendation would apply to most individuals. Formal discussion aids are not likely to be
Risk assessment model for development of advanced age-related macular degeneration.
Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E
2011-12-01
To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.
DEFF Research Database (Denmark)
Borch, K.; Rasmussen, B.; Schleisner, L.
2000-01-01
important and uncertain fac-tors for the future direction of GM crops: 1) publicparticipation in regulation, 2) utility value for the consumers, 3) being first to market GM-ryegrass, and 4) an efficient professional network. Based on the identified drivers several scenar-ios were constructed, of which two......, a methodological approach is suggested to analyse the uncertainties that the biotech industry and the authorities face when implementing genetically modified (GM) crops. These uncertainties embracescientific rationality regarding technological development and risk assessments, as well as ethic political and social...
Goedhart, Paul W; van der Voet, Hilko; Baldacchino, Ferdinando; Arpaia, Salvatore
2014-04-01
Genetic modification of plants may result in unintended effects causing potentially adverse effects on the environment. A comparative safety assessment is therefore required by authorities, such as the European Food Safety Authority, in which the genetically modified plant is compared with its conventional counterpart. Part of the environmental risk assessment is a comparative field experiment in which the effect on non-target organisms is compared. Statistical analysis of such trials come in two flavors: difference testing and equivalence testing. It is important to know the statistical properties of these, for example, the power to detect environmental change of a given magnitude, before the start of an experiment. Such prospective power analysis can best be studied by means of a statistical simulation model. This paper describes a general framework for simulating data typically encountered in environmental risk assessment of genetically modified plants. The simulation model, available as Supplementary Material, can be used to generate count data having different statistical distributions possibly with excess-zeros. In addition the model employs completely randomized or randomized block experiments, can be used to simulate single or multiple trials across environments, enables genotype by environment interaction by adding random variety effects, and finally includes repeated measures in time following a constant, linear or quadratic pattern in time possibly with some form of autocorrelation. The model also allows to add a set of reference varieties to the GM plants and its comparator to assess the natural variation which can then be used to set limits of concern for equivalence testing. The different count distributions are described in some detail and some examples of how to use the simulation model to study various aspects, including a prospective power analysis, are provided.
Personalized Genetic Risk Counseling to Motivate Diabetes Prevention
Grant, Richard W.; O’Brien, Kelsey E.; Waxler, Jessica L.; Vassy, Jason L.; Delahanty, Linda M.; Bissett, Laurie G.; Green, Robert C.; Stember, Katherine G.; Guiducci, Candace; Park, Elyse R.; Florez, Jose C.; Meigs, James B.
2012-01-01
OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top an...
International Nuclear Information System (INIS)
Strel'nikova, N.K.
1989-01-01
On the basis of the available data an evaluation of genetic radiation risk during roentgenologic examination of women of the reproductive age is presented. It is demonstrated that the degree of genetic risk depends on woman's age at the moment of the roentgenologic examination and the amount of the gonadal dose. Identification of the high-risk exposed populations has been substantiated
Genetic variants and multiple myeloma risk
DEFF Research Database (Denmark)
Martino, Alessandro; Campa, Daniele; Jurczyszyn, Artur
2014-01-01
BACKGROUND: Genetic background plays a role in multiple myeloma susceptibility. Several single-nucleotide polymorphisms (SNP) associated with genetic susceptibility to multiple myeloma were identified in the last years, but only a few of them were validated in independent studies. METHODS...... with multiple myeloma risk (P value range, 0.055-0.981), possibly with the exception of the SNP rs2227667 (SERPINE1) in women. CONCLUSIONS: We can exclude that the selected polymorphisms are major multiple myeloma risk factors. IMPACT: Independent validation studies are crucial to identify true genetic risk...
Vassy, Jason L; O'Brien, Kelsey E; Waxler, Jessica L; Park, Elyse R; Delahanty, Linda M; Florez, Jose C; Meigs, James B; Grant, Richard W
2012-01-01
Type 2 diabetes genetic risk testing might motivate at-risk patients to adopt diabetes prevention behaviors. However, the influence of literacy and numeracy on patient response to diabetes genetic risk is unknown. The authors investigated the association of health literacy, genetic literacy, and health numeracy with patient responses to diabetes genetic risk. and Measurements Overweight patients at high phenotypic risk for type 2 diabetes were recruited for a clinical trial of diabetes genetic risk testing. At baseline, participants predicted how their motivation for lifestyle modification to prevent diabetes might change in response to hypothetical scenarios of receiving "high" and "low" genetic risk results. Responses were analyzed according to participants' health literacy, genetic literacy, and health numeracy. Two-thirds (67%) of participants (n = 175) reported very high motivation to prevent diabetes. Despite high health literacy (92% at high school level), many participants had limited health numeracy (30%) and genetic literacy (38%). Almost all (98%) reported that high-risk genetic results would increase their motivation for lifestyle modification. In contrast, response to low-risk genetic results varied. Higher levels of health literacy (P = 0.04), genetic literacy (P = 0.02), and health numeracy (P = 0.02) were associated with an anticipated decrease in motivation for lifestyle modification in response to low-risk results. While patients reported that high-risk genetic results would motivate them to adopt healthy lifestyle changes, response to low-risk results varied by patient numeracy and literacy. However, anticipated responses may not correlate with true behavior change. If future research justifies the clinical use of genetic testing to motivate behavior change, it may be important to assess how patient characteristics modify that motivational effect.
Cicero, G; De Luca, R; Dorangricchia, P; Lo Coco, G; Guarnaccia, C; Fanale, D; Calò, V; Russo, A
2017-10-01
Oncological Genetic Counselling (CGO) allows the identification of a genetic component that increases the risk of developing a cancer. Individuals' psychological reactions are influenced by both the content of the received information and the subjective perception of their own risk of becoming ill or being a carrier of a genetic mutation. This study included 120 participants who underwent genetic counselling for breast and/or ovarian cancer. The aim of the study was to examine the relation between their cancer risk perception and the genetic risk during CGO before receiving genetic test results, considering the influence of some psychological variables, in particular distress, anxiety and depression. Participants completed the following tools during a psychological interview: a socio-demographic form, Cancer Risk Perception (CRP) and Genetic Risk Perception (GRP), Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT). The data seem to confirm our hypothesis. Positive and significant correlations were found between the observed variables. Moreover, genetic risk perception determined an increase in depressive symptomatology and cancer risk perception led to an increase in anxious symptomatology, specifically in participants during cancer treatment. The present results suggest the importance of assessing genetic and cancer risk perception in individuals who undergo CGO, to identify those who are at risk of a decrease in psychological well-being and of developing greater psychological distress.
Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L; Hayden, Michael R
2009-01-01
Objective To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington?s disease who had undergone genetic testing or remained untested. Design Cross sectional, self reported survey. Setting Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. Participants 233 genetically tested and untested asymptomatic people at risk for Huntington?s disease (response rate 80%): 167 underwent testing (83 had the Huntingt...
Quantifying introgression risk with realistic population genetics.
Ghosh, Atiyo; Meirmans, Patrick G; Haccou, Patsy
2012-12-07
Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified crop regulation. Most theoretical introgression studies aimed at such quantification disregard one or more of the most important factors concerning introgression: realistic genetical mechanisms, repeated invasions and stochasticity. In addition, the use of linkage as a risk mitigation strategy has not been studied properly yet with genetic introgression models. Current genetic introgression studies fail to take repeated invasions and demographic stochasticity into account properly, and use incorrect measures of introgression risk that can be manipulated by arbitrary choices. In this study, we present proper methods for risk quantification that overcome these difficulties. We generalize a probabilistic risk measure, the so-called hazard rate of introgression, for application to introgression models with complex genetics and small natural population sizes. We illustrate the method by studying the effects of linkage and recombination on transgene introgression risk at different population sizes.
DEFF Research Database (Denmark)
Obel, Niels; Christensen, Kaare; Petersen, Inge
2010-01-01
Genetic differences have been proposed to play a strong role in risk of death from infectious diseases. The study base of 44,005 included all same-sex twin pairs born in 1870-2001, with both twins alive on January 1, 1943, or those born thereafter. Cause of death was obtained from the Danish Cause...... from infectious diseases could be demonstrated, the absolute effect of the genetic component on mortality was small....... genetic influence on the risk of death...
Brown, Sherry-Ann; Jouni, Hayan; Marroush, Tariq S; Kullo, Iftikhar J
2017-04-01
Incorporating genetic risk information in electronic health records (EHRs) will facilitate implementation of genomic medicine in clinical practice. However, little is known about patients' attitudes toward incorporation of genetic risk information as a component of personal health information in EHRs. This study investigated whether disclosure of a genetic risk score (GRS) for coronary heart disease influences attitudes toward incorporation of personal health information including genetic risk in EHRs. Participants aged 45-65 years with intermediate 10-year coronary heart disease risk were randomized to receive a conventional risk score (CRS) alone or with a GRS from a genetic counselor, followed by shared decision making with a physician using the same standard presentation and information templates for all study participants. The CRS and GRS were then incorporated into the EHR and made accessible to both patients and physicians. Baseline and post-disclosure surveys were completed to assess whether attitudes differed by GRS disclosure. Data were collected from 2013 to 2015 and analyzed in 2015-2016. GRS and CRS participants reported similar positive attitudes toward incorporation of genetic risk information in the EHR. Compared with CRS participants, participants with high GRS were more concerned about the confidentiality of genetic risk information (OR=3.67, 95% CI=1.29, 12.32, p=0.01). Post-disclosure, frequency of patient portal access was associated with positive attitudes. Participants in this study of coronary heart disease risk disclosure overall had positive attitudes toward incorporation of genetic risk information in EHRs, although those who received genetic risk information had concerns about confidentiality. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
The impact of advances in human molecular biology on radiation genetic risk estimation in man
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1996-01-01
This paper provides an overview of the conceptual framework, the data base, methods and assumptions used thus far to assess the genetic risks of exposure of human populations to ionising radiation. These are then re-examined in the contemporary context of the rapidly expanding knowledge of the molecular biology of human mendelian diseases. This re-examination reveals that (i) many of the assumptions used thus far in radiation genetic risk estimation may not be fully valid and (ii) the current genetic risk estimates are probably conservative, but provide an adequate margin of safety for radiological protection. The view is expressed that further advances in the field of genetic risk estimation will be largely driven by advances in the molecular biology of human genetic diseases. (author). 37 refs., 5 tabs
Kengne-Ouafo, Jonas A; Millard, James D; Nji, Theobald M; Tantoh, William F; Nyoh, Doris N; Tendongfor, Nicholas; Enyong, Peter A; Newport, Melanie J; Davey, Gail; Wanji, Samuel
2016-05-01
There is limited assessment of whether research participants in low-income settings are afforded a full understanding of the meaning of medical research. There may also be particular issues with the understanding of genetic research. We used a rapid ethical assessment methodology to explore perceptions surrounding the meaning of research, genetics and genetic research in north west Cameroon. Eleven focus group discussions (including 107 adults) and 72 in-depth interviews were conducted with various stakeholders in two health districts in north west Cameroon between February and April 2012. Most participants appreciated the role of research in generating knowledge and identified a difference between research and healthcare but gave varied explanations as to this difference. Most participants' understanding of genetics was limited to concepts of hereditary, with potential benefits limited to the level of the individual or family. Explanations based on supernatural beliefs were identified as a special issue but participants tended not to identify any other special risks with genetic research. We demonstrated a variable level of understanding of research, genetics and genetic research, with implications for those carrying out genetic research in this and other low resource settings. Our study highlights the utility of rapid ethical assessment prior to complex or sensitive research. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.
Devos, Yann; Aguilera, Jaime; Diveki, Zoltán; Gomes, Ana; Liu, Yi; Paoletti, Claudia; du Jardin, Patrick; Herman, Lieve; Perry, Joe N; Waigmann, Elisabeth
2014-02-01
Genetically modified organisms (GMOs) and derived food and feed products are subject to a risk analysis and regulatory approval before they can enter the market in the European Union (EU). In this risk analysis process, the role of the European Food Safety Authority (EFSA), which was created in 2002 in response to multiple food crises, is to independently assess and provide scientific advice to risk managers on any possible risks that the use of GMOs may pose to human and animal health and the environment. EFSA's scientific advice is elaborated by its GMO Panel with the scientific support of several working groups and EFSA's GMO Unit. This review presents EFSA's scientific activities and highlights its achievements on the risk assessment of GMOs for the first 10 years of its existence. Since 2002, EFSA has issued 69 scientific opinions on genetically modified (GM) plant market registration applications, of which 62 for import and processing for food and feed uses, six for cultivation and one for the use of pollen (as or in food), and 19 scientific opinions on applications for marketing products made with GM microorganisms. Several guidelines for the risk assessment of GM plants, GM microorganisms and GM animals, as well as on specific issues such as post-market environmental monitoring (PMEM) were elaborated. EFSA also provided scientific advice upon request of the European Commission on safeguard clause and emergency measures invoked by EU Member States, annual PMEM reports, the potential risks of new biotechnology-based plant breeding techniques, evaluations of previously assessed GMOs in the light of new scientific publications, and the use of antibiotic resistance marker genes in GM plants. Future challenges relevant to the risk assessment of GMOs are discussed. EFSA's risk assessments of GMO applications ensure that data are analysed and presented in a way that facilitates scientifically sound decisions that protect human and animal health and the environment.
Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem
2018-03-14
Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle
Characterizing the genetic influences on risk aversion.
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.
Methods to estimate the genetic risk
International Nuclear Information System (INIS)
Ehling, U.H.
1989-01-01
The estimation of the radiation-induced genetic risk to human populations is based on the extrapolation of results from animal experiments. Radiation-induced mutations are stochastic events. The probability of the event depends on the dose; the degree of the damage dose not. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of expected frequencies of genetic changes induced per unit dose. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The advantage of the indirect method is that not only can Mendelian mutations be quantified, but also other types of genetic disorders. The disadvantages of the method are the uncertainties in determining the current incidence of genetic disorders in human and, in addition, the estimasion of the genetic component of congenital anomalies, anomalies expressed later and constitutional and degenerative diseases. Using the direct method we estimated that 20-50 dominant radiation-induced mutations would be expected in 19 000 offspring born to parents exposed in Hiroshima and Nagasaki, but only a small proportion of these mutants would have been detected with the techniques used for the population study. These methods were used to predict the genetic damage from the fallout of the reactor accident at Chernobyl in the vicinity of Southern Germany. The lack of knowledge for the interaction of chemicals with ionizing radiation and the discrepancy between the high safety standards for radiation protection and the low level of knowledge for the toxicological evaluation of chemical mutagens will be emphasized. (author)
Biosafety risk assessment approaches for insect-resistant genetically modified crops
Directory of Open Access Journals (Sweden)
Inaam Ullah
2017-02-01
Full Text Available Background: Environmental risk assessment (ERA is imperative for commercial release of insect resistant, genetically modified crops (IR-GMCs.An insect specific, spider venom peptideω-HXTX-Hv1a (Hvt was successfully expressed in cotton plants. The cotton plants producing Hvt protein have demonstrated resistance against economically important insect pest species. The study was performed to assess the effects of Hvt producing cotton plants on Honey bees (Apis mellifera. Methods: Three approaches were used to evaluate the effects of Hvt protein on adults of honeybees; whole plant assays in flight cages, in vitro assays with pollen of Hvt-cotton, and assays with elevated levels of purified Hvt protein. Pollens of Bt cotton or purified Bt proteins were used as control. Results: The field experiments did not yield any meaningful data due to high rate of mortality in all treatments including the control. However, the laboratory experiments provided conclusive results in which Hvt, purified or in pollens, did not affect the survival or longevity of the bees compared to the control. During the course of study we were able to compare the quality, effectiveness and economics of different experiments. Conclusions: We conclude that Hvt either purified or produced in cotton plants do not affect the survival or longevity of honey bees. We are also of the view that starting at laboratory level assays not only gives meaningful data but also saves a lot of time and money that can be spent on other important questions regarding safety of a particular transgenic crop. Hence, a purpose-based, tiered approach could be the best choice for pre-release ERA of IR-GMCs.
Omega-3 fatty acids and the genetic risk of early onset acute coronary syndrome.
Leung Yinko, S S L; Thanassoulis, G; Stark, K D; Avgil Tsadok, M; Engert, J C; Pilote, L
2014-11-01
Recent gene-environment interaction studies suggest that diet may influence an individual's genetic predisposition to cardiovascular risk. We evaluated whether omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with early onset ACS. Our population consisted of 705 patients of white European descent enrolled in GENESIS-PRAXY, a multicenter cohort study of patients aged 18-55 years and hospitalized with ACS. We used a case-only design to investigate interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) robustly associated with ACS. We used logistic regression to assess the interaction between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs. All models were adjusted for age and sex. An interaction for increased ACS risk was found between carriers of the chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p = 0.02), but this was not significant after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p = 0.03). We did not observe any interaction between the genetic risk score or any of the other SNPs and the omega-3 index. Our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation in the development of early onset ACS and requires independent replication. Copyright © 2014 Elsevier B.V. All rights reserved.
Risk assesment in the context of EC directives on genetically modified organisms
Energy Technology Data Exchange (ETDEWEB)
Meer, P.J. van der [Ministry for the Environment (Netherlands)
1992-07-01
The introduction of these new molecular technologies initiated an international discussion on the safety in biotechnology. In 1974 one of the pioneers of this new technology, Paul Berg, expressed his view on the potential risks of recombinant DNA applications in the famous 'Berg letter', leading to a self-imposed moratorium on certain experiments. Following the Berg letter and the Asilomar convention, much international attention has been given to the question of safety in biotechnology. This attention resulted in hundreds of documents, research programmes, guidelines and regulations. This resulted, among others, in two EC Directives on genetically modified organisms: the EC Directive 90/219/EEC on the contained use of genetically modified micro-organisms, and Directive 90/220/EEC on the release of genetically modified organisms. These directives lay down a system for harmonization of risk assessment and risk management with regard to the safety for human health and the environment.
Risk assesment in the context of EC directives on genetically modified organisms
International Nuclear Information System (INIS)
Meer, P.J. van der
1992-01-01
The introduction of these new molecular technologies initiated an international discussion on the safety in biotechnology. In 1974 one of the pioneers of this new technology, Paul Berg, expressed his view on the potential risks of recombinant DNA applications in the famous 'Berg letter', leading to a self-imposed moratorium on certain experiments. Following the Berg letter and the Asilomar convention, much international attention has been given to the question of safety in biotechnology. This attention resulted in hundreds of documents, research programmes, guidelines and regulations. This resulted, among others, in two EC Directives on genetically modified organisms: the EC Directive 90/219/EEC on the contained use of genetically modified micro-organisms, and Directive 90/220/EEC on the release of genetically modified organisms. These directives lay down a system for harmonization of risk assessment and risk management with regard to the safety for human health and the environment
2009-01-01
In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers. PMID:21637504
Directory of Open Access Journals (Sweden)
Thadeu Estevam Moreira Maramaldo Costa
2011-01-01
Full Text Available Desde o começo de sua comercialização, em 1996, a área global de plantações transgênicas aumentou mais de cinquenta vezes. Nas duas últimas décadas, organizações governamentais e intergovernamentais têm planejado estratégias e protocolos para o estudo da segurança de alimentos derivados de cultivos geneticamente modificados. Os testes de segurança são realizados caso a caso e conduzidos de acordo com as características específicas das culturas modificadas e as mudanças introduzidas através da modificação genética, levando em conta o conceito de equivalência substancial. No presente trabalho, estão relatadas algumas abordagens de avaliação de risco de alimentos geneticamente modificados, assim como alguns problemas relacionados à construção genética ou mesmo à expressão do gene inseridoSince the commercial approve in 1996, the global area of transgenic crops has raised more than 50 times. In the last two decades, governments have been planning strategies and protocols for safety assessment of food and feed genetically modified (GM. Evaluation of food safety should be taken on a case-by-case analysis depending on the specific traits of the modified crops and the changes introduced by the genetic modification, using for this the concept of substantial equivalence. This work presents approaches for the risk assessment of GM food, as well as some problems related with the genetic construction or even with the expression of the inserted gene
Christensen, Kurt D.; Roberts, J. Scott; Uhlmann, Wendy R.; Green, Robert C.
2011-01-01
Purpose Perceptions about the pros and cons of genetic susceptibility testing are among the best predictors of test utilization. How actual testing changes such perceptions has yet to be examined. Methods In a clinical trial, first-degree relatives of patients with Alzheimer disease received genetic risk assessments for Alzheimer disease including APOE disclosure. Participants rated 11 possible benefits associated with genetic testing (pros) and 10 risks or limitations (cons) before genetic risk disclosure and again 12 months afterward. Results Pros were rated higher than cons at baseline (3.53 vs. 1.83, P cons did not change (1.88 vs. 1.83, P = 0.199) except for a three-item discrimination subscale which increased (2.07 vs. 1.92, P = 0.012). Among specific pros and cons, three items related to prevention and treatment changed the most. Conclusion The process of APOE genetic risk assessment for Alzheimer disease sensitizes some to its limitations and the risks of discrimination; however, 1-year after disclosure, test recipients still consider the pros to strongly outweigh the cons. PMID:21270636
Mrena, S; Savola, K; Kulmala, P; Reijonen, H; Ilonen, J; Akerblom, H K; Knip, M
2003-06-01
We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR). Genetic susceptibility to type 1 diabetes was defined by human leukocyte antigen identity and DR and DQ genotypes. There was a higher proportion of siblings with late prediabetes initially among those with strong genetic disease susceptibility than among those with decreased genetic predisposition (16.7% vs. 0.5%; P siblings with no signs of prediabetes among those with genotypes conferring decreased risk (91.2% vs. 70.4% among those with high-risk DQB1 genotypes; P siblings than when combined with genetic susceptibility. Genetic susceptibility played a role in whether the initial prediabetic stage progressed (progression in 29.6% of the high-risk siblings compared with 6.6% of the siblings with DQB1 genotypes conferring decreased risk; P siblings of affected children.
Arranging marriage; negotiating risk: genetics and society in Qatar.
Kilshaw, Susie; Al Raisi, Tasneem; Alshaban, Fouad
2015-01-01
This paper considers how the globalized discourse of genetic risk in cousin marriage is shaped, informed and taken up in local moral worlds within the context of Qatar. This paper investigates the way Qataris are negotiating the discourse on genetics and risk. It is based on data from ongoing ethnographic research in Qatar and contributes to anthropological knowledge about this understudied country. Participants were ambivalent about genetic risks and often pointed to other theories of causation in relation to illness and disability. The discourse on genetic risk associated with marrying in the family was familiar, but for some participants the benefits of close marriage outweighed potential risks. Furthermore, the introduction of mandatory pre-marital screening gave participants confidence that risks were monitored and minimized.
Lawrence, Ryan E; Friesen, Phoebe; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa
Genetic tests for schizophrenia may introduce risks and benefits. Among young adults at clinical high-risk for psychosis, little is known about their concerns and how they assess potential risks. We conducted semi-structured interviews with 15 young adults at clinical high-risk for psychosis to ask about their concerns. Participants expressed concerns about test reliability, data interpretation, stigma, psychological harm, family planning, and privacy. Participants' responses showed some departure from the ethics literature insofar as participants were primarily interested in reporting their results to people to whom they felt emotionally close, and expressed little consideration of biological closeness. Additionally, if tests showed an increased genetic risk for schizophrenia, four clinical high-risk persons felt obligated to tell an employer and another three would "maybe" tell an employer, even in the absence of clinical symptoms. These findings suggest opportunities for clinicians and genetic counselors to intervene with education and support.
Watson, M; Lloyd, S; Davidson, J; Meyer, L; Eeles, R; Ebbs, S; Murday, V
1999-02-01
The present study investigated: (1) perception of genetic risk and, (2) the psychological effects of genetic counselling in women with a family history of breast cancer. Using a prospective design, with assessment pre- and post-genetic counselling at clinics and by postal follow-up at 1, 6 and 12 months, attenders at four South London genetic clinics were assessed. Participants included 282 women with a family history of breast cancer. Outcome was measured in terms of mental health, cancer-specific distress and risk perception. High levels of cancer-specific distress were found pre-genetic counselling, with 28% of participants reporting that they worried about breast cancer 'frequently or constantly' and 18% that worry about breast cancer was 'a severe or definite problem'. Following genetic counselling, levels of cancer-specific distress were unchanged. General mental health remained unchanged over time (33% psychiatric cases detected pre-genetic counselling, 27% at 12 months after genetic counselling). Prior to their genetics consultation, participants showed poor knowledge of their lifetime risk of breast cancer since there was no association between their perceived lifetime risk (when they were asked to express this as a 1 in x odds ratio) and their actual risk, when the latter was calculated by the geneticist at the clinic using the CASH model. In contrast, women were more accurate about their risk of breast cancer pre-genetic counselling when this was assessed in broad categorical terms (i.e. very much lower/very much higher than the average woman) with a significant association between this rating and the subsequently calculated CASH risk figure (P = 0.001). Genetic counselling produced a modest shift in the accuracy of perceived lifetime risk, expressed as an odds ratio, which was maintained at 12 months' follow-up. A significant minority failed to benefit from genetic counselling; 77 women continued to over-estimate their risk and maintain high levels of
DEFF Research Database (Denmark)
Jensen, K.K.; Gamborg, C.; Madsen, K.H.
2003-01-01
In Europe, there seems to be widespread, morally based scepticism about the use of GMOs in food production. In response to this scepticism, the revised EU directive 2001/18/EC on the deliberate release into the environment of genetically modified organisms stresses the importance of respecting...... assessment and approval of GMOs outlined in the directive. An environmental risk assessment views the world through a "risk window" that only makes visible that which has been predefined as a relevant risk. The importance of the value judgements that define the risk window consists in limiting...
Perceptions regarding genetic testing in populations at risk for nephropathy.
Freedman, Barry I; Fletcher, Alison J; Sanghani, Vivek R; Spainhour, Mitzie; Graham, Angelina W; Russell, Gregory B; Cooke Bailey, Jessica N; Iltis, Ana S; King, Nancy M P
2013-01-01
Population ancestry-based differences exist in genetic risk for many kidney diseases. Substantial debate remains regarding returning genetic test results to participants. African-Americans (AAs) and European-Americans (EAs) at risk for end-stage kidney disease were queried for views on the value and use of genetic testing in research. A standardized survey regarding attitudes toward genetic testing was administered to 130 individuals (64 AA, 66 EA) with first-degree relatives on dialysis. Fisher's exact test was used to assess differences in participant attitudes between population groups. Mean (SD) age of surveyed AAs and EAs was 45.5 (12.8) and 50.5 (14.4) years, respectively (p = 0.04), with similar familial relationships (p = 0.22). AAs and EAs wished to know their test results if risk could be: (1) reduced by diet or exercise (100 and 98%, p = 0.99); (2) reduced by medical treatment (100 and 98%, p = 0.99), or (3) if no treatments were available (90 and 82%, p = 0.21). If informed they lacked a disease susceptibility variant, 87% of AAs and 88% of EAs would be extremely or pretty likely to inform family members (p = 0.84). If informed they had a disease susceptibility variant, 92% of AAs and 89% of EAs would be extremely or pretty likely to inform their family (p = 0.43). Attitudes toward obtaining and using genetic test results for disease in research contexts were similar in AAs and EAs at risk for end-stage kidney disease. A substantial majority would want information regardless of available treatments and would share the information with the family. These results have important implications for patient care, study design and the informed consent process. © 2013 S. Karger AG, Basel.
Hilbeck, Angelika; Bundschuh, Rebecca; Bundschuh, Mirco; Hofmann, Frieder; Oehen, Bernadette; Otto, Mathias; Schulz, Ralf; Trtikova, Miluse
2017-11-01
For a long time, the environmental risk assessment (ERA) of genetically modified (GM) crops focused mainly on terrestrial ecosystems. This changed when it was scientifically established that aquatic ecosystems are exposed to GM crop residues that may negatively affect aquatic species. To assist the risk assessment process, we present a tool to identify ecologically relevant species usable in tiered testing prior to authorization or for biological monitoring in the field. The tool is derived from a selection procedure for terrestrial ecosystems with substantial but necessary changes to adequately consider the differences in the type of ecosystems. By using available information from the Water Framework Directive (2000/60/EC), the procedure can draw upon existing biological data on aquatic systems. The proposed procedure for aquatic ecosystems was tested for the first time during an expert workshop in 2013, using the cultivation of Bacillus thuringiensis (Bt) maize as the GM crop and 1 stream type as the receiving environment in the model system. During this workshop, species executing important ecological functions in aquatic environments were identified in a stepwise procedure according to predefined ecological criteria. By doing so, we demonstrated that the procedure is practicable with regard to its goal: From the initial long list of 141 potentially exposed aquatic species, 7 species and 1 genus were identified as the most suitable candidates for nontarget testing programs. Integr Environ Assess Manag 2017;13:974-979. © 2017 SETAC. © 2017 SETAC.
Quantification of the genetic risk of environmental mutagens
International Nuclear Information System (INIS)
Ehling, U.H.
1988-01-01
Screening methods are used for hazard identification. Assays for heritable mutations in mammals are used for the confirmation of short-term test results and for the quantification of the genetic risk. There are two main approaches in making genetic risk estimates. One of these, termed the direct method, expresses risk in terms of the expected frequency of genetic changes induced per unit. The other, referred to as the doubling dose method or the indirect method, expresses risk in relation to the observed incidence of genetic disorders now present in man. The indirect method uses experimental data only for the calculation of the doubling dose. The quality of the risk estimation depends on the assumption of persistence of the induced mutations and the ability to determine the current incidence of genetic diseases. The difficulties of improving the estimates of current incidences of genetic diseases or the persistence of the genes in the population led them to the development of an alternative method, the direct estimation of the genetic risk. The direct estimation uses experimental data for the induced frequency for dominant mutations in mice. For the verification of these quantifications one can use the data of Hiroshima and Nagasaki. According to the estimation with the direct method, one would expect less than 1 radiation-induced dominant cataract in 19,000 children with one or both parents exposed. The expected overall frequency of dominant mutations in the first generation would be 20-25, based on radiation-induced dominant cataract mutations. It is estimated that 10 times more recessive than dominant mutations are induced. The same approaches can be used to determine the impact of chemical mutagens
Genetically Modified Foods: Promises, Challenges and Safety Assessments
Directory of Open Access Journals (Sweden)
Manouchehr Dadgarnejad
2017-09-01
Full Text Available Background and Objective: Application of genetically modified organisms in the agriculture sector and food industry began since last years of 20th century. Since then this technology has become a central part of the broader public controversy about the advantages and safety of these products. This article has tried to review aspects of these types of organisms and foods.Results and Conclusion: Genetically modified technology has potential to overcome agricultural problems, such as biotic and abiotic issues by enhancing pests and herbicides resistance, drought tolerance, fast ripening, and finally enhancing yield and nutritional quality. Besides these revolutionary advantages, during the last decades some potential human, animal and environmental risks have been taken in account for these organisms or foods. However, no scientific evidence exists adequately about their harmful human or animal effects, and also, some new scientific and management methodologies (new technologies and regulations have been developed to mitigate the environmental risks. Some challenges such as pest adaptation are being solved by refuge technology, gene pyramiding and insertion of best-coupled primers through the known conditions reducing unintended outcomes including silencing, activation or rearrangement of non-target genome pieces. However, it does not mean that no harmful effect will happen in the future. Therefore, it is required that before release of any genetically modified crop, all requested risk assessments be performed, and then post release monitoring be done to follow the possible gene flow and prevent any potential disastrous contaminations to the food chain. Finally, it could be concluded that the safe usage of this technology, by considering all nationally and internationally accepted environmental and health safety assessment protocols, can help us to use advantages of this technology in agriculture, medicine and industry. However, more safety
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.
Edible safety requirements and assessment standards for agricultural genetically modified organisms.
Deng, Pingjian; Zhou, Xiangyang; Zhou, Peng; Du, Zhong; Hou, Hongli; Yang, Dongyan; Tan, Jianjun; Wu, Xiaojin; Zhang, Jinzhou; Yang, Yongcun; Liu, Jin; Liu, Guihua; Li, Yonghong; Liu, Jianjun; Yu, Lei; Fang, Shisong; Yang, Xiaoke
2008-05-01
This paper describes the background, principles, concepts and methods of framing the technical regulation for edible safety requirement and assessment of agricultural genetically modified organisms (agri-GMOs) for Shenzhen Special Economic Zone in the People's Republic of China. It provides a set of systematic criteria for edible safety requirements and the assessment process for agri-GMOs. First, focusing on the degree of risk and impact of different agri-GMOs, we developed hazard grades for toxicity, allergenicity, anti-nutrition effects, and unintended effects and standards for the impact type of genetic manipulation. Second, for assessing edible safety, we developed indexes and standards for different hazard grades of recipient organisms, for the influence of types of genetic manipulation and hazard grades of agri-GMOs. To evaluate the applicability of these criteria and their congruency with other safety assessment systems for GMOs applied by related organizations all over the world, we selected some agri-GMOs (soybean, maize, potato, capsicum and yeast) as cases to put through our new assessment system, and compared our results with the previous assessments. It turned out that the result of each of the cases was congruent with the original assessment.
Directory of Open Access Journals (Sweden)
S. Arpaia
2014-06-01
Full Text Available The environmental impacts of genetically modified crops is still a controversial issue in Europe. The overall risk assessment framework has recently been reinforced by the European Food Safety Authority(EFSA and its implementation requires harmonized and efficient methodologies. The EU-funded research project AMIGA − Assessing and monitoring Impacts of Genetically modified plants on Agro-ecosystems − aims to address this issue, by providing a framework that establishes protection goals and baselines for European agro-ecosystems, improves knowledge on the potential long term environmental effects of genetically modified (GM plants, tests the efficacy of the EFSA Guidance Document for the Environmental Risk Assessment, explores new strategies for post market monitoring, and provides a systematic analysis of economic aspects of Genetically Modified crops cultivation in the EU. Research focuses on ecological studies in different EU regions, the sustainability of GM crops is estimated by analysing the functional components of the agro-ecosystems and specific experimental protocols are being developed for this scope.
Cho, Hyunje G; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Assimes, Themistocles; Han, Jiali; Stefanick, Marcia; Tang, Jean Y; Sarin, Kavita Y
2018-07-01
Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk. We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women. Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset. Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma. Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort. Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Defining a safe genetically modified organism: Boundaries of scientific risk assessment
Katherine Barrett; Elisabeth Abergel
2002-01-01
The development and commercialisation of genetically modified (GM) crops continues despite persisting uncertainties regarding environmental impacts. Canada is one of the world's largest producers and exporters of GM crops. Regulators have claimed that existing federal policies for assessing environmental hazards are ‘science-based’ and sufficiently precautionary. We challenge this by examining the scientific data used to approve one variety of GM canola for environmental release. We argue tha...
Assessing and monitoring impacts of genetically modified plants on agro-ecosystems
DEFF Research Database (Denmark)
Arpaia, S.; Messéan, A.; Birch, N.A.
2014-01-01
The environmental impacts of genetically modified crops is still a controversial issue in Europe. The overall risk assessment framework has recently been reinforced by the European Food Safety Authority(EFSA) and its implementation requires harmonized and efficient methodologies. The EU-funded re...
Genetic Risk Score for Essential Hypertension and Risk of Preeclampsia.
Smith, Caitlin J; Saftlas, Audrey F; Spracklen, Cassandra N; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K
2016-01-01
Preeclampsia is a hypertensive complication of pregnancy characterized by novel onset of hypertension after 20 weeks gestation, accompanied by proteinuria. Epidemiological evidence suggests that genetic susceptibility exists for preeclampsia; however, whether preeclampsia is the result of underlying genetic risk for essential hypertension has yet to be investigated. Based on the hypertensive state that is characteristic of preeclampsia, we aimed to determine if established genetic risk scores (GRSs) for hypertension and blood pressure are associated with preeclampsia. Subjects consisted of 162 preeclamptic cases and 108 normotensive pregnant controls, all of Iowa residence. Subjects' DNA was extracted from buccal swab samples and genotyped on the Affymetrix Genome-wide Human SNP Array 6.0 (Affymetrix, Santa Clara, CA). Missing genotypes were imputed using MaCH and Minimac software. GRSs were calculated for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) using established genetic risk loci for each outcome. Regression analyses were performed to determine the association between GRS and risk of preeclampsia. These analyses were replicated in an independent US population of 516 cases and 1,097 controls of European ancestry. GRSs for hypertension, SBP, DBP, and MAP were not significantly associated with risk for preeclampsia (P > 0.189). The results of the replication analysis also yielded nonsignificant associations. GRSs for hypertension and blood pressure are not associated with preeclampsia, suggesting that an underlying predisposition to essential hypertension is not on the causal pathway of preeclampsia. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Directory of Open Access Journals (Sweden)
Cho Alex H
2012-01-01
Full Text Available Abstract Background Type 2 diabetes is a prevalent chronic condition globally that results in extensive morbidity, decreased quality of life, and increased health services utilization. Lifestyle changes can prevent the development of diabetes, but require patient engagement. Genetic risk testing might represent a new tool to increase patients' motivation for lifestyle changes. Here we describe the rationale, development, and design of a randomized controlled trial (RCT assessing the clinical and personal utility of incorporating type 2 diabetes genetic risk testing into comprehensive diabetes risk assessments performed in a primary care setting. Methods/Design Patients are recruited in the laboratory waiting areas of two primary care clinics and enrolled into one of three study arms. Those interested in genetic risk testing are randomized to receive either a standard risk assessment (SRA for type 2 diabetes incorporating conventional risk factors plus upfront disclosure of the results of genetic risk testing ("SRA+G" arm, or the SRA alone ("SRA" arm. Participants not interested in genetic risk testing will not receive the test, but will receive SRA (forming a third, "no-test" arm. Risk counseling is provided by clinic staff (not study staff external to the clinic. Fasting plasma glucose, insulin levels, body mass index (BMI, and waist circumference are measured at baseline and 12 months, as are patients' self-reported behavioral and emotional responses to diabetes risk information. Primary outcomes are changes in insulin resistance and BMI after 12 months; secondary outcomes include changes in diet patterns, physical activity, waist circumference, and perceived risk of developing diabetes. Discussion The utility, feasibility, and efficacy of providing patients with genetic risk information for common chronic diseases in primary care remain unknown. The study described here will help to establish whether providing type 2 diabetes genetic risk
Directory of Open Access Journals (Sweden)
Weigl K
2018-01-01
Full Text Available Korbinian Weigl,1,2 Jenny Chang-Claude,3,4 Phillip Knebel,5 Li Hsu,6 Michael Hoffmeister,1 Hermann Brenner1,2,7 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ, Heidelberg, 2German Cancer Consortium (DKTK, German Cancer Research Center (DKFZ, Heidelberg, 3Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ, Heidelberg, 4University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, 5Department for General, Visceral and Transplantation Surgery, University Heidelberg, Heidelberg, Germany; 6Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 7Division of Preventive Oncology, German Cancer Research Center (DKFZ and National Center for Tumor Diseases (NCT, Heidelberg, Germany Background and aim: Family history (FH and genetic risk scores (GRSs are increasingly used for risk stratification for colorectal cancer (CRC screening. However, they were mostly considered alternatively rather than jointly. The aim of this study was to assess the potential of individual and joint risk stratification for CRC by FH and GRS.Patients and methods: A GRS was built based on the number of risk alleles in 53 previously identified single-nucleotide polymorphisms among 2,363 patients with a first diagnosis of CRC and 2,198 controls in DACHS [colorectal cancer: chances for prevention through screening], a population-based case-control study in Germany. Associations between GRS and FH with CRC risk were quantified by multiple logistic regression.Results: A total of 316 cases (13.4% and 214 controls (9.7% had a first-degree relative (FDR with CRC (adjusted odds ratio [aOR] 1.86, 95% CI 1.52–2.29. A GRS in the highest decile was associated with a 3.0-fold increased risk of CRC (aOR 3.00, 95% CI 2.24–4.02 compared with the lowest decile. This association was tentatively more pronounced in older age groups. FH and GRS were essentially unrelated, and their
Challenges in Risk Assessment: Quantitative Risk Assessment
Jacxsens, Liesbeth; Uyttendaele, Mieke; De Meulenaer, Bruno
2016-01-01
The process of risk analysis consists out of three components, risk assessment, risk management and risk communication. These components are internationally well spread by Codex Alimentarius Commission as being the basis for setting science based standards, criteria on food safety hazards, e.g. setting maximum limits of mycotoxins in foodstuffs. However, the technical component risk assessment is hard to elaborate and to understand. Key in a risk assessment is the translation of biological or...
Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.
Abdullah, N; Abdul Murad, N A; Attia, J; Oldmeadow, C; Mohd Haniff, E A; Syafruddin, S E; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G
2015-10-01
To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.
Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina
2015-03-01
The authors sought to clarify the relationship between IQ and subsequent risk for schizophrenia. IQ was assessed at ages 18-20 in 1,204,983 Swedish males born between 1951 and 1975. Schizophrenia was assessed by hospital diagnosis through 2010. Cox proportional hazards models were used to investigate future risk for schizophrenia in individuals as a function of their IQ score, and then stratified models using pairs of relatives were used to adjust for familial cluster. Finally, regression models were used to examine the interaction between IQ and genetic liability on risk for schizophrenia. IQ had a monotonic relationship with schizophrenia risk across the IQ range, with a mean increase in risk of 3.8% per 1-point decrease in IQ; this association was stronger in the lower than the higher IQ range. Co-relative control analyses showed a similar association between IQ and schizophrenia in the general population and in cousin, half-sibling, and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low than high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses showed that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia.
Assessing environmental impacts of genetically modified plants on non-target organisms
Arpaia, Salvatore; Birch, A.N.E.; Kiss, Jozsef; Loon, van Joop J.A.; Messéan, Antoine; Nuti, Marco; Perry, Joe N.; Sweet, Jeremy B.; Tebbe, Christoph C.
2017-01-01
In legal frameworks worldwide, genetically modified plants (GMPs) are subjected to pre-market environmental risk assessment (ERA) with the aim of identifying potential effects on the environment. In the European Union, the EFSA Guidance Document introduces the rationale that GMPs, as well as their
Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L; Hayden, Michael R
2009-06-09
To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested. Cross sectional, self reported survey. Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. 233 genetically tested and untested asymptomatic people at risk for Huntington's disease (response rate 80%): 167 underwent testing (83 had the Huntington's disease mutation, 84 did not) and 66 chose not to be tested. Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington's disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington's disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (PGenetic discrimination was commonly reported by people at risk for Huntington's disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination.
Personalized Genetic Risk Counseling to Motivate Diabetes Prevention: A randomized trial
Grant, Richard W.; O’Brien, Kelsey E.; Waxler, Jessica L.; Vassy, Jason L.; Delahanty, Linda M.; Bissett, Laurie G.; Green, Robert C.; Stember, Katherine G.; Guiducci, Candace; Park, Elyse R.; Florez, Jose C.; Meigs, James B.
2013-01-01
OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top an...
Systematic assessment of environmental risk factors for bipolar disorder
DEFF Research Database (Denmark)
Bortolato, Beatrice; Köhler, Cristiano A.; Evangelou, Evangelos
2017-01-01
factors supported by high epidemiological credibility. Methods: We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases up to 7 October 2016 to identify systematic reviews and meta-analyses of observational studies that assessed associations between putative environmental risk factors and BD......Objectives: The pathophysiology of bipolar disorder is likely to involve both genetic and environmental risk factors. In our study, we aimed to perform a systematic search of environmental risk factors for BD. In addition, we assessed possible hints of bias in this literature, and identified risk...... met the inclusion criteria (seven meta-analyses and nine qualitative systematic reviews). Fifty-one unique environmental risk factors for BD were evaluated. Six meta-analyses investigated associations with a risk factor for BD. Only irritable bowel syndrome (IBS) emerged as a risk factor for BD...
Environmental chemical mutagens and genetic risks: Lessons from radiation genetics
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1996-01-01
The last three decades have witnessed substantial progress in the development and use of a variety of in vitro and in vivo assay systems for the testing of environmental chemicals which may pose a mutagenic hazard to humans. This is also true of basic studies in chemical mutagenesis on mechanisms, DNA repair, molecular dosimetry, structure-activity relationships, etc. However, the field of quantitative evaluation of genetic risks of environmental chemicals to humans is still in it infancy. This commentary addresses the question of how our experience in estimating genetic risks of exposure to ionizing radiation can be helpful in similar endeavors with environmental chemical mutagens. 24 refs., 3 tabs
Directory of Open Access Journals (Sweden)
Rahul S Desikan
2017-03-01
Full Text Available Identifying individuals at risk for developing Alzheimer disease (AD is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction.Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1, we identified AD-associated SNPs (at p < 10-5. We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer's Disease Genetics Consortium (ADGC, providing a polygenic hazard score (PHS for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer's Disease Center [NIA ADC], and Alzheimer's Disease Neuroimaging Initiative [ADNI], total n = 20,680. Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62-4.24, p = 1.0 × 10-22. In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10-26 and longitudinal progression from normal aging to AD (NIA ADC, Cochran-Armitage trend test, p = 1.5 × 10-10, and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10-6, and Consortium to Establish a Registry for Alzheimer's Disease score for neuritic plaques, p = 6.8 × 10-6 and in vivo markers of AD neurodegeneration (ADNI
Integrated genomic and BMI analysis for type 2 diabetes risk assessment.
Directory of Open Access Journals (Sweden)
Dayanara eLebrón-Aldea
2015-03-01
Full Text Available Type 2 Diabetes (T2D is a chronic disease arising from the development of insulin absence or resistance within the body, and a complex interplay of environmental and genetic factors. The incidence of T2D has increased throughout the last few decades, together with the occurrence of the obesity epidemic. The consideration of variants identified by Genome Wide Association Studies (GWAS into risk assessment models for T2D could aid in the identification of at-risk patients who could benefit from preventive medicine. In this study, we build several risk assessment models, and evaluated them with two different classification approaches (Logistic Regression and Neural Networks, to measure the effect of including genetic information in the prediction of T2D. We used data from to the Original and the Offspring cohorts of the Framingham Heart Study, which provides phenotypic and genetic information for 5,245 subjects (4,306 controls and 939 cases. Models were built by using several covariates: gender, exposure time, cohort, body mass index (BMI, and 65 established T2D-associated SNPs. We fitted Logistic Regressions and Bayesian Regularized Neural Network and then assessed their predictive ability by using a ten-fold cross validation. We found that the inclusion of genetic information into the risk assessment models increased the predictive ability by 2%, when compared to the baseline model. Furthermore, the models that included BMI at the onset of diabetes as a possible effector, gave an improvement of 6% in the area under the curve derived from the ROC analysis. The highest AUC achieved (0.75 belonged to the model that included BMI, and a genetic score based on the 65 established T2D-associated SNPs. Finally, the inclusion of SNPs and BMI raised predictive ability in all models as expected; however, results from the AUC in Neural Networks and Logistic Regression did not differ significantly in their prediction accuracy.
Myers, Ronald E.; Manne, Sharon L.; Wilfond, Benjamin; Sifri, Randa; Ziring, Barry; Wolf, Thomas A.; Cocroft, James; Ueland, Amy; Petrich, Anett; Swan, Heidi; DiCarlo, Melissa; Weinberg, David S.
2010-01-01
Purpose This paper describes an ongoing randomized controlled trial designed to assess the impact of genetic and environmental risk assessment (GERA) on colorectal cancer (CRC) screening. Methods The trial includes asymptomatic patients who are 50-79 years and are not up-to-date with CRC screening guidelines. Patients who responded to a baseline telephone survey are randomized to a GERA or Control group. GERA Group participants meet with a nurse, decide whether to have a GERA blood test (a combination of genetic polymorphism and folate), and, if tested, receive GERA feedback. Follow-up telephone surveys are conducted at one and six months. A chart audit is performed at six months. Results Of 2,223 eligible patients, 562 (25%) have enrolled. Patients who enrolled in the study were significantly younger than those who did not (p<0.001). Participants tended to be 50-59 years (64%), female (58%), white (52%), married (51%), and have more than a high school education (67%). At baseline, most participants had some knowledge of CRC screening and GERA, viewed CRC screening favorably, and reported that they had decided to do screening. Almost half had worries and concerns about CRC. Conclusions One in four eligible primary care patients enrolled in the study. Age was negatively associated with enrollment. Prospective analyses using data for all participants will provide more definitive information on GERA uptake and the impact of GERA feedback. PMID:20828635
Mets, Sarah; Tryon, Rebecca; Veach, Patricia McCarthy; Zierhut, Heather A
2016-04-01
The development of hereditary cancer genetic testing panels has altered genetic counseling practice. Mutations within certain genes on cancer panels pose not only a cancer risk, but also a reproductive risk for autosomal recessive conditions such as Fanconi anemia, constitutional mismatch repair deficiency syndrome, and ataxia telangiectasia. This study aimed to determine if genetic counselors discuss reproductive risks for autosomal recessive conditions associated with genes included on cancer panels, and if so, under what circumstances these risks are discussed. An on-line survey was emailed through the NSGC list-serv. The survey assessed 189 cancer genetic counselors' experiences discussing reproductive risks with patients at risk to carry a mutation or variant of uncertain significance (VUS) in a gene associated with both an autosomal dominant cancer risk and an autosomal recessive syndrome. Over half (n = 82, 55 %) reported having discussed reproductive risks; the remainder (n = 66, 45 %) had not. Genetic counselors who reported discussing reproductive risks primarily did so when patients had a positive result and were of reproductive age. Reasons for not discussing these risks included when a patient had completed childbearing or when a VUS was identified. Most counselors discussed reproductive risk after obtaining results and not during the informed consent process. There is inconsistency as to if and when the discussion of reproductive risks is taking place. The wide variation in responses suggests a need to develop professional guidelines for when and how discussions of reproductive risk for autosomal recessive conditions identified through cancer panels should occur with patients.
Health effects of low-level ionising radiation: biological basis for risk assessment
International Nuclear Information System (INIS)
Upton, A.C.
1987-01-01
The biological basis for risk assessment is discussed. The risks of carcinogenic effects, teratogenic effects, and genetic (heritable) effects are estimated to vary in proportion with the dose of radiation in the low-dose domain; however, the risks also appear to vary with the LET of the radiation, age at the time of irradiation, and other variables. Although the data suffice to place the risks in perspective with other hazards of modern life, further research to refine the reliability of the risk assessment is called for. (author)
Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J
2014-08-01
The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.
Kim, Jihye; Kraft, Peter; Hagan, Kaitlin A; Harrington, Laura B; Lindstroem, Sara; Kabrhel, Christopher
2018-06-01
Venous thromboembolism (VTE) is highly heritable. Physical activity, physical inactivity and body mass index (BMI) are also risk factors, but evidence of interaction between genetic and environmental risk factors is limited. Data on 2,134 VTE cases and 3,890 matched controls were obtained from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and Health Professionals Follow-up Study (HPFS). We calculated a weighted genetic risk score (wGRS) using 16 single nucleotide polymorphisms associated with VTE risk in published genome-wide association studies (GWAS). Data on three risk factors, physical activity (metabolic equivalent [MET] hours per week), physical inactivity (sitting hours per week) and BMI, were obtained from biennial questionnaires. VTE cases were incident since cohort inception; controls were matched to cases on age, cohort, and genotype array. Using conditional logistic regression, we assessed joint effects and interaction effects on both additive and multiplicative scales. We also ran models using continuous wGRS stratified by risk-factor categories. We observed a supra-additive interaction between wGRS and BMI. Having both high wGRS and high BMI was associated with a 3.4-fold greater risk of VTE (relative excess risk due to interaction = 0.69, p = 0.046). However, we did not find evidence for a multiplicative interaction with BMI. No interactions were observed for physical activity or inactivity. We found a synergetic effect between a genetic risk score and high BMI on the risk of VTE. Intervention efforts lowering BMI to decrease VTE risk may have particularly large beneficial effects among individuals with high genetic risk. © 2018 WILEY PERIODICALS, INC.
Nuotio, Joel; Pitkänen, Niina; Magnussen, Costan G; Buscot, Marie-Jeanne; Venäläinen, Mikko S; Elo, Laura L; Jokinen, Eero; Laitinen, Tomi; Taittonen, Leena; Hutri-Kähönen, Nina; Lyytikäinen, Leo-Pekka; Lehtimäki, Terho; Viikari, Jorma S; Juonala, Markus; Raitakari, Olli T
2017-06-01
Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures. Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3-18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; P =0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; P dyslipidemia in adulthood. © 2017 American Heart Association, Inc.
A risk-based classification scheme for genetically modified foods. I: Conceptual development.
Chao, Eunice; Krewski, Daniel
2008-12-01
The predominant paradigm for the premarket assessment of genetically modified (GM) foods reflects heightened public concern by focusing on foods modified by recombinant deoxyribonucleic acid (rDNA) techniques, while foods modified by other methods of genetic modification are generally not assessed for safety. To determine whether a GM product requires less or more regulatory oversight and testing, we developed and evaluated a risk-based classification scheme (RBCS) for crop-derived GM foods. The results of this research are presented in three papers. This paper describes the conceptual development of the proposed RBCS that focuses on two categories of adverse health effects: (1) toxic and antinutritional effects, and (2) allergenic effects. The factors that may affect the level of potential health risks of GM foods are identified. For each factor identified, criteria for differentiating health risk potential are developed. The extent to which a GM food satisfies applicable criteria for each factor is rated separately. A concern level for each category of health effects is then determined by aggregating the ratings for the factors using predetermined aggregation rules. An overview of the proposed scheme is presented, as well as the application of the scheme to a hypothetical GM food.
Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.
2011-01-01
Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497
Safety assessment of genetically modified crops
International Nuclear Information System (INIS)
Atherton, Keith T.
2002-01-01
The development of genetically modified (GM) crops has prompted widespread debate regarding both human safety and environmental issues. Food crops produced by modern biotechnology using recombinant techniques usually differ from their conventional counterparts only in respect of one or a few desirable genes, as opposed to the use of traditional breeding methods which mix thousands of genes and require considerable efforts to select acceptable and robust hybrid offspring. The difficulties of applying traditional toxicological testing and risk assessment procedures to whole foods are discussed along with the evaluation strategies that are used for these new food products to ensure the safety of these products for the consumer
New approaches in human health risk assessment.
Abass, Khaled; Carlsen, Anders; Rautio, Arja
2016-01-01
Studies on the precise impact of environmental pollutants on human health are difficult to undertake and interpret, because many genetic and environmental factors influence health at the same time and to varying degrees. Our chapter in the AMAP report was based on new approaches to describe risks and future needs. In this paper, we will introduce the issues associated with risk assessment of single chemicals, and present suggestions for future studies as well as a summary of lessons learned during the health-related parts of the European Union-funded FP7 project ArcRisk (Arctic Health Risks: Impacts on health in the Arctic and Europe owing to climate-induced changes in contaminant cycling, 2009-2014; www.arcrisk.eu).
Wu, Yelena P; Mays, Darren; Kohlmann, Wendy; Tercyak, Kenneth P
2017-10-01
Predispositional genetic testing among minor children is intensely debated due to the potential benefits and harms of providing this type of genetic information to children and their families. Existing guidelines on pediatric genetic testing state that predispositional testing could be appropriate for minors if preventive services exist that mitigate children's risk for or severity of the health condition in question. We use the example of hereditary melanoma to illustrate the rationale for and potential application of genetic risk communication for an adult-onset cancer to a pediatric population where childhood behaviors may reduce risk of disease later in life. We draw from the adult melanoma genetic risk communication and pediatric health behavior change literatures to suggest ways in which genetic test reporting and complementary education could be delivered to children who carry a hereditary risk for melanoma and their families in order to foster children's engagement in melanoma preventive behaviors. Genetic discoveries will continue to yield new opportunities to provide predispositional genetic risk information to unaffected individuals, including children, and could be delivered within programs that provide personalized and translational approaches to cancer prevention.
Varzakas, Theodoros H; Chryssochoidis, G; Argyropoulos, D
2007-04-01
Risk analysis has become important to assess conditions and take decisions on control procedures. In this context it is considered a prerequisite in the evaluation of GM food. Many consumers worldwide worry that food derived from genetically modified organisms (GMOs) may be unhealthy and hence regulations on GMO authorisations and labelling have become more stringent. Nowadays there is a higher demand for non-GM products and these products could be differentiated from GM products using the identity preservation system (IP) that could apply throughout the grain processing system. IP is the creation of a transparent communication system that encompasses HACCP, traceability and related systems in the supply chain. This process guarantees that certain characteristics of the lots of food (non-GM origin) are maintained "from farm to fork". This article examines the steps taken by the Hellenic Food Safety Authority to examine the presence of GMOs in foods. The whole integrated European legislation framework currently in place still needs to be implemented in Greece. Penalties should be enforced to those who import, process GMOs without special licence and do not label those products. Similar penalties should be enforced to those companies that issue false certificates beyond the liabilities taken by the food enterprises for farmers' compensation. We argue that Greece has no serious reasons to choose the use of GMOs due to the fact that the structural and pedologic characteristics of the Greek agriculture favour the biological and integrated cultivation more. Greece is not in favour of the politics behind coexistence of conventional and GM plants and objects to the use of GMOs in the food and the environment because the processor has a big burden in terms of money, time and will suffer a great deal in order to prove that their products are GMO free or that any contamination is adventitious or technically unavoidable. Moreover, Greece owns a large variety of genetic
Anorexia nervosa and major depression: shared genetic and environmental risk factors.
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.
Risk assessment in man and mouse.
Balci, Fuat; Freestone, David; Gallistel, Charles R
2009-02-17
Human and mouse subjects tried to anticipate at which of 2 locations a reward would appear. On a randomly scheduled fraction of the trials, it appeared with a short latency at one location; on the complementary fraction, it appeared after a longer latency at the other location. Subjects of both species accurately assessed the exogenous uncertainty (the probability of a short versus a long trial) and the endogenous uncertainty (from the scalar variability in their estimates of an elapsed duration) to compute the optimal target latency for a switch from the short- to the long-latency location. The optimal latency was arrived at so rapidly that there was no reliably discernible improvement over trials. Under these nonverbal conditions, humans and mice accurately assess risks and behave nearly optimally. That this capacity is well-developed in the mouse opens up the possibility of a genetic approach to the neurobiological mechanisms underlying risk assessment.
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.
Ionizing radiation, genetic risks and radiation protection
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1992-01-01
With one method of risk estimation, designed as the doubling dose method, the estimates of total genetic risk (i.e., over all generation) for a population continuously exposed at a rate of 0.01 Gy/generation of low LET irradiation are about 120 cases of Mendelian and chromosomal diseases/10 6 live births and about the same number of cases for multifactorial diseases (i.e., a total of 240 cases/10 6 ). These estimates provide the basis for risk coefficients for genetic effects estimated by ICRP (1991) in its Publication 60. These are: 1.0%/Sv for the general population (which is 40% of 240/10 6 /0.01 Gy), and 0.6%/Sv for radiation workers (which is 60% of that for the general population). The results of genetic studies carried out on the Japanese survivors of A-bombs have shown no significant adverse effects attributable to parental radiation exposures. The studies of Gardner and colleagues suggest that the risk of leukaemia in children born to male workers in the nuclear reprocessing facility in Sellafield, U.K., may be increased. However, this finding is at variance with the results from the Japanese studies and at present, does not lend itself to a simple interpretation based on radiobiological principles. In the light of recent advances in the molecular biology of naturally-occurring human Mendelian diseases and what we presently know about multifactorial diseases, arguments are advanced to support the thesis that (i) current risk estimates for Mendelian diseases may be conservative and (ii) an overall doubling dose for all adverse genetic effects may be higher than the 1 Gy currently used (i.e., the relative risks are probably lower). (author)
Directory of Open Access Journals (Sweden)
Anders Borglykke
Full Text Available To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint.Data from the first Danish MONICA study (N = 3523 and the Inter99 study (N = 6049 was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR per risk allele.During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years. In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027-1.283 , P = 0.0154, C2CD4A rs7172432 (1.112, 1.027-1.205 , P = 0.0089, GCKR rs780094 (1.094, 1.007-1.188 , P = 0.0335 and C2CD4B rs11071657 (1.092, 1.007-1.183 , P = 0.0323. The genetic score was significantly associated with increased risk of CVD (1.025, 1.010-1.041, P = 0.0016. In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038-1.341 P = 0.0116 and FTO (0.909, 0.827-0.998, P = 0.0463. Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070-1.267, P = 0.0004 meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010-1.146, P = 0.0229, C2CD4B rs11071657 (1.067, 1.003-1.135, P = 0.0385 and NOTCH2 rs10923931 (1.104 (1.001 ; 1.217 , P = 0.0481 were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006-1.031, P = 0.0043.This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005 associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for
New approaches in human health risk assessment
Directory of Open Access Journals (Sweden)
Khaled Abass
2016-12-01
Full Text Available Studies on the precise impact of environmental pollutants on human health are difficult to undertake and interpret, because many genetic and environmental factors influence health at the same time and to varying degrees. Our chapter in the AMAP report was based on new approaches to describe risks and future needs. In this paper, we will introduce the issues associated with risk assessment of single chemicals, and present suggestions for future studies as well as a summary of lessons learned during the health-related parts of the European Union-funded FP7 project ArcRisk (Arctic Health Risks: Impacts on health in the Arctic and Europe owing to climate-induced changes in contaminant cycling, 2009–2014; www.arcrisk.eu.
Cancer Genetics Services Directory
... Services Directory Cancer Prevention Overview Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, ...
Taber, Jennifer M; Klein, William M P; Persky, Susan; Ferrer, Rebecca A; Kaufman, Annette R; Thai, Chan L; Harris, Peter R
2017-10-01
Implicit theories reflect core assumptions about whether human attributes are malleable or fixed: Incremental theorists believe a characteristic is malleable whereas entity theorists believe it is fixed. People with entity theories about health may be less likely to engage in risk-mitigating behavior. Spontaneous self-affirmation (e.g., reflecting on one's values when threatened) may lessen defensiveness and unhealthy behaviors associated with fixed beliefs, and reduce the likelihood of responding to health risk information with fixed beliefs. Across two studies conducted in the US from 2012 to 2015, we investigated how self-affirmation and implicit theories about health and body weight were linked to engagement with genetic risk information. In Study 1, participants in a genome sequencing trial (n = 511) completed cross-sectional assessments of implicit theories, self-affirmation, and intentions to learn, share, and use genetic information. In Study 2, overweight women (n = 197) were randomized to receive genetic or behavioral explanations for weight; participants completed surveys assessing implicit theories, self-affirmation, self-efficacy, motivation, and intentions. Fixed beliefs about weight were infrequently endorsed across studies (10.8-15.2%). In Study 1, participants with stronger fixed theories were less interested in learning and using genetic risk information about medically actionable disease; these associations were weaker among participants higher in self-affirmation. In Study 2, among participants given behavioral explanations for weight, stronger fixed theories about weight were associated with lower motivation and intentions to eat a healthy diet. Among participants given genetic explanations, being higher in self-affirmation was associated with less fixed beliefs. Stronger health-related fixed theories may decrease the likelihood of benefiting from genetic information, but less so for people who self-affirm. Published by Elsevier Ltd.
International Nuclear Information System (INIS)
Brackley, M.E.; Curry, J.; Glickman, B.W.
1999-01-01
We discuss the relevance to space medicine of studies concerning human genetic variation and consequent variable disease susceptibility or sensitivity between individuals. The size of astronaut and cosmonaut populations is both presently and cumulatively small, and despite the launch of the International Space Station, unlikely to increase by orders of magnitude within the foreseeable future. In addition, astronauts-cosmonauts constitute unrepresentative samples of their national populations. While the context of exposure for the astronaut-cosmonaut group is one unlikely to be replicated elsewhere than in space, aspects of specific exposures may be simulated by events such as occupational radiation exposure or radiation therapy. Hence, population-based studies of genetic susceptibility or sensitivity to disease, especially where it is precipitated by events that may simulate consequences of the space environment, likely will prove of value in assessing long-term health risks
Bombard, Yvonne; Veenstra, Gerry; Friedman, Jan M; Creighton, Susan; Currie, Lauren; Paulsen, Jane S; Bottorff, Joan L
2009-01-01
Objective To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington’s disease who had undergone genetic testing or remained untested. Design Cross sectional, self reported survey. Setting Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. Participants 233 genetically tested and untested asymptomatic people at risk for Huntington’s disease (response rate 80%): 167 underwent testing (83 had the Huntington’s disease mutation, 84 did not) and 66 chose not to be tested. Main outcome measures Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. Results Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington’s disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington’s disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (PGenetic discrimination was commonly reported by people at risk for Huntington’s disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination. PMID:19509425
Medical radiation exposure and genetic risks
International Nuclear Information System (INIS)
Baker, D.G.
1980-01-01
Everyone is exposed to background radiation throughout life (100 mrem/year to the gonads or 4 to 5 rem during the reproductive years). A lumbosacral series might deliver 2500 mrem to the male or 400 mrem to the female gonads. A radiologic procedure is a cost/benefit decision, and genetic risk is a part of the cost. Although cost is usually very low compared to benefit, if the procedure is unnecessary then the cost may be unacceptable. On the basis of current estimates, the doubling dose is assumed to be 40 rem (range 20 to 200) for an acute dose, and 100 rem for protracted exposure. Although there is no satisfactory way to predict the size of the risk for an individual exposed, any risk should be incentive to avoid unnecessary radiation to the gonads. Conception should be delayed for at least ten months for women and three or four months for men after irradiation of the gonads. The current incidence of genetically related diseases in the United States population is 60,000 per million live births. Based on the most conservative set of assumptions, an average gonadal dose of 1000 mrem to the whole population would increase the incidence of genetically related diseases by 0.2%
Precision Oncology and Genetic Risk Information: Exploring Patients' Preferences and Responses
Dr. Jada Hamilton is an Assistant Member at Memorial Sloan Kettering Cancer Center, as well as an Assistant Attending Psychologist in the Behavioral Sciences Service, Department of Psychiatry and Behavioral Sciences and in the Clinical Genetics Service, Department of Medicine at Memorial Hospital in New York, New York. She leads a program of research at the intersection of behavioral science, cancer prevention, and genomics, with the goal of translating advances in genetic and genomic medicine into improved cancer care that is of high quality, aligned with patient preferences, and ultimately improves public health. Dr. Hamilton is also currently leading a study to assess how patients and their families respond to inherited risk information that is revealed as part of tumor sequencing (funded through a Mentored Research Scholar Grant from the American Cancer Society), as well as studies to evaluate alternative models for offering genetic counseling and testing to patients with cancer, and to examine the effects of novel breast cancer genetic risk feedback on patients’ decision-making, psychological, and behavioral outcomes. Prior to joining the faculty of Memorial Sloan Kettering, Dr. Hamilton received a BA in Genetics and Psychology from Ohio Wesleyan University (2004), an MA and PhD in Social and Health Psychology from Stony Brook University (2006, 2009), and an MPH from the Mailman School of Public Health at Columbia University (2010). She also completed a postdoctoral fellowship as part of the National Cancer Institute’s Cancer Prevention Fellowship Program.
How does genetic risk information for Lynch syndrome translate to risk management behaviours?
Steel, Emma; Robbins, Andrew; Jenkins, Mark; Flander, Louisa; Gaff, Clara; Keogh, Louise
2017-01-01
There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. Thirty-three people were interviewed. Of the non-carriers ( n = 16), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers ( n = 17), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure's ability to reduce their risk of developing colorectal cancer. Of the female carriers ( n = 9), 2 could not recall being informed about the associated risk of gynaecological cancers. Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome.
Genetic effects of ionising radiation in man
International Nuclear Information System (INIS)
Sankaranarayanan, K.
1991-01-01
A review is given of genetic risk estimation in man. Topics covered include the methods used, the germ cell stages and radiation conditions relevant for genetic risk estimation, doubling dose estimates, the classification and prevalence of naturally-occurring genetic disorders, the source of data used in the direct method of risk estimation, the genetic risk estimates from the mid-1970s to the present, the estimates of genetic risk used in ICRP 26 in 1977 and ICRP's current assessment of genetic risks. (UK)
Individualized fracture risk assessment: State-of-the-art and room for improvement
Directory of Open Access Journals (Sweden)
Tuan V. Nguyen
2018-03-01
Full Text Available Fragility fracture is a serious clinical event, because it is associated with increased risk of mortality and reduced quality of life. The risk of fracture is determined by multiple risk factors, and their effects may be interactional. Over the past 10 years, a number of predictive models (e.g., FRAX, Garvan Fracture Risk Calculator, and Qfracture have been developed for individualized assessment of fracture risk. These models use different risk profiles to estimate the probability of fracture over 5- and 10-year period. The ability of these models to discriminate between those individuals who will and will not have a fracture (i.e., area under the receiver operating characteristic curve [AUC] is generally acceptable-to-good (AUC, 0.6 to 0.8, and is highly variable between populations. The calibration of existing models is poor, particularly in Asian populations. There is a strong need for the development and validation of new prediction models based on Asian data for Asian populations. We propose approaches to improve the accuracy of existing predictive models by incorporating new markers such as genetic factors, bone turnover markers, trabecular bone score, and time-variant factors. New and more refined models for individualized fracture risk assessment will help identify those most likely to sustain a fracture, those most likely to benefit from treatment, and encouraging them to modify their risk profile to decrease risk. Keywords: Osteoporosis, Fracture, Fracture risk assessment, Genetic profiling, FRAX, Garvan
Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.
Spracklen, Cassandra N; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K
2015-07-01
Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Häggman, Hely; Raybould, Alan; Borem, Aluizio; Fox, Thomas; Handley, Levis; Hertzberg, Magnus; Lu, Meng-Zu; Macdonald, Philip; Oguchi, Taichi; Pasquali, Giancarlo; Pearson, Les; Peter, Gary; Quemada, Hector; Séguin, Armand; Tattersall, Kylie; Ulian, Eugênio; Walter, Christian; McLean, Morven
2013-09-01
Forests are vital to the world's ecological, social, cultural and economic well-being yet sustainable provision of goods and services from forests is increasingly challenged by pressures such as growing demand for wood and other forest products, land conversion and degradation, and climate change. Intensively managed, highly productive forestry incorporating the most advanced methods for tree breeding, including the application of genetic engineering (GE), has tremendous potential for producing more wood on less land. However, the deployment of GE trees in plantation forests is a controversial topic and concerns have been particularly expressed about potential harms to the environment. This paper, prepared by an international group of experts in silviculture, forest tree breeding, forest biotechnology and environmental risk assessment (ERA) that met in April 2012, examines how the ERA paradigm used for GE crop plants may be applied to GE trees for use in plantation forests. It emphasizes the importance of differentiating between ERA for confined field trials of GE trees, and ERA for unconfined or commercial-scale releases. In the case of the latter, particular attention is paid to characteristics of forest trees that distinguish them from shorter-lived plant species, the temporal and spatial scale of forests, and the biodiversity of the plantation forest as a receiving environment. © 2013 ILSI Research Foundation. Plant Biotechnology Journal published by Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.
Coverage of endangered species in environmental risk assessments at EFSA
Brock, T.C.M.
2016-01-01
The EFSA performs environmental risk assessment (ERA) for single potential stressors such as plant protection products, genetically modified organisms and feed additives, and for invasive alien species that are harmful to plant health. This ERA focusses primarily on the use or spread of such
Can systematic reviews inform GMO risk assessment and risk management?
Directory of Open Access Journals (Sweden)
Christian eKohl
2015-08-01
Full Text Available Systematic reviews represent powerful tools to identify, collect, synthesize and evaluate primary research data on specific research questions in a highly standardized and reproducible manner. They enable the defensible synthesis of outcomes by increasing precision and minimizing bias whilst ensuring transparency of the methods used. This makes them especially valuable to inform evidence-based risk analysis and decision making in various topics and research disciplines. Although seen as a gold standard for synthesizing primary research data, systematic reviews are not without limitations as they are often cost, labor and time intensive and the utility of synthesis outcomes depends upon the availability of sufficient and robust primary research data. In this paper we 1 consider the added value systematic reviews could provide when synthesizing primary research data on genetically modified organisms (GMO and 2 critically assess the adequacy and feasibility of systematic review for collating and analyzing data on potential impacts of GMOs in order to better inform specific steps within GMO risk assessment and risk management. The regulatory framework of the EU is used as an example, although the issues we discuss are likely to be more widely applicable.
Can Systematic Reviews Inform GMO Risk Assessment and Risk Management?
Kohl, Christian; Frampton, Geoff; Sweet, Jeremy; Spök, Armin; Haddaway, Neal Robert; Wilhelm, Ralf; Unger, Stefan; Schiemann, Joachim
2015-01-01
Systematic reviews represent powerful tools to identify, collect, synthesize, and evaluate primary research data on specific research questions in a highly standardized and reproducible manner. They enable the defensible synthesis of outcomes by increasing precision and minimizing bias whilst ensuring transparency of the methods used. This makes them especially valuable to inform evidence-based risk analysis and decision making in various topics and research disciplines. Although seen as a "gold standard" for synthesizing primary research data, systematic reviews are not without limitations as they are often cost, labor and time intensive and the utility of synthesis outcomes depends upon the availability of sufficient and robust primary research data. In this paper, we (1) consider the added value systematic reviews could provide when synthesizing primary research data on genetically modified organisms (GMO) and (2) critically assess the adequacy and feasibility of systematic review for collating and analyzing data on potential impacts of GMOs in order to better inform specific steps within GMO risk assessment and risk management. The regulatory framework of the EU is used as an example, although the issues we discuss are likely to be more widely applicable.
Bundschuh, Rebecca; Kuhn, Ulrike; Bundschuh, Mirco; Naegele, Caroline; Elsaesser, David; Schlechtriemen, Ulrich; Oehen, Bernadette; Hilbeck, Angelika; Otto, Mathias; Schulz, Ralf; Hofmann, Frieder
2016-03-15
Crop plant residues may enter aquatic ecosystems via wind deposition or surface runoff. In the case of genetically modified crops or crops treated with systemic pesticides, these materials may contain insecticidal Bt toxins or pesticides that potentially affect aquatic life. However, the particular exposure pattern of aquatic ecosystems (i.e., via plant material) is not properly reflected in current risk assessment schemes, which primarily focus on waterborne toxicity and not on plant material as the route of uptake. To assist in risk assessment, the present study proposes a prioritization procedure of stream types based on the freshwater network and crop-specific cultivation data using maize in Germany as a model system. To identify stream types with a high probability of receiving crop materials, we developed a formalized, criteria-based and thus transparent procedure that considers the exposure-related parameters, ecological status--an estimate of the diversity and potential vulnerability of local communities towards anthropogenic stress--and availability of uncontaminated reference sections. By applying the procedure to maize, ten stream types out of 38 are expected to be the most relevant if the ecological effects from plant-incorporated pesticides need to be evaluated. This information is an important first step to identifying habitats within these stream types with a high probability of receiving crop plant material at a more local scale, including accumulation areas. Moreover, the prioritization procedure developed in the present study may support the selection of aquatic species for ecotoxicological testing based on their probability of occurrence in stream types having a higher chance of exposure. Finally, this procedure can be adapted to any geographical region or crop of interest and is, therefore, a valuable tool for a site-specific risk assessment of crop plants carrying systemic pesticides or novel proteins, such as insecticidal Bt toxins, expressed
Genetic testing and your cancer risk
... patientinstructions/000842.htm Genetic testing and your cancer risk To use the sharing features on this page, ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...
Colorectal Cancer Risk Assessment Tool
... 11/12/2014 Risk Calculator About the Tool Colorectal Cancer Risk Factors Download SAS and Gauss Code Page ... Rectal Cancer: Prevention, Genetics, Causes Tests to Detect Colorectal Cancer and Polyps Cancer Risk Prediction Resources Update November ...
International Nuclear Information System (INIS)
Selby, P.B.
1979-01-01
Recently two widely-recognized committees, namely the UNSCEAR and BEIR Committees, have reevaluated their estimates of genetic risks from radiation. Their estimates for gene mutations are based on two different approaches, one being the doubling-dose approach and the other being a new direct approach based on an empirical determination of the amount of dominant induced damage in the skeletons of mice in the first generation following irradiation. The estimates made by these committees are in reasonably good agreement and suggest that the genetic risks from present exposures resulting from nuclear power production are small. There is room for much improvement in the reliability of the risk estimates. The relatively new approach of measuring the amount of induced damage to the mouse skeleton shows great promise of improving knowledge about how changes in the mutation frequency affect the incidence of genetic disorders. Such findings may have considerable influence on genetic risk estimates for radiation and on the development of risk estimates for other less-well-understood environmental mutagens
Dupuytren diathesis and genetic risk
Dolmans, Guido H; de Bock, Geertruida H; Werker, Paul M
2012-01-01
PURPOSE: Dupuytren disease (DD) is a benign fibrosing disorder of the hand and fingers. Recently, we identified 9 single nucleotide polymorphisms (SNPs) associated with DD in a genome-wide association study. These SNPs can be used to calculate a genetic risk score for DD. The aim of this study was
VTE Risk assessment - a prognostic Model: BATER Cohort Study of young women.
Heinemann, Lothar Aj; Dominh, Thai; Assmann, Anita; Schramm, Wolfgang; Schürmann, Rolf; Hilpert, Jan; Spannagl, Michael
2005-04-18
BACKGROUND: Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE). There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. MATERIALS AND METHODS: A 10-year observation period of the Bavarian Thromboembolic Risk (BATER) study, a cohort study of 4337 women (18-55 years), was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993). The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. RESULTS: Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs). A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI) and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation). Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%), moderate risk (21.1%), high risk (6.0%), very high risk of future VTE (0.9%). In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 104 WYs for no, moderate, high, and very high risk, respectively. CONCLUSION: Our prognostic tool - containing clinical information (and if available also genetic data) - seems to be
Krakow, Melinda; Ratcliff, Chelsea L; Hesse, Bradford W; Greenberg-Worisek, Alexandra J
2018-05-31
Public understanding of the role of genetics in disease risk is key to appropriate disease prevention and detection. This study assessed the current extent of awareness and use of genetic testing in the US population. Additionally, the study identified characteristics of subgroups more likely to be at risk for low genetic literacy. The study used data from the National Cancer Institute's 2017 Health Information National Trends Survey, including measures of genetic testing awareness, genetic testing applications and genetic testing usage. Multivariable logistic regression models estimated associations between sociodemographics, genetic testing awareness, and genetic testing use. Fifty-seven percent of respondents were aware of genetic tests. Testing awareness differed by age, household income, and race/ethnicity. Most participants had heard of using tests to determine personal disease risk (82.58%) or inherited disease risk in children (81.41%), but less were familiar with determining treatment (38.29%) or drug efficacy (40.76%). Among those with genetic testing awareness, actual testing uptake was low. A large portion of the general public lacks genetic testing awareness and may benefit from educational campaigns. As precision medicine expands, increasing public awareness about genetic testing applications for disease prevention and treatment will be important to support population health. This is a work of the US Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.
van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Bröcker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; van Gool, A. R.; Klijn, J. G. M.; Tibben, A.
2006-01-01
This study explores the effect of age at the time of parental cancer diagnosis or death on psychological distress and cancer risk perception in individuals undergoing genetic testing for a specific cancer susceptibility. Cancer-related distress, worry and risk perception were assessed in 271
Lee, Whiwon; Veach, Patricia McCarthy; MacFarlane, Ian M; LeRoy, Bonnie S
2015-04-01
Compassion fatigue is a state of detachment and isolation experienced when healthcare providers repeatedly engage with patients in distress. Compassion fatigue can hinder empathy and cause extreme tension. Prior research suggests 73.8 % of genetic counselors are at moderate to high risk for compassion fatigue and approximately 1 in 4 have considered leaving the field as a result Injeyan et al. (Journal of Genetic Counseling, 20, 526-540, 2011). Empirical data to establish a reliable profile of genetic counselors at risk for compassion fatigue are limited. Thus the purpose of this study was to establish a profile by assessing relationships between state and trait anxiety, burnout, compassion satisfaction, selected demographics and compassion fatigue risk in practicing genetic counselors. Practicing genetic counselors (n = 402) completed an anonymous, online survey containing demographic questions, the State-Trait Anxiety Inventory, and the Professional Quality of Life scale. Multiple regression analysis yielded four significant predictors which increase compassion fatigue risk (accounting for 48 % of the variance): higher levels of trait anxiety, burnout, and compassion satisfaction, and ethnicity other than Caucasian. Additional findings, study limitations, practice implications, and research recommendations are provided.
Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children
DEFF Research Database (Denmark)
Lundbo, Lene F; Harboe, Zitta Barrella; Clausen, Louise N
2016-01-01
NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). METHODS: Cases with IPD and IMD and controls were identified......BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-κB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes.......86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. CONCLUSIONS: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis....
Environmental risk assessment in GMO analysis.
Pirondini, Andrea; Marmiroli, Nelson
2010-01-01
Genetically modified or engineered organisms (GMOs, GEOs) are utilised in agriculture, expressing traits of interest, such as insect or herbicide resistance. Soybean, maize, cotton and oilseed rape are the GM crops with the largest acreage in the world. The distribution of GM acreage in the different countries is related with the different positions concerning labelling of GMO products: based on the principle of substantial equivalence, or rather based on the precautionary principle. The paper provides an overview on how the risks associated with release of GMO in the environments can be analysed and predicted, in view of a possible coexistence of GM and non-GM organisms in agriculture.Risk assessment procedures, both qualitative and quantitative, are compared in the context of application to GMOs considering also legislation requirements (Directive 2001/18/EC). Criteria and measurable properties to assess harm for human health and environmental safety are listed, and the possible consequences are evaluated in terms of significance.Finally, a mapping of the possible risks deriving from GMO release is reported, focusing on gene transfer to related species, horizontal gene transfer, direct and indirect effects on non target organisms, development of resistance in target organisms, and effects on biodiversity.
Graef, F.; Römbke, J.; Binimelis, R.; Myhr, A.I.; Hilbeck, A.; Breckling, B.; Dalgaard, T.; Stachow, U.; Catacora-Vargas, G.; Bohn, T.; Quist, D.; Darvas, B.; Dudel, G.; Oehen, B.; Meyer, H.; Henle, K.; Wynne, B.; Metzger, M.J.; Knäbe, S.; Settele, J.; Székács, A.; Wurbs, A.; Bernard, J.P.; Murphy-Bokern, D.; Buiatti, M.; Giovannetti, M.; Debeljak, M.; Andersen, E.; Paetz, A.; Dzeroski, S.; Tappeser, B.; van Gestel, C.A.M.; Wosniok, W.; Séralini, G.-E.; Aslaksen, I.; Pesch, R.; Maly, S.; Werner, A.
2012-01-01
The assessment of the impacts of growing genetically modified (GM) crops remains a major political and scientific challenge in Europe. Concerns have been raised by the evidence of adverse and unexpected environmental effects and differing opinions on the outcomes of environmental risk assessments
International Nuclear Information System (INIS)
Kinchin, G.H.
1983-01-01
After defining risk and introducing the concept of individual and societal risk, the author considers each of these, restricting considerations to risk of death. Some probabilities of death arising from various causes are quoted, and attention drawn to the care necessary in making comparisons between sets of data and to the distinction between voluntary and involuntary categories and between early and delayed deaths. The presentation of information on societal risk is discussed and examples given. The history of quantified risk assessment is outlined, particularly related to the nuclear industry, the process of assessing risk discussed: identification of hazard causes, the development of accident chains and the use of event trees, the evaluation of probability through the collection of data and their use with fault trees, and the assessment of consequences of hazards in terms of fatalities. Reference is made to the human element and common-made failures, and to studies supporting the development of reliability assessment techniques. Acceptance criteria are discussed for individual and societal risk in the nuclear field, and it is shown that proposed criteria lead to risks conservative by comparison with risks from day-to-day accidents and other potentially hazardous industries. (U.K.)
Prassinos, Peter G.; Lyver, John W., IV; Bui, Chinh T.
2011-01-01
Risk assessment is used in many industries to identify and manage risks. Initially developed for use on aeronautical and nuclear systems, risk assessment has been applied to transportation, chemical, computer, financial, and security systems among others. It is used to gain an understanding of the weaknesses or vulnerabilities in a system so modification can be made to increase operability, efficiency, and safety and to reduce failure and down-time. Risk assessment results are primary inputs to risk-informed decision making; where risk information including uncertainty is used along with other pertinent information to assist management in the decision-making process. Therefore, to be useful, a risk assessment must be directed at specific objectives. As the world embraces the globalization of trade and manufacturing, understanding the associated risk become important to decision making. Applying risk assessment techniques to a global system of development, manufacturing, and transportation can provide insight into how the system can fail, the likelihood of system failure and the consequences of system failure. The risk assessment can identify those elements that contribute most to risk and identify measures to prevent and mitigate failures, disruptions, and damaging outcomes. In addition, risk associated with public and environment impact can be identified. The risk insights gained can be applied to making decisions concerning suitable development and manufacturing locations, supply chains, and transportation strategies. While risk assessment has been mostly applied to mechanical and electrical systems, the concepts and techniques can be applied across other systems and activities. This paper provides a basic overview of the development of a risk assessment.
Health risks (early, delayed and genetic) from the present radiation level
International Nuclear Information System (INIS)
Stranden, E.
1981-01-01
A general survey is given of the risks of early, delayed and genetic injuries from present radiation environment. Brief data is presented on some industrial and medical accidents. It is stated that in Norway there are 5-10 incidents per year in industrial radiography, none of which have led to radiation syndrome. Delayed radiation effects are discussed and figures quoted for risk due to mining, industrial and medical radiography and natural sources. Genetic effects are similarly discussed and genetically significant doses from similar sources are quoted. It is concluded that the health risk from the radiation environment is very small compared with other risks. (JIW)
Genetic determinants of financial risk taking.
Kuhnen, Camelia M; Chiao, Joan Y
2009-01-01
Individuals vary in their willingness to take financial risks. Here we show that variants of two genes that regulate dopamine and serotonin neurotransmission and have been previously linked to emotional behavior, anxiety and addiction (5-HTTLPR and DRD4) are significant determinants of risk taking in investment decisions. We find that the 5-HTTLPR s/s allele carriers take 28% less risk than those carrying the s/l or l/l alleles of the gene. DRD4 7-repeat allele carriers take 25% more risk than individuals without the 7-repeat allele. These findings contribute to the emerging literature on the genetic determinants of economic behavior.
Introduction to risk assessment
International Nuclear Information System (INIS)
Raina, V.M.
2002-01-01
This paper gives an introduction to risk assessment. It discusses the basic concepts of risk assessment, nuclear risk assessment process and products, the role of risk assessment products in nuclear safety assurance, the relationship between risk assessment and other safety analysis and risk assessment and safe operating envelope
Cumulative Risk Assessment (CRA): transforming the way we assess health risks.
Williams, Pamela R D; Dotson, G Scott; Maier, Andrew
2012-10-16
Human health risk assessments continue to evolve and now focus on the need for cumulative risk assessment (CRA). CRA involves assessing the combined risk from coexposure to multiple chemical and nonchemical stressors for varying health effects. CRAs are broader in scope than traditional chemical risk assessments because they allow for a more comprehensive evaluation of the interaction between different stressors and their combined impact on human health. Future directions of CRA include greater emphasis on local-level community-based assessments; integrating environmental, occupational, community, and individual risk factors; and identifying and implementing common frameworks and risk metrics for incorporating multiple stressors.
Quantifying introgression risk with realistic population genetics
Ghosh, Atiyo; Meirmans, Patrick G.; Haccou, Patsy
2012-01-01
Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified crop regulation. Most theoretical introgression studies aimed at such quantification disregard one or more of the most important factors concerning introgression: realistic genetical mechanisms, rep...
Establishing a family risk assessment clinic for breast cancer.
LENUS (Irish Health Repository)
Mulsow, Jurgen
2012-02-01
Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1\\/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.
An animal model of differential genetic risk for methamphetamine intake
Directory of Open Access Journals (Sweden)
Tamara ePhillips
2015-09-01
Full Text Available The question of whether genetic factors contribute to risk for methamphetamine (MA use and dependence has not been intensively investigated. Compared to human populations, genetic animal models offer the advantages of control over genetic family history and drug exposure. Using selective breeding, we created lines of mice that differ in genetic risk for voluntary MA intake and identified the chromosomal addresses of contributory genes. A quantitative trait locus was identified on chromosome 10 that accounts for more than 50% of the genetic variance in MA intake in the selected mouse lines. In addition, behavioral and physiological screening identified differences corresponding with risk for MA intake that have generated hypotheses that are testable in humans. Heightened sensitivity to aversive and certain physiological effects of MA, such as MA-induced reduction in body temperature, are hallmarks of mice bred for low MA intake. Furthermore, unlike MA-avoiding mice, MA-preferring mice are sensitive to rewarding and reinforcing MA effects, and to MA-induced increases in brain extracellular dopamine levels. Gene expression analyses implicate the importance of a network enriched in transcription factor genes, some of which regulate the mu opioid receptor gene, Oprm1, in risk for MA use. Neuroimmune factors appear to play a role in differential response to MA between the mice bred for high and low intake. In addition, chromosome 10 candidate gene studies provide strong support for a trace amine associated receptor 1 gene, Taar1, polymorphism in risk for MA intake. MA is a trace amine-associated receptor 1 (TAAR1 agonist, and a non-functional Taar1 allele segregates with high MA consumption. Thus, reduced TAAR1 function has the potential to increase risk for MA use. Overall, existing findings support the MA drinking lines as a powerful model for identifying genetic factors involved in determining risk for harmful MA use. Future directions include the
A genetic risk score combining ten psoriasis risk loci improves disease prediction.
Directory of Open Access Journals (Sweden)
Haoyan Chen
2011-04-01
Full Text Available Psoriasis is a chronic, immune-mediated skin disease affecting 2-3% of Caucasians. Recent genetic association studies have identified multiple psoriasis risk loci; however, most of these loci contribute only modestly to disease risk. In this study, we investigated whether a genetic risk score (GRS combining multiple loci could improve psoriasis prediction. Two approaches were used: a simple risk alleles count (cGRS and a weighted (wGRS approach. Ten psoriasis risk SNPs were genotyped in 2815 case-control samples and 858 family samples. We found that the total number of risk alleles in the cases was significantly higher than in controls, mean 13.16 (SD 1.7 versus 12.09 (SD 1.8, p = 4.577×10(-40. The wGRS captured considerably more risk than any SNP considered alone, with a psoriasis OR for high-low wGRS quartiles of 10.55 (95% CI 7.63-14.57, p = 2.010×10(-65. To compare the discriminatory ability of the GRS models, receiver operating characteristic curves were used to calculate the area under the curve (AUC. The AUC for wGRS was significantly greater than for cGRS (72.0% versus 66.5%, p = 2.13×10(-8. Additionally, the AUC for HLA-C alone (rs10484554 was equivalent to the AUC for all nine other risk loci combined (66.2% versus 63.8%, p = 0.18, highlighting the dominance of HLA-C as a risk locus. Logistic regression revealed that the wGRS was significantly associated with two subphenotypes of psoriasis, age of onset (p = 4.91×10(-6 and family history (p = 0.020. Using a liability threshold model, we estimated that the 10 risk loci account for only 11.6% of the genetic variance in psoriasis. In summary, we found that a GRS combining 10 psoriasis risk loci captured significantly more risk than any individual SNP and was associated with early onset of disease and a positive family history. Notably, only a small fraction of psoriasis heritability is captured by the common risk variants identified to date.
A systematic approach to assessing the clinical significance of genetic variants.
Duzkale, H; Shen, J; McLaughlin, H; Alfares, A; Kelly, M A; Pugh, T J; Funke, B H; Rehm, H L; Lebo, M S
2013-11-01
Molecular genetic testing informs diagnosis, prognosis, and risk assessment for patients and their family members. Recent advances in low-cost, high-throughput DNA sequencing and computing technologies have enabled the rapid expansion of genetic test content, resulting in dramatically increased numbers of DNA variants identified per test. To address this challenge, our laboratory has developed a systematic approach to thorough and efficient assessments of variants for pathogenicity determination. We first search for existing data in publications and databases including internal, collaborative and public resources. We then perform full evidence-based assessments through statistical analyses of observations in the general population and disease cohorts, evaluation of experimental data from in vivo or in vitro studies, and computational predictions of potential impacts of each variant. Finally, we weigh all evidence to reach an overall conclusion on the potential for each variant to be disease causing. In this report, we highlight the principles of variant assessment, address the caveats and pitfalls, and provide examples to illustrate the process. By sharing our experience and providing a framework for variant assessment, including access to a freely available customizable tool, we hope to help move towards standardized and consistent approaches to variant assessment. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Goddard, K A B; Robitaille, J; Dowling, N F; Parrado, A R; Fishman, J; Bradley, L A; Moore, C A; Khoury, M J
2009-01-01
Recent years have seen increased concern about direct-to-consumer (DTC) genetic testing (i.e., the sale and use of genetic tests without involving a health care provider). Numerous professional organizations have developed policies in this area. However, little systematic evidence exists to inform public policy about these tests. We conducted a systematic search to identify genetic tests that are sold DTC without involving a health care provider. We evaluated the practices of companies offering DTC genetic tests for risk of thrombosis using criteria from multiple sources and a minimal set of key practices. We identified 84 instances of currently available health-related DTC genetic tests sold on 27 Web sites; the most common were for pharmacogenomics (12), risk of thrombosis (10), and nutrigenomics (10). For the DTC genetic tests for risk of thrombosis, we found low adherence to recommendations. Online information was frequently incomplete and had low agreement with professional recommendations. Our findings document the rapid growth in the availability of health-related DTC genetic tests and highlight the need to improve the delivery of DTC genetic tests. A major implication of this study is the need for the scientific and medical community to develop consistent recommendations to increase their impact. Copyright 2008 S. Karger AG, Basel.
VTE Risk assessment – a prognostic Model: BATER Cohort Study of young women
Directory of Open Access Journals (Sweden)
Schürmann Rolf
2005-04-01
Full Text Available Abstract Background Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE. There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. Materials and methods A 10-year observation period of the Bavarian Thromboembolic Risk (BATER study, a cohort study of 4337 women (18–55 years, was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993. The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. Results Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs. A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation. Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%, moderate risk (21.1%, high risk (6.0%, very high risk of future VTE (0.9%. In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 104 WYs for no, moderate, high, and very high risk, respectively. Conclusion Our prognostic tool – containing clinical information (and if available also genetic data
Protection goals in environmental risk assessment: a practical approach.
Garcia-Alonso, Monica; Raybould, Alan
2014-12-01
Policy protection goals are set up in most countries to minimise harm to the environment, humans and animals caused by human activities. Decisions on whether to approve new agricultural products, like pesticides or genetically modified (GM) crops, take into account these policy protection goals. To support decision-making, applications for approval of commercial uses of GM crops usually comprise an environmental risk assessment (ERA). These risk assessments are analytical tools, based on science, that follow a conceptual model that includes a problem formulation step where policy protection goals are considered. However, in most countries, risk assessors face major problems in that policy protection goals set in the legislation are stated in very broad terms and are too ambiguous to be directly applicable in ERAs. This means that risk assessors often have to interpret policy protection goals without clear guidance on what effects would be considered harmful. In this paper we propose a practical approach that may help risk assessors to translate policy protection goals into unambiguous (i.e., operational) protection goals and to establish relevant assessment endpoints and risk hypotheses that can be used in ERAs. Examples are provided to show how this approach can be applied to two areas of environmental concern relevant to the ERAs of GM crops.
Genetic and epigenetic risks of assisted reproduction.
Jiang, Ziru; Wang, Yinyu; Lin, Jing; Xu, Jingjing; Ding, Guolian; Huang, Hefeng
2017-10-01
Assisted reproductive technology (ART) is used primarily for infertility treatments to achieve pregnancy and involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and cryopreservation. Moreover, preimplantation genetic diagnosis (PGD) of ART is used in couples for genetic reasons. In ART treatments, gametes and zygotes are exposed to a series of non-physiological processes and culture media. Although the majority of children born with this treatment are healthy, some concerns remain regarding the safety of this technology. Animal studies and follow-up studies of ART-borne children suggested that ART was associated with an increased incidence of genetic, physical, or developmental abnormalities, although there are also observations that contradict these findings. As IVF, ICSI, frozen-thawed embryo transfer, and PGD manipulate gametes and embryo at a time that is important for reprogramming, they may affect epigenetic stability, leading to gamete/embryo origins of adult diseases. In fact, ART offspring have been reported to have an increased risk of gamete/embryo origins of adult diseases, such as early-onset diabetes, cardiovascular disease, and so on. In this review, we will discuss evidence related to genetic, especially epigenetic, risks of assisted reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.
Cedillos-Whynott, Elizabeth M.; Wolfe, Christopher R.; Widmer, Colin L.; Brust-Renck, Priscila G.; Weil, Audrey; Reyna, Valerie F.
2017-01-01
BRCA Gist is an Intelligent Tutoring System that helps women understand issues related to genetic testing and breast cancer risk. In two laboratory experiments and a field experiment with community and web-based samples, an avatar asked 120 participants to produce arguments for and against genetic testing for breast cancer risk. Two raters assessed the number of argumentation elements (claim, reason, backing, etc.) found in response to prompts soliciting arguments for and against genetic testing for breast cancer risk (IRR=.85). When asked to argue for genetic testing, 53.3 % failed to meet the minimum operational definition of making an argument, a claim supported by one or more reasons. When asked to argue against genetic testing, 59.3 % failed to do so. Of those who failed to generate arguments most simply listed disconnected reasons. However, participants who provided arguments against testing (40.7 %) performed significantly higher on a posttest of declarative knowledge. In each study we found positive correlations between the quality of arguments against genetic testing (i.e., number of argumentation elements) and genetic risk categorization scores. Although most interactions did not contain two or more argument elements, when more elements of arguments were included in the argument against genetic testing interaction, participants had greater learning outcomes. Apparently, many participants lack skills in making coherent arguments. These results suggest an association between argumentation ability (knowing how to make complex arguments) and subsequent learning. Better education in developing arguments may be necessary for people to learn from generating arguments within Intelligent Tutoring Systems and other settings. PMID:26511370
Heinemann, Jack A; Agapito-Tenfen, Sarah Zanon; Carman, Judy A
2013-05-01
Changing the nature, kind and quantity of particular regulatory-RNA molecules through genetic engineering can create biosafety risks. While some genetically modified organisms (GMOs) are intended to produce new regulatory-RNA molecules, these may also arise in other GMOs not intended to express them. To characterise, assess and then mitigate the potential adverse effects arising from changes to RNA requires changing current approaches to food or environmental risk assessments of GMOs. We document risk assessment advice offered to government regulators in Australia, New Zealand and Brazil during official risk evaluations of GM plants for use as human food or for release into the environment (whether for field trials or commercial release), how the regulator considered those risks, and what that experience teaches us about the GMO risk assessment framework. We also suggest improvements to the process. Copyright © 2013 Elsevier Ltd. All rights reserved.
Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.
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.
Directory of Open Access Journals (Sweden)
Cho AH
2012-01-01
Full Text Available Alex H Cho1, Xiaolei Jiang2, Devin M Mann3, Kensaku Kawamoto4, Timothy J Robinson5, Nancy Wang6, Jeanette J McCarthy2, Mark Woodward7, Geoffrey S Ginsburg1,21Center for Personalized Medicine and Department of Medicine, Duke University, Durham, NC, 2Institute for Genome Sciences and Policy, Duke University, Durham, NC, 3Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, 4Department of Biomedical Informatics, University of Utah, Salt Lake City, UT, 5Medical College of Virginia, Richmond, VA, 6School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA; 7George Institute for Global Health and University of Sydney, AustraliaBackground: Comparative effectiveness research and research in genomic medicine are not orthogonal pursuits. Both require a robust evidence base, and each stands to benefit from applying the methods of the other. There is an exponentially growing literature reporting associations between single nucleotide polymorphisms (SNPs and increased risk for diseases such as type 2 diabetes. Literature-based meta-analysis is an important method of assessing the validity of published gene-disease associations, but a traditional emphasis on exhaustiveness makes it difficult to study multiple polymorphisms efficiently. Here we describe a novel two-step search method for broadly yet systematically reviewing the literature to identify the "most-studied" gene-disease associations, thereby selecting those with a high possibility of replication on which to conduct abbreviated, simultaneous meta-analyses. This method was then applied to identify and evaluate the validity of SNPs reported to be associated with increased type 2 diabetes risk, to demonstrate proof of principle.Methods: A two-step MEDLINE search (1950 to present was conducted in September 2007 for published genetic association data related to SNPs associated with risk of type 2 diabetes. The
Genetic factors affecting dental caries risk.
Opal, S; Garg, S; Jain, J; Walia, I
2015-03-01
This article reviews the literature on genetic aspects of dental caries and provides a framework for the rapidly changing disease model of caries. The scope is genetic aspects of various dental factors affecting dental caries. The PubMed database was searched for articles with keywords 'caries', 'genetics', 'taste', 'diet' and 'twins'. This was followed by extensive handsearching using reference lists from relevant articles. The post-genomic era will present many opportunities for improvement in oral health care but will also present a multitude of challenges. We can conclude from the literature that genes have a role to play in dental caries; however, both environmental and genetic factors have been implicated in the aetiology of caries. Additional studies will have to be conducted to replicate the findings in a different population. Identification of genetic risk factors will help screen and identify susceptible patients to better understand the contribution of genes in caries aetiopathogenesis. Information derived from these diverse studies will provide new tools to target individuals and/or populations for a more efficient and effective implementation of newer preventive measures and diagnostic and novel therapeutic approaches in the management of this disease. © 2015 Australian Dental Association.
McKim, Vicky L
2017-06-01
In the world of risk management, which encompasses the business continuity disciplines, many types of risk require evaluation. Financial risk is most often the primary focus, followed by product and market risks. Another critical area, which typically lacks a thorough review or may be overlooked, is operational risk. This category encompasses many risk exposure types including those around building structures and systems, environmental issues, nature, neighbours, clients, regulatory compliance, network, data security and so on. At times, insurance carriers will assess internal hazards, but seldom do these assessments include more than a cursory look at other types of operational risk. In heavily regulated environments, risk assessments are required but may not always include thorough assessments of operational exposures. Vulnerabilities may linger or go unnoticed, only to become the catalyst for a business disruption at a later time, some of which are so severe that business recovery becomes nearly impossible. Businesses may suffer loss of clients as the result of a prolonged disruption of services. Comprehensive operational risk assessments can assist in identifying such vulnerabilities, exposures and threats so that the risk can be minimised or removed. This paper lays out how an assessment of this type can be successfully conducted.
van Capelle, Christine; Schrader, Stefan; Arpaia, Salvatore
2016-04-01
By means of a literature survey, earthworm species of significant relevance for soil functions in different biogeographical regions of Europe (Atlantic, Boreal, Mediterranean) were identified. These focal earthworm species, defined here according to the EFSA Guidance Document on the environmental risk assessment (ERA) of genetically modified plants, are typical for arable soils under crop rotations with maize and/or potatoes within the three regions represented by Ireland, Sweden and Spain, respectively. Focal earthworm species were selected following a matrix of four steps: Identification of functional groups, categorization of non-target species, ranking species on ecological criteria, and final selection of focal species. They are recommended as appropriate non-target organisms to assess environmental risks of genetically modified (GM) crops; in this case maize and potatoes. In total, 44 literature sources on earthworms in arable cropping systems including maize or potato from Ireland, Sweden and Spain were collected, which present information on species diversity, individual density and specific relevance for soil functions. By means of condensed literature data, those species were identified which (i) play an important functional role in respective soil systems, (ii) are well adapted to the biogeographical regions, (iii) are expected to occur in high abundances under cultivation of maize or potato and (iv) fulfill the requirements for an ERA test system based on life-history traits. First, primary and secondary decomposers were identified as functional groups being exposed to the GM crops. In a second step, anecic and endogeic species were categorized as potential species. In step three, eight anecic and endogeic earthworm species belonging to the family Lumbricidae were ranked as relevant species: Aporrectodea caliginosa, Aporrectodea rosea, Aporrectodea longa, Allolobophora chlorotica, Lumbricus terrestris, Lumbricus friendi, Octodrilus complanatus and
Risks and benefits of genetically modified foods
African Journals Online (AJOL)
Jane
2011-09-30
Sep 30, 2011 ... education on the subject to the public. Modern ... published were on the progress of GMF technology followed by attitude studies (such as perceptions ..... Genetically Modified Corn: Environmental Benefits and. Risks.
Molecular mechanisms of the genetic risk factors in pathogenesis of Alzheimer disease.
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.
MacGregor, James T; Frötschl, Roland; White, Paul A; Crump, Kenny S; Eastmond, David A; Fukushima, Shoji; Guérard, Melanie; Hayashi, Makoto; Soeteman-Hernández, Lya G; Johnson, George E; Kasamatsu, Toshio; Levy, Dan D; Morita, Takeshi; Müller, Lutz; Schoeny, Rita; Schuler, Maik J; Thybaud, Véronique
2015-05-01
This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose-response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clastogenic damage for agents thought to act via a genotoxic mechanism, but that the correlation is limited due to an inadequate number of cases in which mutation and cancer can be compared at a sufficient number of doses in the same target tissues of the same species and strain exposed under directly comparable routes and experimental protocols. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.
Assessment of the genetic diversity and pattern of relationship of ...
African Journals Online (AJOL)
An understanding of the extent, distribution and patterns of genetic variation is useful for estimation of any possible loss of genetic diversity and assessment of genetic variability and its potential use in breeding programs, including establishment of heterotic groups. This study assessed patterns of genetic diversity and ...
Abnormal temporal lobe white matter as a biomarker for genetic risk of bipolar disorder.
Mahon, Katie; Burdick, Katherine E; Ikuta, Toshikazu; Braga, Raphael J; Gruner, Patricia; Malhotra, Anil K; Szeszko, Philip R
2013-01-15
Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD (n=26), unaffected siblings of patients with BD (n=15), and healthy volunteers (n=27) to identify WM biomarkers of genetic risk. The FA differed significantly (punaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Night Shift Work, Genetic Risk, and Type 2 Diabetes in the UK Biobank.
Vetter, Céline; Dashti, Hassan S; Lane, Jacqueline M; Anderson, Simon G; Schernhammer, Eva S; Rutter, Martin K; Saxena, Richa; Scheer, Frank A J L
2018-04-01
To examine the effects of past and current night shift work and genetic type 2 diabetes vulnerability on type 2 diabetes odds. In the UK Biobank, we examined associations of current ( N = 272,214) and lifetime ( N = 70,480) night shift work exposure with type 2 diabetes risk (6,770 and 1,191 prevalent cases, respectively). For 180,704 and 44,141 unrelated participants of European ancestry (4,002 and 726 cases, respectively) with genetic data, we assessed whether shift work exposure modified the relationship between a genetic risk score (comprising 110 single-nucleotide polymorphisms) for type 2 diabetes and prevalent diabetes. Compared with day workers, all current night shift workers were at higher multivariable-adjusted odds for type 2 diabetes (none or rare night shifts: odds ratio [OR] 1.15 [95% CI 1.05-1.26]; some nights: OR 1.18 [95% CI 1.05-1.32]; and usual nights: OR 1.44 [95% CI 1.19-1.73]), except current permanent night shift workers (OR 1.09 [95% CI 0.93-1.27]). Considering a person's lifetime work schedule and compared with never shift workers, working more night shifts per month was associated with higher type 2 diabetes odds (8/month: OR 1.36 [95% CI 1.14-1.62]; P trend = 0.001). The association between genetic type 2 diabetes predisposition and type 2 diabetes odds was not modified by shift work exposure. Our findings show that night shift work, especially rotating shift work including night shifts, is associated with higher type 2 diabetes odds and that the number of night shifts worked per month appears most relevant for type 2 diabetes odds. Also, shift work exposure does not modify genetic risk for type 2 diabetes, a novel finding that warrants replication. © 2018 by the American Diabetes Association.
Safety assessment of foods derived from genetically modified crops
Kleter, G.A.; Kuiper, H.A.
2003-01-01
The pre-market safety assessment of foods derived from genetically modified crops is carried out according to the consensus approach of "substantial equivalence", in other words: the comparative safety assessment. Currently, the safety assessment of genetically modified foods is harmonized at the
Tang, Jinsong; Fan, Yu; Li, Hong; Xiang, Qun; Zhang, Deng-Feng; Li, Zongchang; He, Ying; Liao, Yanhui; Wang, Ya; He, Fan; Zhang, Fengyu; Shugart, Yin Yao; Liu, Chunyu; Tang, Yanqing; Chan, Raymond C K; Wang, Chuan-Yue; Yao, Yong-Gang; Chen, Xiaogang
2017-06-20
Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. All rights reserved.
The structure of genetic and environmental risk factors for fears and phobias.
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.
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Risk factors for Alzheimer's disease : a genetic-epidemiologic study
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 liability for schizophrenia predicts risk of immune disorders
Stringer, Sven; Kahn, René S.; de Witte, Lot D.; Ophoff, Roel A.; Derks, Eske M.
2014-01-01
Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between
Genetic liability for schizophrenia predicts risk of immune disorders
Stringer, Sven; Kahn, René S; de Witte, Lot D; Ophoff, Roel A; Derks, Eske M
2014-01-01
BACKGROUND: Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap
Mazzucchelli, Gabriel; Holzhauser, Thomas; Cirkovic Velickovic, Tanja; Diaz-Perales, Araceli; Molina, Elena; Roncada, Paola; Rodrigues, Pedro; Verhoeckx, Kitty; Hoffmann-Sommergruber, Karin
2018-01-01
Food allergies are recognized as a global health concern. In order to protect allergic consumers from severe symptoms, allergenic risk assessment for well-known foods and foods containing genetically modified ingredients is installed. However, population is steadily growing and there is a rising need to provide adequate protein-based foods, including novel sources, not yet used for human consumption. In this context safety issues such as a potential increased allergenic risk need to be assessed before marketing novel food sources. Therefore, the established allergenic risk assessment for genetically modified organisms needs to be re-evaluated for its applicability for risk assessment of novel food proteins. Two different scenarios of allergic sensitization have to be assessed. The first scenario is the presence of already known allergenic structures in novel foods. For this, a comparative assessment can be performed and the range of cross-reactivity can be explored, while in the second scenario allergic reactions are observed toward so far novel allergenic structures and no reference material is available. This review summarizes the current analytical methods for allergenic risk assessment, highlighting the strengths and limitations of each method and discussing the gaps in this assessment that need to be addressed in the near future. © 2017 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Pasquale, Louis R; Aschard, Hugues; Kang, Jae H; Bailey, Jessica N Cooke; Lindström, Sara; Chasman, Daniel I; Christen, William G; Allingham, R Rand; Ashley-Koch, Allison; Lee, Richard K; Moroi, Sayoko E; Brilliant, Murray H; Wollstein, Gadi; Schuman, Joel S; Fingert, John; Budenz, Donald L; Realini, Tony; Gaasterland, Terry; Gaasterland, Douglas; Scott, William K; Singh, Kuldev; Sit, Arthur J; Igo, Robert P; Song, Yeunjoo E; Hark, Lisa; Ritch, Robert; Rhee, Douglas J; Gulati, Vikas; Havens, Shane; Vollrath, Douglas; Zack, Donald J; Medeiros, Felipe; Weinreb, Robert N; Pericak-Vance, Margaret A; Liu, Yutao; Kraft, Peter; Richards, Julia E; Rosner, Bernard A; Hauser, Michael A; Haines, Jonathan L; Wiggs, Janey L
2017-02-01
Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. Using data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. The genetic risk score was associated with self-reported ANM (P = 2.2 × 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.
Jonas, Susanna; Wild, Claudia; Schamberger, Chantal
2003-02-01
The aim of this health technology assessment was to analyse the current scientific and genetic counselling on predictive genetic testing for hereditary breast and colorectal cancer. Predictive genetic testing will be available for several common diseases in the future and questions related to financial issues and quality standards will be raised. This report is based on a systematic/nonsystematic literature search in several databases (e.g. EmBase, Medline, Cochrane Library) and on a specific health technology assessment report (CCOHTA) and review (American Gastroenterological Ass.), respectively. Laboratory test methods, early detection methods and the benefit from prophylactic interventions were analysed and social consequences interpreted. Breast and colorectal cancer are counted among the most frequently cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gene is responsible for the increased cancer risk. In these families, high tumour frequency, young age at diagnosis and multiple primary tumours are remarkable. GENETIC DIAGNOSIS: Sequence analysis is the gold standard. Denaturing high performance liquid chromatography is a quick alternative method. The identification of the responsible gene defect in an affected family member is important. If the test result is positive there is an uncertainty whether the disease will develop or not, when and in which degree, which is founded in the geno-/phenotype correlation. The individual risk estimation is based upon empirical evidence. The test results affect the whole family. Currently, primary prevention is possible for familial adenomatous polyposis (celecoxib, prophylactic colectomy) and for hereditary mamma carcinoma (prophylactic mastectomy). The so-called preventive medical check-ups are early detection examinations. The evidence about early detection methods for colorectal cancer is better than for breast cancer. Prophylactic
Model of personalised risk assessment of phytoestrogen intake based on 11 SNP in ESR1 and ESR2 genes
Directory of Open Access Journals (Sweden)
Radoslav Zidek
2016-12-01
Full Text Available Phytoestrogens can induce biological responses in vertebrates by mimicking or modulating the action or production of endogenous hormones, and because of their structural similarity with estradiol they have the ability to cause estrogenic or anti-estrogenic effects. Risk assessment of phytoestrogens intake may therefore provide important information useful in the adjustment of nutrients composition, as one of nutrigenomics approaches. Proper risk assessment is an essential part of good nutrient composition. The current risk assessment procedures does use an additive effect of genes, but the accumulation of relevant factors do not count with the distribution of risk in the European population. A combination of approaches based on genetic score, along with the use of the data bases like 1000 genomes and dbSNP is a powerful tool for population risk modelling that would provide reasonable results without needs of as testing a representative number of individual genetic profiles.
An audit of clinical service examining the uptake of genetic testing by at-risk family members.
Forrest, Laura; Delatycki, Martin; Curnow, Lisette; Gen Couns, M; Skene, Loane; Aitken, Maryanne
2012-01-01
The aim of this study was to investigate the uptake of genetic testing by at-risk family members for four genetic conditions: chromosomal translocations, fragile X syndrome, Huntington disease, and spinal muscular atrophy. A clinical audit was undertaken using genetics files from Genetic Health Services Victoria. Data were extracted from the files regarding the number of at-risk family members and the proportion tested. Information was also collected about whether discussion of at-risk family members and family communication during the genetic consultation was recorded. The proportion of at-risk family members who had genetic testing ranged from 11% to 18%. First-degree family members were most frequently tested and the proportion of testing decreased by degree of relatedness to the proband. Smaller families were significantly more likely to have genetic testing for all conditions except Huntington disease. Female at-risk family members were significantly more likely to have testing for fragile X syndrome. The majority of at-risk family members do not have genetic testing. Family communication is likely to influence the uptake of genetic testing by at-risk family members and therefore it is important that families are supported while communicating to ensure that at-risk family members are able to make informed decisions about genetic testing.
Amara, Nabil; Blouin-Bougie, Jolyane; Jbilou, Jalila; Halilem, Norrin; Simard, Jacques; Landry, Réjean
2016-01-01
The aim of this paper is twofold: to analyze the genetic counseling process for breast cancer with a theoretical knowledge transfer lens and to compare generalists, medical specialists, and genetic counselors with regards to their genetic counseling practices. This paper presents the genetic counseling process occurring within a chain of value-adding activities of four main stages describing health professionals' clinical practices: (1) evaluation, (2) investigation, (3) information, and (4) decision. It also presents the results of a cross-sectional study based on a Canadian medical doctors and genetic counselors survey (n = 176) realized between July 2012 and March 2013. The statistical exercise included descriptive statistics, one-way ANOVA and post-hoc tests. The results indicate that even though all types of health professionals are involved in the entire process of genetic counseling for breast cancer, genetic counselors are more involved in the evaluation of breast cancer risk, while medical doctors are more active in the decision toward breast cancer risk management strategies. The results secondly demonstrate the relevance and the key role of genetic counselors in the care provided to women at-risk of familial breast cancer. This paper presents an integrative framework to understand the current process of genetic counseling for breast cancer in Canada, and to shed light on how and where health professionals contribute to the process. It also offers a starting point for assessing clinical practices in genetic counseling in order to establish more clearly where and to what extent efforts should be undertaken to implement future genetic services.
[About twins: Epidemiological, genetic, and obstetrical aspects, specific risks, and outcome].
Tauzin, M; Felix, A; Michot, C; Dedieu, C; Aoust, L; Fortas, F; Guillier, C; Ngo, J; Wachter, P-Y; Petermann, L; Kermorvant-Duchemin, E
2017-12-01
The incidence of twin pregnancies has increased steadily for the last 40 years due to assisted reproductive technology and increased maternal childbearing age. Multiple pregnancies, especially monochorionic twin pregnancies, carry a high risk for the mother and the fetuses and require close follow-up. Twins are exposed to a higher risk of perinatal anoxia, in utero fetal demise, preterm birth, congenital malformations, fetal growth restriction, and vascular complications. Compared to singletons, twins are at higher risk of perinatal mortality and impaired neurodevelopmental outcome, justifying a thorough follow-up by pediatricians, including assessment and management of familial and psychosocial impact. This paper discusses the epidemiological, obstetrical, and genetic issues raised by twin pregnancies and reviews the data on the perinatal and neurological long-term outcomes of twins, as well as the psychosocial impact of multiple births on twins and their families. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Earnhardt, Joanne M; Thompson, Steven D; Faust, Lisa J
2009-05-01
The Bali mynah Species Survival Plan (SSP), an Association of Zoos and Aquariums program, strives to maintain the genetic and demographic health of its population, avoid unplanned changes in size, and minimize the risk of population extinction. The SSP population meets current demographic and genetic objectives with a population size of 209 birds at 61 institutions and 96% genetic diversity (GD) retained from the source population. However, participating institutions have expressed concerns regarding space allocation, target population size (TPS), breeding restrictions, inbreeding depression, and harvest in relation to future population availability and viability. Based on these factors, we assess five questions with a quantitative risk assessment, specifically a population viability analysis (PVA) using ZooRisk software. Using an individual-based stochastic model, we project potential population changes under different conditions (e.g. changes in TPS and genetic management) to identify the most effective management actions. Our projections indicate that under current management conditions, population decline and extinction are unlikely and that although GD will decline over 100 years the projected loss does not exceed levels acceptable to population managers (less than 90% GD retained). Model simulations indicate that the combination of two genetic management strategies (i.e. priority breeding based on mean kinship and inbreeding avoidance) benefits the retention of GD and reduces the accumulation of inbreeding. The current TPS (250) is greater than necessary to minimize the risk of extinction for the SSP population but any reduction in TPS must be accompanied by continued application of genetic management. If carefully planned, birds can be harvested for transfer to Bali for a reintroduction program without jeopardizing the SSP population.
Vinnem, Jan-Erik
2014-01-01
Offshore Risk Assessment was the first book to deal with quantified risk assessment (QRA) as applied specifically to offshore installations and operations. Risk assessment techniques have been used for more than three decades in the offshore oil and gas industry, and their use is set to expand increasingly as the industry moves into new areas and faces new challenges in older regions. This updated and expanded third edition has been informed by a major R&D program on offshore risk assessment in Norway and summarizes research from 2006 to the present day. Rooted with a thorough discussion of risk metrics and risk analysis methodology, subsequent chapters are devoted to analytical approaches to escalation, escape, evacuation and rescue analysis of safety and emergency systems. Separate chapters analyze the main hazards of offshore structures: fire, explosion, collision, and falling objects as well as structural and marine hazards. Risk mitigation and control are discussed, as well as an illustrat...
Risk assessment and radioactive waste management
International Nuclear Information System (INIS)
Cohen, J.J.
1979-01-01
Problems of radioactive waste management, both real and apparent, have provided a serious constraint in the development of nuclear power. Several studies have been conducted in an attempt to evaluate the actual (quantifiable) risks of radioactive waste management and place them in a reasonable perspective. These studies are reviewed and discussed. Generally, the studies indicate the risks to be of a level of seriousness which might normally be considered acceptable in current society. However, it is apparent that this acceptability has not been attained and public apprehension prevails. To understand the reasons for this apprehension requires an assessment of those factors of ''perceived'' risks which play a major role in determining public attitudes toward radioactive waste management programs and nuclear power, in general. Such factors might include the spector of legacies of harm to future generations, genetic effects, nuclear garbage dumps, proliferation of plutonium inventories, nuclear terrorism, etc. A major problem in development of acceptable waste management policies and programs requires not only the recognition of the importance of perceived risk factors but development of a methodology for their incorporation in planning and conduct of such activities. Some approaches to the development of this methodology are discussed
Cerivastatin, Genetic Variants, and the Risk of Rhabdomyolysis
Marciante, Kristin D.; Durda, Jon P.; Heckbert, Susan R.; Lumley, Thomas; Rice, Ken; McKnight, Barbara; Totah, Rheem A.; Tamraz, Bani; Kroetz, Deanna L.; Fukushima, Hisayo; Kaspera, Rüdiger; Bis, Joshua C.; Glazer, Nicole L.; Li, Guo; Austin, Thomas R.; Taylor, Kent D.; Rotter, Jerome I.; Jaquish, Cashell E.; Kwok, Pui-Yan; Tracy, Russell P.; Psaty, Bruce M.
2011-01-01
Objective The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response--rhabdomyolysis in a small proportion of users-- points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis. Methods The study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association (GWA) study to identify risk factors in other regions of the genome. 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n=374) and the Heart and Vascular Health Study (n=358). Validation relied on functional studies. Results Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (p = 0.002), but not variants in CYP2C8 (p = 0.073) or the UGTs (p = 0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (OR: 1.89, 95% CI: 1.40 to 2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (p rhabdomyolysis (OR: 0.48; 95% CI: 0.36 to 0.63). Conclusion We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin. PMID:21386754
Hann, Katie E J; Freeman, Madeleine; Fraser, Lindsay; Waller, Jo; Sanderson, Saskia C; Rahman, Belinda; Side, Lucy; Gessler, Sue; Lanceley, Anne
2017-05-25
Genetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups' awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups. A search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included. Forty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment. Interventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and
Modelling the genetic risk in age-related macular degeneration.
Directory of Open Access Journals (Sweden)
Felix Grassmann
Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.
Prefrontal gray matter volume mediates genetic risks for obesity.
Opel, N; Redlich, R; Kaehler, C; Grotegerd, D; Dohm, K; Heindel, W; Kugel, H; Thalamuthu, A; Koutsouleris, N; Arolt, V; Teuber, A; Wersching, H; Baune, B T; Berger, K; Dannlowski, U
2017-05-01
Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.
Diffusion-weighted MRI for detecting prostate tumour in men at increased genetic risk
International Nuclear Information System (INIS)
Souza, Nandita M. de; Morgan, Veronica A.; Bancroft, Elizabeth; Sohaib, S. Aslam; Giles, Sharon L.; Kote-Jarai, Zsofia; Castro, Elena; Hazell, Steven; Jafar, Maysam; Eeles, Rosalind
2014-01-01
•Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening.•MRI is specific for detecting prostate cancer in men with increased genetic risk.•Detection of prostate cancer in men at genetically low risk with MRI is limited. Endorectal T2W + DW-MRI is potentially useful for prostate cancer screening. MRI is specific for detecting prostate cancer in men with increased genetic risk. Detection of prostate cancer in men at genetically low risk with MRI is limited. Diffusion-weighted (DW)-MRI is invaluable in detecting prostate cancer. We determined its sensitivity and specificity and established interobserver agreement for detecting tumour in men with a family history of prostate cancer stratified by genetic risk. 51 men with a family history of prostate cancer underwent T2-W + DW-endorectal MRI at 3.0 T. Presence of tumour was noted at right and left apex, mid and basal prostate sextants by 2 independent observers, 1 experienced and the other inexperienced in endorectal MRI. Sensitivity and specificity against a 10-core sampling technique (lateral and medial cores at each level considered together) in men with >2× population risk based on 71 SNP analysis versus those with lower genetic risk scores was established. Interobserver agreement was determined at a subject level. Biopsies indicated cancer in 28 sextants in 13/51 men; 32 of 51 men had twice the population risk (>0.25) based on 71 SNP profiling. Sensitivity/specificity per-subject for patients was 90.0%/86.4% (high-risk) vs. 66.7%/100% (low-risk, observer 1) and 60.0%/86.3% (high-risk) vs. 33.3%/93.8% (low-risk, observer 2) with moderate overall inter-observer agreement (kappa = 0.42). Regional sensitivities/specificities for high-risk vs. low-risk for observer 1 apex 72.2%/100% [33.3%/100%], mid 100%/93.1% [100%/97.3%], base 16.7%/98.3% [0%/100%] and for observer 2 apex 36.4%/98.1% [0%/100%], mid 28.6%/96.5% [100%/100%], base 20%/100% [0%/97.3%] were poorer as they failed to detect
Concept of risk: risk assessment and nuclear safety
International Nuclear Information System (INIS)
Thompson, P.B.
1980-01-01
The dissertation is a critical examination of risk assessment and its role in public policy. Nuclear power safety safety issues are selected as the primary source of illustrations and examples. The dissertation examines how risk assessment studies develop a concept of risk which becomes decisive for policy choices. Risk-assessment techniques are interpreted as instruments which secure an evaluation of risk which, in turn, figures prominently in technical reports on nuclear power. The philosophical critique is mounted on two levels. First, an epistemological critique surveys distinctions between the technical concept of risk and more familiar senses of risk. The critique shows that utilization of risk assessment re-structures the concept of risk. The technical concept is contrasted to the function of risk within a decision-maker's conceptual agenda and hierarchy of values. Second, an ethical critique exposes the value commitments of risk assessment recommendations. Although some of these values might be defended for policy decisions, the technical character of risk assessment obfuscates normative issues. Risk assessment is shown to be a form of factual enquiry which, nonetheless, represents a commitment to a specific selection of ethical and social values. Risk assessment should not be interpreted as a primary guide to decision unless the specific values incorporated into its concept of risk are stated explicitly and justified philosophically. Such a statement would allow value questions which have been sublimated by the factual tone of the analytic techniques to be debated on clear, social and ethical grounds
Genetically Predicted Body Mass Index and Breast Cancer Risk
DEFF Research Database (Denmark)
Guo, Yan; Warren Andersen, Shaneda; Shu, Xiao-Ou
2016-01-01
BACKGROUND: Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or enviro...
Easy calculations of lod scores and genetic risks on small computers.
Lathrop, G M; Lalouel, J M
1984-01-01
A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed. An illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy. PMID:6585139
Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.
Directory of Open Access Journals (Sweden)
Katie M O'Brien
Full Text Available Gastrointestinal stromal tumors (GISTs are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs and 95% confidence intervals (CIs for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT. Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836 and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836. CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively. Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic
Venema, A.
2015-01-01
The ‘Risico- Inventarisatie- en Evaluatie-instrumenten’ is the name for the Dutch risk assessment (RA) tools. A RA tool can be used to perform a risk assessment including an evaluation of the identified risks. These tools were among the first online risk assessment tools developed in Europe. The
Quantifying introgression risk with realistic population genetics
Ghosh, A.; Meirmans, P.G.; Haccou, P.
2012-01-01
Introgression is the permanent incorporation of genes from the genome of one population into another. This can have severe consequences, such as extinction of endemic species, or the spread of transgenes. Quantification of the risk of introgression is an important component of genetically modified
Dietary risk assessment of v-ATPase A dsRNAs on monarch butterfly larvae
The goal of this study is to assess the risks of RNA interference (RNAi)-based genetically engineered crops on a non-target arthropod, monarch butterfly, Danaus plexippus. We hypothesize that an insecticidal double-stranded (ds) RNA targeting western corn rootworm, Diabrotica virgifera virgifera, ha...
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.
Directory of Open Access Journals (Sweden)
Chalanda Evans
2016-06-01
Full Text Available Young women from hereditary breast and ovarian cancer (HBOC families face a series of medical decisions regarding their cancer risk management and integrating this information into their life planning. This presents unique medical and psychosocial challenges that exist without comprehensive intervention. To help lay the groundwork for intervention, we conducted a qualitative study among young women from HBOC families (N = 12; Mean age = 22 and cancer genetic counselors (N = 12 to explicate domains most critical to caring for this population. Women and counselors were interviewed by telephone. The predominant interview themes included preventative care planning and risk management, decision making around the pros and cons of cancer risk assessment, medical management, and psychosocial stresses experienced. Young women endorsed psychosocial stress significantly more frequently than did counselors. Both groups noted the short- and long-term decision making challenges and the support and conflict engendered among familial relationships. Our results suggest young women value the support they receive from their families and their genetic counselors, but additional, external supports are needed to facilitate adaptation to HBOC risk. In feedback interviews focused on intervention planning with a subset of these young women (N = 9, they endorsed the predominant interview themes discovered as important intervention content, a structure that would balance discussion of medical information and psychosocial skill-building that could be tailored to the young women’s needs, and delivery by trained peers familiar with HBOC risk.
Class II HLA interactions modulate genetic risk for multiple sclerosis
Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil
2016-01-01
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388
International Nuclear Information System (INIS)
Conrad, J.
1978-03-01
In view of the growing importance assumed in recent years by scientific work on the calculation, quantification, evaluation and acceptance as well as behavior in the face of risks in general and more specifically, the risks of large industrial plants, the report attempts to provide a survey of the current situation, results and evaluation of this new branch of research, risk assessment. The emphasis of the report is on the basic discussion and criticism of the theoretical and methodological approaches used in the field of risk assessment (section 3). It is concerned above all with - methodical problems of determining and quantifying risks (3.1) - questions of the possibility of risk evaluation and comp arison (3.1, 3.2) - the premises of normative and empirical studies on decision making under risk (3.2, 3.3) - investigations into society's acceptance of risks involved in the introduction of new technologies (3.4) - attempts to combine various aspects of the field of risk assessment in a unified concept (3.5, 3.6, 3.7). Because risk assessment is embedded in the framework of decision theory and technology assessment, it can be implicitly evaluated at a more general level within this framework, as far as its possibilities and weaknesses of method and application are concerned (section 4). Sections 2 and 5 deal with the social context of origin and utilization of risk assessment. Finally, an attempt is made at a summary indicating the possible future development of risk assessment. (orig./HP) [de
Women-specific risk factors for heart failure: A genetic approach.
van der Kemp, Jet; van der Schouw, Yvonne T; Asselbergs, Folkert W; Onland-Moret, N Charlotte
2018-03-01
Heart failure is a complex disease, which is presented differently by men and women. Several studies have shown that reproductive factors, such as age at natural menopause, parity and polycystic ovarian syndrome (PCOS), may play a role in the development of heart failure. Shared genetics may provide clues to underlying mechanisms; however, this has never been examined. Therefore, the aim of the current study was to explore whether any reproductive factor is potentially related to heart failure in women, based on genetic similarities. Conducting a systematic literature review, single nucleotide polymorphisms (SNPs) associated with reproductive factors, heart failure and its risk factors were extracted from recent genome-wide association studies. We tested whether there was any overlap between the SNPs and their proxies of reproductive risk factors with those known for heart failure or its risk factors. In total, 520 genetic variants were found that are associated with reproductive factors, namely age at menarche, age at natural menopause, menstrual cycle length, PCOS, preeclampsia, preterm delivery and spontaneous dizygotic twinning. For heart failure and associated phenotypes, 25 variants were found. Genetic variants for reproductive factors did not overlap with those for heart failure. However, age at menarche, gestational diabetes and PCOS were found to be genetically linked to risk factors for heart failure, such as atrial fibrillation, diabetes and smoking. Corresponding implicated genes, such as TNNI3K, ErbB3, MKL2, MTNR1B and PRKD1, may explain the associations between reproductive factors and heart failure. Exact effector mechanisms of these genes remain to be investigated further. Copyright © 2017. Published by Elsevier B.V.
Risk assessment and risk management of mycotoxins.
2012-01-01
Risk assessment is the process of quantifying the magnitude and exposure, or probability, of a harmful effect to individuals or populations from certain agents or activities. Here, we summarize the four steps of risk assessment: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Risk assessments using these principles have been conducted on the major mycotoxins (aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, and zearalenone) by various regulatory agencies for the purpose of setting food safety guidelines. We critically evaluate the impact of these risk assessment parameters on the estimated global burden of the associated diseases as well as the impact of regulatory measures on food supply and international trade. Apart from the well-established risk posed by aflatoxins, many uncertainties still exist about risk assessments for the other major mycotoxins, often reflecting a lack of epidemiological data. Differences exist in the risk management strategies and in the ways different governments impose regulations and technologies to reduce levels of mycotoxins in the food-chain. Regulatory measures have very little impact on remote rural and subsistence farming communities in developing countries, in contrast to developed countries, where regulations are strictly enforced to reduce and/or remove mycotoxin contamination. However, in the absence of the relevant technologies or the necessary infrastructure, we highlight simple intervention practices to reduce mycotoxin contamination in the field and/or prevent mycotoxin formation during storage.
Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis.
Kohler, Christian G; Richard, Jan A; Brensinger, Colleen M; Borgmann-Winter, Karin E; Conroy, Catherine G; Moberg, Paul J; Gur, Ruben C; Gur, Raquel E; Calkins, Monica E
2014-05-15
A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Biosafety Risk Assessment Methodology
Energy Technology Data Exchange (ETDEWEB)
Caskey, Susan Adele [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). International Biological Threat Reduction Program; Gaudioso, Jennifer M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). International Biological Threat Reduction Program; Salerno, Reynolds Mathewson [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). International Biological Threat Reduction Program; Wagner, Stefan M. [Public Health Agency of Canada, Winnipeg, MB (Canada). Canadian Science Centre for Human and Animal Health (CSCHAH); Shigematsu, Mika [National Inst. of Infectious Diseases (NIID), Tokyo (Japan); Risi, George [Infectious Disease Specialists, P.C, Missoula, MT (United States); Kozlovac, Joe [US Dept. of Agriculture (USDA)., Beltsville, MD (United States); Halkjaer-Knudsen, Vibeke [Statens Serum Inst., Copenhagen (Denmark); Prat, Esmeralda [Bayer CropScience, Monheim am Rhein (Germany)
2010-10-01
Laboratories that work with biological agents need to manage their safety risks to persons working the laboratories and the human and animal community in the surrounding areas. Biosafety guidance defines a wide variety of biosafety risk mitigation measures, which include measures which fall under the following categories: engineering controls, procedural and administrative controls, and the use of personal protective equipment; the determination of which mitigation measures should be used to address the specific laboratory risks are dependent upon a risk assessment. Ideally, a risk assessment should be conducted in a manner which is standardized and systematic which allows it to be repeatable and comparable. A risk assessment should clearly define the risk being assessed and avoid over complication.
Biotechnological uses of RNAi in plants: risk assessment considerations.
Casacuberta, Josep M; Devos, Yann; du Jardin, Patrick; Ramon, Matthew; Vaucheret, Hervé; Nogué, Fabien
2015-03-01
RNAi offers opportunities to generate new traits in genetically modified (GM) plants. Instead of expressing novel proteins, RNAi-based GM plants reduce target gene expression. Silencing of off-target genes may trigger unintended effects, and identifying these genes would facilitate risk assessment. However, using bioinformatics alone is not reliable, due to the lack of genomic data and insufficient knowledge of mechanisms governing mRNA-small (s)RNA interactions. Copyright © 2014 Elsevier Ltd. All rights reserved.
Shahid, Saleem Ullah; Shabana; Cooper, Jackie A; Beaney, Katherine E; Li, Kawah; Rehman, Abdul; Humphries, Steve E
2017-03-01
Conventional coronary artery disease (CAD) risk factors like age, gender, blood lipids, hypertension and smoking have been the basis of CAD risk prediction algorithms, but provide only modest discrimination. Genetic risk score (GRS) may provide improved discrimination over and above conventional risk factors. Here we analyzed the genetic risk of CAD in subjects from Pakistan, using a GRS of 21 variants in 18 genes and examined whether the GRS is associated with blood lipid levels. 625 (405 cases and 220 controls) subjects were genotyped for variants, NOS3 rs1799983, SMAD3 rs17228212, APOB rs1042031, LPA rs3798220, LPA rs10455872, SORT1 rs646776, APOE rs429358, GLUL rs10911021, FTO rs9939609, MIA3 rs17465637, CDKN2Ars10757274, DAB2IP rs7025486, CXCL12 rs1746048, ACE rs4341, APOA5 rs662799, CETP rs708272, MRAS rs9818870, LPL rs328, LPL rs1801177, PCSK9 rs11591147 and APOE rs7412 by TaqMan and KASPar allele discrimination techniques. Individually, the single SNPs were not associated with CAD except APOB rs1042031 and FTO rs993969 (p = 0.01 and 0.009 respectively). However, the combined GRS of 21 SNPs was significantly higher in cases than controls (19.37 ± 2.56 vs. 18.47 ± 2.45, p = 2.9 × 10 -5 ), and compared to the bottom quintile, CAD risk in the top quintile of the GRS was 2.96 (95% CI 1.71-5.13). Atherogenic blood lipids showed significant positive association with GRS. The GRS was quantitatively associated with CAD risk and showed association with blood lipid levels, suggesting that the mechanism of these variants is likely to be, in part at least, through creating an atherogenic lipid profile in subjects carrying high numbers of risk alleles. Copyright © 2017 Elsevier B.V. All rights reserved.
Common Gene Variants Account for Most Genetic Risk for Autism
... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...
Jung, Su Yon; Sobel, Eric M; Papp, Jeanette C; Zhang, Zuo-Feng
2017-04-26
Impaired glucose metabolism-related genetic variants and traits likely interact with obesity and related lifestyle factors, influencing postmenopausal breast and colorectal cancer (CRC), but their interconnected pathways are not fully understood. By stratifying via obesity and lifestyles, we partitioned the total effect of glucose metabolism genetic variants on cancer risk into two putative mechanisms: 1) indirect (risk-associated glucose metabolism genetic variants mediated by glucose metabolism traits) and 2) direct (risk-associated glucose metabolism genetic variants through pathways other than glucose metabolism traits) effects. Using 16 single-nucleotide polymorphisms (SNPs) associated with glucose metabolism and data from 5379 postmenopausal women in the Women's Health Initiative Harmonized and Imputed Genome-Wide Association Studies, we retrospectively assessed the indirect and direct effects of glucose metabolism-traits (fasting glucose, insulin, and homeostatic model assessment-insulin resistance [HOMA-IR]) using two quantitative tests. Several SNPs were associated with breast cancer and CRC risk, and these SNP-cancer associations differed between non-obese and obese women. In both strata, the direct effect of cancer risk associated with the SNP accounted for the majority of the total effect for most SNPs, with roughly 10% of cancer risk due to the SNP that was from an indirect effect mediated by glucose metabolism traits. No apparent differences in the indirect (glucose metabolism-mediated) effects were seen between non-obese and obese women. It is notable that among obese women, 50% of cancer risk was mediated via glucose metabolism trait, owing to two SNPs: in breast cancer, in relation to GCKR through glucose, and in CRC, in relation to DGKB/TMEM195 through HOMA-IR. Our findings suggest that glucose metabolism genetic variants interact with obesity, resulting in altered cancer risk through pathways other than those mediated by glucose metabolism traits.
Risk perception among women receiving genetic counseling: a population-based follow-up study
DEFF Research Database (Denmark)
Mikkelsen, Ellen M; Sunde, Lone; Johansen, Christoffer
2007-01-01
-up study of 213 women who received genetic counseling for hereditary breast and ovarian cancer, 319 women who underwent mammography (Reference Group I), and a random sample of 1070 women from the general population (Reference Group II). RESULTS: Women who received genetic counseling decreased...... counseling, compared to a reduction of 5% (p=0.03) and 2% (p=0.01) in Reference Groups I and II, respectively. Risk communicated only in words, inaccurate risk perception at baseline, and presence of a familial mutation appeared to be predictors of inaccurate risk perception 12 months after counseling......BACKGROUND: We aimed to explore the impact of genetic counseling on perceived personal lifetime risk of breast cancer, the accuracy of risk perception, and possible predictors of inaccurate risk perception 1 year following counseling. METHODS: We conducted a population-based prospective follow...
Michael J. Firko; Jane Leslie Hayes
1990-01-01
Quantitative genetic studies of resistance can provide estimates of genetic parameters not available with other types of genetic analyses. Three methods are discussed for estimating the amount of additive genetic variation in resistance to individual insecticides and subsequent estimation of heritability (h2) of resistance. Sibling analysis and...
2007 TOXICOLOGY AND RISK ASSESSMENT ...
EPA has announced The 2007 Toxicology and Risk Assessment Conference Cincinnati Marriott North, West Chester (Cincinnati), OHApril 23- 26, 2007 - Click to register!The Annual Toxicology and Risk Assessment Conference is a unique meeting where several Government Agencies come together to discuss toxicology and risk assessment issues that are not only of concern to the government, but also to a broader audience including academia and industry. The theme of this year's conference is Emerging Issues and Challenges in Risk Assessment and the preliminary agenda includes: Plenary Sessions and prominent speakers (tentative) include: Issues of Emerging Chemical ContaminantsUncertainty and Variability in Risk Assessment Use of Mechanistic data in IARC evaluationsParallel Sessions:Uncertainty and Variability in Dose-Response Assessment Recent Advances in Toxicity and Risk Assessment of RDX The Use of Epidemiologic Data for Risk Assessment Applications Cumulative Health Risk Assessment:
Directory of Open Access Journals (Sweden)
Isabelle Schrauwen
Full Text Available Necrotizing meningoencephalitis (NME affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7 and 15 (chr15:53338796A>G, p = 1.5×10-7. Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively. This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.
Schrauwen, Isabelle; Barber, Renee M; Schatzberg, Scott J; Siniard, Ashley L; Corneveaux, Jason J; Porter, Brian F; Vernau, Karen M; Keesler, Rebekah I; Matiasek, Kaspar; Flegel, Thomas; Miller, Andrew D; Southard, Teresa; Mariani, Christopher L; Johnson, Gayle C; Huentelman, Matthew J
2014-01-01
Necrotizing meningoencephalitis (NME) affects toy and small breed dogs causing progressive, often fatal, inflammation and necrosis in the brain. Genetic risk loci for NME previously were identified in pug dogs, particularly associated with the dog leukocyte antigen (DLA) class II complex on chromosome 12, but have not been investigated in other susceptible breeds. We sought to evaluate Maltese and Chihuahua dogs, in addition to pug dogs, to identify novel or shared genetic risk factors for NME development. Genome-wide association testing of single nucleotide polymorphisms (SNPs) in Maltese dogs with NME identified 2 regions of genome-wide significance on chromosomes 4 (chr4:74522353T>A, p = 8.1×10-7) and 15 (chr15:53338796A>G, p = 1.5×10-7). Haplotype analysis and fine-mapping suggests that ILR7 and FBXW7, respectively, both important for regulation of immune system function, could be the underlying associated genes. Further evaluation of these regions and the previously identified DLA II locus across all three breeds, revealed an enrichment of nominal significant SNPs associated with chromosome 15 in pug dogs and DLA II in Maltese and Chihuahua dogs. Meta-analysis confirmed effect sizes the same direction in all three breeds for both the chromosome 15 and DLA II loci (p = 8.6×10-11 and p = 2.5×10-7, respectively). This suggests a shared genetic background exists between all breeds and confers susceptibility to NME, but effect sizes might be different among breeds. In conclusion, we identified the first genetic risk factors for NME development in the Maltese, chromosome 4 and chromosome 15, and provide evidence for a shared genetic risk between breeds associated with chromosome 15 and DLA II. Last, DLA II and IL7R both have been implicated in human inflammatory diseases of the central nervous system such as multiple sclerosis, suggesting that similar pharmacotherapeutic targets across species should be investigated.
Directory of Open Access Journals (Sweden)
Hagiwara N
2017-12-01
Full Text Available Nobuko Hagiwara Division of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, University of California, Davis, CA, USA Abstract: The steadily falling costs of genome sequencing, coupled with the growing number of genetic tests with proven clinical validity, have made the use of genetic testing more common in clinical practice. This development has necessitated nongeneticist physicians, especially primary care physicians, to become more responsible for assessing genetic risks for their patients. Providing undergraduate medical students a solid foundation in genomic medicine, therefore, has become all the more important to ensure the readiness of future physicians in applying genomic medicine to their patient care. In order to further enhance the effectiveness of instructing practical skills in medical genetics, the emphasis of active learning modules in genetics curriculum at medical schools has increased in recent years. This is because of the general acceptance of a better efficacy of active learner-centered pedagogy over passive lecturer-centered pedagogy. However, an objective standard to evaluate students’ skill levels in genomic medicine achieved by active learning is currently missing. Recently, entrustable professional activities (EPAs in genomic medicine have been proposed as a framework for developing physician competencies in genomic medicine. EPAs in genomic medicine provide a convenient guideline for not only developing genomic medicine curriculum but also assessing students’ competency levels in practicing genomic medicine. In this review, the efficacy of different types of active learning modules reported for medical genetics curricula is discussed using EPAs in genomic medicine as a common evaluation standard for modules’ learning outcomes. The utility of the EPAs in genomic medicine for designing active learning modules in undergraduate medical genetics curricula is also discussed. Keywords
How the EPA conducts risk assessment to protect human health and the environment. Several assessments are included with the guidelines, models, databases, state-based RSL Tables, local contacts and framework documents used to perform these assessments.
Exploration Health Risks: Probabilistic Risk Assessment
Rhatigan, Jennifer; Charles, John; Hayes, Judith; Wren, Kiley
2006-01-01
Maintenance of human health on long-duration exploration missions is a primary challenge to mission designers. Indeed, human health risks are currently the largest risk contributors to the risks of evacuation or loss of the crew on long-duration International Space Station missions. We describe a quantitative assessment of the relative probabilities of occurrence of the individual risks to human safety and efficiency during space flight to augment qualitative assessments used in this field to date. Quantitative probabilistic risk assessments will allow program managers to focus resources on those human health risks most likely to occur with undesirable consequences. Truly quantitative assessments are common, even expected, in the engineering and actuarial spheres, but that capability is just emerging in some arenas of life sciences research, such as identifying and minimize the hazards to astronauts during future space exploration missions. Our expectation is that these results can be used to inform NASA mission design trade studies in the near future with the objective of preventing the higher among the human health risks. We identify and discuss statistical techniques to provide this risk quantification based on relevant sets of astronaut biomedical data from short and long duration space flights as well as relevant analog populations. We outline critical assumptions made in the calculations and discuss the rationale for these. Our efforts to date have focussed on quantifying the probabilities of medical risks that are qualitatively perceived as relatively high risks of radiation sickness, cardiac dysrhythmias, medically significant renal stone formation due to increased calcium mobilization, decompression sickness as a result of EVA (extravehicular activity), and bone fracture due to loss of bone mineral density. We present these quantitative probabilities in order-of-magnitude comparison format so that relative risk can be gauged. We address the effects of
Assessment of genetic diversity among sixty bread wheat ( Triticum ...
African Journals Online (AJOL)
Assessment of genetic diversity among wheat cultivars is important to ensure that a continuous pool of cultivars with varying desirable traits is maintained. In view of this, a molecular study was conducted to assess the genetic diversity of sixty wheat cultivars using sixty microsatellite markers. Amplified alleles from each ...
Subjective versus objective risk in genetic counseling for hereditary breast and/or ovarian cancers
Directory of Open Access Journals (Sweden)
Sperduti Isabella
2009-12-01
Full Text Available Abstract Background Despite the fact that genetic counseling in oncology provides information regarding objective risks, it can be found a contrast between the subjective and objective risk. The aims of this study were to evaluate the accuracy of the perceived risk compared to the objective risk estimated by the BRCApro computer model and to evaluate any associations between medical, demographic and psychological variables and the accuracy of risk perception. Methods 130 subjects were given medical-demographic file, Cancer and Genetic Risk Perception, Hospital Anxiety-Depression Scale. It was also computed an objective evaluation of the risk by the BRCApro model. Results The subjective risk was significantly higher than objective risk. The risk of tumour was overestimated by 56%, and the genetic risk by 67%. The subjects with less cancer affected relatives significantly overestimated their risk of being mutation carriers and made a more innacurate estimation than high risk subjects. Conclusion The description of this sample shows: general overestimation of the risk, inaccurate perception compared to BRCApro calculation and a more accurate estimation in those subjects with more cancer affected relatives (high risk subjects. No correlation was found between the levels of perception of risk and anxiety and depression. Based on our findings, it is worth pursuing improved communication strategies about the actual cancer and genetic risk, especially for subjects at "intermediate and slightly increased risk" of developing an hereditary breast and/or ovarian cancer or of being mutation carrier.
Application Form for NCI Cancer Genetics Services Directory
Professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others) may fill out this application form to be listed in the National Cancer Institute's Cancer Genetics Services Directory.
Inclusion Criteria for NCI Cancer Genetics Services Directory
Professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others) must meet these criteria before applying to be listed in the National Cancer Institute's Cancer Genetics Services Directory.
Genetic Analysis of Elevated Mastitis Risk Based on Mastitis Indicator Data
DEFF Research Database (Denmark)
Sørensen, Lars Peter; Løvendahl, Peter
Whole-genome sequences and multiple trait phenotypes from large numbers of individuals will soon be available. Well established statistical modeling approaches enable the genetic analyses of complex trait phenotypes while accounting for a variety of additive and non-additive genetic mechanisms....... These modeling approaches have proven to be highly useful to determine population genetic parameters as well as prediction of genetic risk or value. We present statistical modelling approaches that use prior biological information for evaluating the collective action of sets of genetic variants. We have applied...
Sariaslan, A; Larsson, H; Fazel, S
2016-09-01
Patients diagnosed with psychotic disorders (for example, schizophrenia and bipolar disorder) have elevated risks of committing violent acts, particularly if they are comorbid with substance misuse. Despite recent insights from quantitative and molecular genetic studies demonstrating considerable pleiotropy in the genetic architecture of these phenotypes, there is currently a lack of large-scale studies that have specifically examined the aetiological links between psychotic disorders and violence. Using a sample of all Swedish individuals born between 1958 and 1989 (n=3 332 101), we identified a total of 923 259 twin-sibling pairs. Patients were identified using the National Patient Register using validated algorithms based on International Classification of Diseases (ICD) 8-10. Univariate quantitative genetic models revealed that all phenotypes (schizophrenia, bipolar disorder, substance misuse, and violent crime) were highly heritable (h(2)=53-71%). Multivariate models further revealed that schizophrenia was a stronger predictor of violence (r=0.32; 95% confidence interval: 0.30-0.33) than bipolar disorder (r=0.23; 0.21-0.25), and large proportions (51-67%) of these phenotypic correlations were explained by genetic factors shared between each disorder, substance misuse, and violence. Importantly, we found that genetic influences that were unrelated to substance misuse explained approximately a fifth (21%; 20-22%) of the correlation with violent criminality in bipolar disorder but none of the same correlation in schizophrenia (Pbipolar disordergenetically similar phenotypes as the latter sources may include aetiologically important clues. Clinically, these findings underline the importance of assessing risk of different phenotypes together and integrating interventions for psychiatric disorders, substance misuse, and violence.
'Battling my biology': psychological effects of genetic testing for risk of weight gain.
Meisel, S F; Wardle, J
2014-04-01
The availability of genetic tests for multifactorial conditions such as obesity raises concerns that higher-risk results could lead to fatalistic reactions or lower-risk results to complacency. No study has investigated the effects of genetic test feedback for the risk of obesity in non-clinical samples. The present study explored psychological and behavioral reactions to genetic test feedback for a weight related gene (FTO) in a volunteer sample (n = 18) using semi-structured interviews. Respondents perceived the gene test result as scientifically objective; removing some of the emotion attached to the issue of weight control. Those who were struggling with weight control reported relief of self-blame. There was no evidence for either complacency or fatalism; all respondents emphasized the importance of lifestyle choices in long-term weight management, although they recognized the role of both genes and environment. Regardless of the test result, respondents evaluated the testing positively and found it motivating and informative. Genetic test feedback for risk of weight gain may offer psychological benefits beyond its objectively limited clinical utility. As the role of genetic counselors is likely to expand, awareness of reasons for genetic testing for common, complex conditions and reactions to the test result is important.
Molecular profiling--a tool for addressing emerging gaps in the comparative risk assessment of GMOs.
Heinemann, Jack A; Kurenbach, Brigitta; Quist, David
2011-10-01
Assessing the risks of genetically modified organisms (GMOs) is required by both international agreement and domestic legislation. Many view the use of the "omics" tools for profiling classes of molecules as useful in risk assessment, but no consensus has formed on the need or value of these techniques for assessing the risks of all GMOs. In this and many other cases, experts support case-by-case use of molecular profiling techniques for risk assessment. We review the latest research on the applicability and usefulness of molecular profiling techniques for GMO risk assessment. As more and more kinds of GMOs and traits are developed, broader use of molecular profiling in a risk assessment may be required to supplement the comparative approach to risk assessment. The literature-based discussions on the use of profiling appear to have settled on two findings: 1. profiling techniques are reliable and relevant, at least no less so than other techniques used in risk assessment; and 2. although not required routinely, regulators should be aware of when they are needed. The dismissal of routine molecular profiling may be confusing to regulators who then lack guidance on when molecular profiling might be worthwhile. Molecular profiling is an important way to increase confidence in risk assessments if the profiles are properly designed to address relevant risks and are applied at the correct stage of the assessment. Copyright © 2011 Elsevier Ltd. All rights reserved.
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.
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
Martin, Joanna; Hamshere, Marian L; Stergiakouli, Evangelia; O'Donovan, Michael C; Thapar, Anita
2014-10-15
Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of traits in the general population. Epidemiological and twin studies suggest that ADHD frequently co-occurs with and shares genetic susceptibility with autism spectrum disorder (ASD) and ASD-related traits. The aims of this study were to determine whether a composite of common molecular genetic variants, previously found to be associated with clinically diagnosed ADHD, predicts ADHD and ASD-related traits in the general population. Polygenic risk scores were calculated in the Avon Longitudinal Study of Parents and Children (ALSPAC) population sample (N = 8229) based on a discovery case-control genome-wide association study of childhood ADHD. Regression analyses were used to assess whether polygenic scores predicted ADHD traits and ASD-related measures (pragmatic language abilities and social cognition) in the ALSPAC sample. Polygenic scores were also compared in boys and girls endorsing any (rating ≥ 1) ADHD item (n = 3623). Polygenic risk for ADHD showed a positive association with ADHD traits (hyperactive-impulsive, p = .0039; inattentive, p = .037). Polygenic risk for ADHD was also negatively associated with pragmatic language abilities (p = .037) but not with social cognition (p = .43). In children with a rating ≥ 1 for ADHD traits, girls had a higher polygenic score than boys (p = .003). These findings provide molecular genetic evidence that risk alleles for the categorical disorder of ADHD influence hyperactive-impulsive and attentional traits in the general population. The results further suggest that common genetic variation that contributes to ADHD diagnosis may also influence ASD-related traits, which at their extreme are a characteristic feature of ASD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Defining a Contemporary Ischemic Heart Disease Genetic Risk Profile Using Historical Data.
Mosley, Jonathan D; van Driest, Sara L; Wells, Quinn S; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Denny, Josh C; Roden, Dan M
2016-12-01
Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype. We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=-0.44, P=0.005), high-density lipoprotein (rG=-0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors. The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease. © 2016 American Heart Association, Inc.
Coronary artery disease-associated genetic variants and biomarkers of inflammation
DEFF Research Database (Denmark)
Christiansen, Morten Krogh; Larsen, Sanne Bøjet; Nyegaard, Mette
2017-01-01
score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. RESULTS:The minor allele (G) (CAD risk allele) of rs2075650......INTRODUCTION:Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD...
On the genetic risk after high dose radioiodine therapy with regard to the gonadal dose
International Nuclear Information System (INIS)
Ehrenheim, C.; Hauswirth, C.; Fitschen, J.; Martin, E.; Oetting, G.; Hundeshagen, H.
1997-01-01
Aim: The genetic risk for the offspring of patients treated with high doses of radioiodine was to be assessed with special regard to the gonadal dose caused by diagnostic and therapeutic procedures. Methods: 41 young females (aged between 19 and 39 years) and four young males (aged 26 to 36 years) treated with radioiodine because of a thyroid carcinoma were interviewed by use of a questionnaire. The course of pregnancy and birth history could be documented as well as the congenital and developmental conditions of 56 children. Results: The amount of radioactivity applied for therapy and whole body scans ranged over 4,144 and 35,15 GBq I-131; the individual gonadal dose was calculated based on the MIRD model and ranged over 0,2 and 2,2 Sv (0,51 Sv at a mean). The period of time between the last radioiodine application and confinement was at least 9 months, not exceeding 14 years. As to the course of pregnancy and birth two early abortions, one extrauterine gravidity and one premature birth due to an insufficiency of the placenta were stated. In one case a chromosomal translocation 7/14 occured as a genetic defect which lead to an interruption. The children's development was unconspicuous except of two cases of neurodermatitis as well as multiple allergies and an early closure of the anterior fontanelle in one child each. Conclusion: Although the genetic risk is supposed to increase with the gonadal dose achieved (doubling dose 1 Sv) and the increased risk of any congenital anomaly was calculated as about 13% at a mean in our patients, the rate of genetic determined diseases was not elevated (1,8% or 1/57). Thus, no increase of genetic defects or congenital malformations was reported in a total of 408 children described in the literature and in our group. (orig.) [de
[Safety assessment of foods derived from genetically modified plants].
Pöting, A; Schauzu, M
2010-06-01
The placing of genetically modified plants and derived food on the market falls under Regulation (EC) No. 1829/2003. According to this regulation, applicants need to perform a safety assessment according to the Guidance Document of the Scientific Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA), which is based on internationally agreed recommendations. This article gives an overview of the underlying legislation as well as the strategy and scientific criteria for the safety assessment, which should generally be based on the concept of substantial equivalence and carried out in relation to an unmodified conventional counterpart. Besides the intended genetic modification, potential unintended changes also have to be assessed with regard to potential adverse effects for the consumer. All genetically modified plants and derived food products, which have been evaluated by EFSA so far, were considered to be as safe as products derived from the respective conventional plants.
Cheng, Yue; Yu, Chengxiao; Huang, Mingtao; Du, Fangzhi; Song, Ci; Ma, Zijian; Zhai, Xiangjun; Yang, Yuan; Liu, Jibin; Bei, Jin-Xin; Jia, Weihua; Jin, Guangfu; Li, Shengping; Zhou, Weiping; Liu, Jianjun; Dai, Juncheng; Hu, Zhibin
2017-10-01
Observational studies show an association between telomere length and Hepatocellular carcinoma (HCC) risk, but the relationship is controversial. Particularly, it remains unclear whether the association is due to confounding or biases inherent in conventional epidemiological studies. Here, we applied Mendelian randomization approach to evaluate whether telomere length is causally associated with HCC risk. Individual-level data were from HBV-related HCC Genome-wide association studies (1,538 HBV positive HCC patients and 1,465 HBV positive controls). Genetic risk score, as proxy for actual measured telomere length, derived from nine telomere length-associated genetic variants was used to evaluate the effect of telomere length on HCC risk. We observed a significant risk signal between genetically increased telomere length and HBV-related HCC risk (OR=2.09, 95% CI 1.32-3.31, P=0.002). Furthermore, a U-shaped curve was fitted by the restricted cubic spline curve, which indicated that either short or long telomere length would increase HCC risk (P=0.0022 for non-linearity test). Subgroup analysis did not reveal significant heterogeneity between different age, gender, smoking status and drinking status groups. Our results indicated that a genetic background that favors longer or shorter telomere length may increase HBV-related HCC risk-a U-shaped association. Copyright © 2017 Elsevier Ltd. All rights reserved.
Genetic risk from diagnostic X-ray procedures
International Nuclear Information System (INIS)
Stephan, G.
1980-01-01
This essay introduces epidemiologic studies concerned with the question whether diagnostic X-ray procedures might be the cause of an increased genetic risk. All studies have selected Down's syndrome (mongolism) as genetic indicator. They indiscriminately present the opinion of the respective author. Approximately one half of the studies conclude that radiation exposure will not influence the spontaneous incidence of Down's syndrome in diagnostics, the other half finds a positive relationship between frequent radiation exposure and the incidence of the syndrome. For various reasons, explained in detail, the results of the studies under discussion are suitable for forming hypotheses, but should not be viewed as providing evidence. (orig.) [de
Genetic and other risk factors for suicidal ideation and the relationship with depression.
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.
Hanford Site's Integrated Risk Assessment Program: No-intervention risk assessment
International Nuclear Information System (INIS)
Mahaffey, J.A.; Dukelow, J.S. Jr.; Stenner, R.D.
1994-08-01
The long-term goal of the Integrated Risk Assessment program (IRAP) is to estimate risks to workers, the public, organizations, and groups with reserved rights to Site access, the ecosystem, and natural resources to aid in managing environmental restoration and waste management at the Hanford Site. For each of these, information is needed about current risks, risks during cleanup, and endstate risks. The objective is three-fold: to determine if and when to remediate, and to what extent; to identify information unavailable but needed to make better cleanup decisions; to establish technology performance criteria for achieving desired cleanup levels; to understand costs and benefits of activities from a Site-wide perspective. The no-intervention risk, assessment is the initial evaluation of public health risks conducted under IRAP. The objective is to identify types of activities that the US Department of Energy (DOE) must accomplish for closure of the Hanford Site, defined as no further DOE intervention. There are two primary conclusions from the no-intervention risk assessment. First, some maintenance and operations activities at Hanford must be continued to protect the public from grave risks. However, when large Hanford expenditures are compared to cleanup progress, funds expended for maintenance and operations must be put in proper perspective. Second, stakeholder's emphasis on public risks at Hanford, as indicated by remediation priorities, are not in line with those estimated. The focus currently is on compliance with regulations, and on dealing with issues which are visible to stakeholders
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...
Directory of Open Access Journals (Sweden)
Yiming Hu
2017-06-01
Full Text Available Accurate prediction of disease risk based on genetic factors is an important goal in human genetics research and precision medicine. Advanced prediction models will lead to more effective disease prevention and treatment strategies. Despite the identification of thousands of disease-associated genetic variants through genome-wide association studies (GWAS in the past decade, accuracy of genetic risk prediction remains moderate for most diseases, which is largely due to the challenges in both identifying all the functionally relevant variants and accurately estimating their effect sizes. In this work, we introduce PleioPred, a principled framework that leverages pleiotropy and functional annotations in genetic risk prediction for complex diseases. PleioPred uses GWAS summary statistics as its input, and jointly models multiple genetically correlated diseases and a variety of external information including linkage disequilibrium and diverse functional annotations to increase the accuracy of risk prediction. Through comprehensive simulations and real data analyses on Crohn's disease, celiac disease and type-II diabetes, we demonstrate that our approach can substantially increase the accuracy of polygenic risk prediction and risk population stratification, i.e. PleioPred can significantly better separate type-II diabetes patients with early and late onset ages, illustrating its potential clinical application. Furthermore, we show that the increment in prediction accuracy is significantly correlated with the genetic correlation between the predicted and jointly modeled diseases.
This course is aimed at providing an overview of the fundamental guiding principles and general methods used in chemical risk assessment. Chemical risk assessment is a complex and ever-evolving process. These principles and methods have been organized by the National Research Cou...
Genetics of variation in HOMA-IR and cardiovascular risk factors in Mexican-Americans.
Voruganti, V Saroja; Lopez-Alvarenga, Juan C; Nath, Subrata D; Rainwater, David L; Bauer, Richard; Cole, Shelley A; Maccluer, Jean W; Blangero, John; Comuzzie, Anthony G
2008-03-01
Insulin resistance is a major biochemical defect underlying the pathogenesis of cardiovascular disease (CVD). Mexican-Americans are known to have an unfavorable cardiovascular profile. Thus, the aim of this study was to investigate the genetic effect on variation in HOMA-IR and to evaluate its genetic correlations with other phenotypes related to risk of CVD in Mexican-Americans. The homeostatic model assessment method (HOMA-IR) is one of several approaches that are used to measure insulin resistance and was used here to generate a quantitative phenotype for genetic analysis. For 644 adults who had participated in the San Antonio Family Heart Study (SAFHS), estimates of genetic contribution were computed using a variance components method implemented in SOLAR. Traits that exhibited significant heritabilities were body mass index (BMI) (h (2) = 0.43), waist circumference (h (2) = 0.48), systolic blood pressure (h (2) = 0.30), diastolic blood pressure (h (2) = 0.21), pulse pressure (h (2) = 0.32), triglycerides (h (2) = 0.51), LDL cholesterol (h (2) = 0.31), HDL cholesterol (h (2) = 0.24), C-reactive protein (h (2) = 0.17), and HOMA-IR (h (2) = 0.33). A genome-wide scan for HOMA-IR revealed significant evidence of linkage on chromosome 12q24 (close to PAH (phenylalanine hydroxylase), LOD = 3.01, p HOMA-IR with BMI (rho (G) = 0.36), waist circumference (rho (G) = 0.47), pulse pressure (rho (G) = 0.39), and HDL cholesterol (rho (G) = -0.18). Identification of significant linkage for HOMA-IR on chromosome 12q replicates previous family-based studies reporting linkage of phenotypes associated with type 2 diabetes in the same chromosomal region. Significant genetic correlations between HOMA-IR and phenotypes related to CVD risk factors suggest that a common set of gene(s) influence the regulation of these phenotypes.
International Nuclear Information System (INIS)
Morris, J.M.
1994-01-01
The following paper is an informal summary of salient points made in the presentation entitled open-quotes An Integrated Risk Assessment Approach: Risk Assessment in the Programmatic Environmental Impact Statement (PEIS).close quotes. This presentation was given at the U.S. DOE Integrated Planning Workshop in Denver, Colorado on June 2, 1994. Integrated decision analysis is very important in environmental restoration and waste management in the evaluation of such things as land use planning, waste load forecasting, cost analyses, and technology development activities. Integrated risk assessment is an approach that addresses multiple components of risk, including: risks from surplus facilities as well as typical environmental restoration sites, risks to the public, risks to workers, ecological risk, risks before, during and after remediation activities, and others
Directory of Open Access Journals (Sweden)
Chinyere V Nzeduru
Full Text Available Transgenes encoding for insecticidal crystal (Cry proteins from the soil-dwelling bacterium Bacillus Thuringiensis have been widely introduced into Genetically Modified (GM crops to confer protection against insect pests. Concern that these transgenes may also harm beneficial or otherwise valued insects (so-called Non Target Organisms, NTOs represents a major element of the Environmental Risk Assessments (ERAs used by all countries prior to commercial release. Compiling a comprehensive list of potentially susceptible NTOs is therefore a necessary part of an ERA for any Cry toxin-containing GM crop. In partly-characterised and biodiverse countries, NTO identification is slowed by the need for taxonomic expertise and time to enable morphological identifications. This limitation represents a potentially serious barrier to timely adoption of GM technology in some developing countries. We consider Bt Cry1A cowpea (Vigna unguiculata in Nigeria as an exemplar to demonstrate how COI barcoding can provide a simple and cost-effective means of addressing this problem. Over a period of eight weeks, we collected 163 insects from cowpea flowers across the agroecological and geographic range of the crop in Nigeria. These individuals included 32 Operational Taxonomic Units (OTUs spanning four Orders and that could mostly be assigned to genus or species level. They included 12 Lepidopterans and two Coleopterans (both potentially sensitive to different groups of Cry proteins. Thus, barcode-assisted diagnoses were highly harmonised across groups (typically to genus or species level and so were insensitive to expertise or knowledge gaps. Decisively, the entire study was completed within four months at a cost of less than 10,000 US$. The broader implications of the findings for food security and the capacity for safe adoption of GM technology are briefly explored.
The relation of risk assessment and health impact assessment
DEFF Research Database (Denmark)
Ádám, Balázs; Gulis, Gabriel
2013-01-01
than assessing a present situation. As part of this process, however, methods applied in risk assessment are used. Risk assessment typically characterises relation of a well-defined risk factor to a well-defined health outcome. Within HIA usually several individual risk assessments are needed...... of the causal chain from the proposal through related health determinants and risk factors to health outcomes. The stepwise analysis, systematic prioritization and consideration of horizontal interactions between the causal pathways make it feasible to use widely recognized risk assessment methods in the HIA......The level and distribution of health risks in a society is substantially influenced by measures of various policies, programmes or projects. Risk assessment can evaluate the nature, likelihood and severity of an adverse effect. Health impact assessment (HIA) provides similar function when used...
Assessment of cardiovascular risk.
LENUS (Irish Health Repository)
Cooney, Marie Therese
2010-10-01
Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?
Structured Parenting of Toddlers at High versus Low Genetic Risk: Two Pathways to Child Problems
Leve, Leslie D.; Harold, Gordon T.; Ge, Xiaojia; Neiderhiser, Jenae M.; Shaw, Daniel; Scaramella, Laura V.; Reiss, David
2009-01-01
Objective: Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. We used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for…
National Research Council Canada - National Science Library
O'Neill, Suzanne
2001-01-01
..., Shattuck-Eidens, Frank, and BRCAPRO models. Questionnaires assessing psychological status, and knowledge and attitudes about breast cancer, cancer risk counseling, and genetic testing were used to identify predictors of referral uptake...
New concepts in risk assessment for patients with radiological treatment
International Nuclear Information System (INIS)
Tautz, M.; Brandt, G.A.
1986-01-01
In radiation risk assessment it must be differentiated between somatic and genetic effect on the one hand as well as between stochastic and non-stochastic effect on the other. According to definitions of the ICRP report 26 the limit for the dose equivalent of all tissues prevents non-stochastic radiation effects. With stochastic radiation effects probably exist no threshold doses; therefore the ALARA principle must be applied concerning radiation protection. The individual risk by stochastic radiation effects in its linear, linear-quadratic and quadratic extrapolations, respectively, is discussed in detail. The effective stochastic dose equivalent (H/sub eff/) as well as collective dose and collective damage are outlined
Increased genetic risk for obesity in premature coronary artery disease.
Cole, Christopher B; Nikpay, Majid; Stewart, Alexandre F R; McPherson, Ruth
2016-04-01
There is ongoing controversy as to whether obesity confers risk for CAD independently of associated risk factors including diabetes mellitus. We have carried out a Mendelian randomization study using a genetic risk score (GRS) for body mass index (BMI) based on 35 risk alleles to investigate this question in a population of 5831 early onset CAD cases without diabetes mellitus and 3832 elderly healthy control subjects, all of strictly European ancestry, with adjustment for traditional risk factors (TRFs). We then estimated the genetic correlation between these BMI and CAD (rg) by relating the pairwise genetic similarity matrix to a phenotypic covariance matrix between these two traits. GRSBMI significantly (P=2.12 × 10(-12)) associated with CAD status in a multivariate model adjusted for TRFs, with a per allele odds ratio (OR) of 1.06 (95% CI 1.042-1.076). The addition of GRSBMI to TRFs explained 0.75% of CAD variance and yielded a continuous net recombination index of 16.54% (95% CI=11.82-21.26%, P<0.0001). To test whether GRSBMI explained CAD status when adjusted for measured BMI, separate models were constructed in which the score and BMI were either included as covariates or not. The addition of BMI explained ~1.9% of CAD variance and GRSBMI plus BMI explained 2.65% of CAD variance. Finally, using bivariate restricted maximum likelihood analysis, we provide strong evidence of genome-wide pleiotropy between obesity and CAD. This analysis supports the hypothesis that obesity is a causal risk factor for CAD.
CCL3L1-CCR5 genotype improves the assessment of AIDS Risk in HIV-1-infected individuals.
Kulkarni, Hemant; Agan, Brian K; Marconi, Vincent C; O'Connell, Robert J; Camargo, Jose F; He, Weijing; Delmar, Judith; Phelps, Kenneth R; Crawford, George; Clark, Robert A; Dolan, Matthew J; Ahuja, Sunil K
2008-09-08
Whether vexing clinical decision-making dilemmas can be partly addressed by recent advances in genomics is unclear. For example, when to initiate highly active antiretroviral therapy (HAART) during HIV-1 infection remains a clinical dilemma. This decision relies heavily on assessing AIDS risk based on the CD4+ T cell count and plasma viral load. However, the trajectories of these two laboratory markers are influenced, in part, by polymorphisms in CCR5, the major HIV coreceptor, and the gene copy number of CCL3L1, a potent CCR5 ligand and HIV-suppressive chemokine. Therefore, we determined whether accounting for both genetic and laboratory markers provided an improved means of assessing AIDS risk. In a prospective, single-site, ethnically-mixed cohort of 1,132 HIV-positive subjects, we determined the AIDS risk conveyed by the laboratory and genetic markers separately and in combination. Subjects were assigned to a low, moderate or high genetic risk group (GRG) based on variations in CCL3L1 and CCR5. The predictive value of the CCL3L1-CCR5 GRGs, as estimated by likelihood ratios, was equivalent to that of the laboratory markers. GRG status also predicted AIDS development when the laboratory markers conveyed a contrary risk. Additionally, in two separate and large groups of HIV+ subjects from a natural history cohort, the results from additive risk-scoring systems and classification and regression tree (CART) analysis revealed that the laboratory and CCL3L1-CCR5 genetic markers together provided more prognostic information than either marker alone. Furthermore, GRGs independently predicted the time interval from seroconversion to CD4+ cell count thresholds used to guide HAART initiation. The combination of the laboratory and genetic markers captures a broader spectrum of AIDS risk than either marker alone. By tracking a unique aspect of AIDS risk distinct from that captured by the laboratory parameters, CCL3L1-CCR5 genotypes may have utility in HIV clinical management
Hollis, Chris; Groom, Madeleine J; Das, Debasis; Calton, Tim; Bates, Alan T; Andrews, Hayley K; Jackson, Georgina M; Liddle, Peter F
2008-10-01
Controversy exists regarding whether young people at risk for schizophrenia are at increased risk of adverse mental effects of cannabis use. We examined cannabis use and mental health functioning in three groups of young people aged 14-21; 36 non-psychotic siblings of adolescents with schizophrenia (genetic high risk group), 25 adolescents with attention deficit hyperactivity disorder (ADHD) and 72 healthy controls. The groups were sub-divided into 'users' and 'non-users' of cannabis based on how often they had used cannabis previously. Mental health functioning was quantified by creating a composite index derived from scores on the Schizotypal Personality Questionnaire (SPQ), Strengths and Difficulties Questionnaire (SDQ) and Global Assessment of Function (GAF). A significant positive association between cannabis use and mental health disturbance was confined to young people at genetic high risk for schizophrenia. To determine whether the relationship was specific to particular dimensions of mental health function, a second composite index was created based on scores from the SPQ Disorganisation and SDQ hyperactivity-inattention sub-scales. Again, there was a significant positive association between cannabis use and factor scores which was specific to the genetic high risk group. There was a trend for this association to be negative in the ADHD group (p=0.07). The findings support the view that young people at genetic high risk for schizophrenia are particularly vulnerable to mental health problems associated with cannabis use. Further research is needed to investigate the basis of relationships between cannabis and mental health in genetically vulnerable individuals.
Institute of Scientific and Technical Information of China (English)
Jinsong Tang; Fan He; Fengyu Zhang; Yin Yao Shugart; Chunyu Liu; Yanqing Tang; Raymond C.K.Chan; Chuan-Yue Wang; Yong-Gang Yao; Xiaogang Chen; Yu Fan; Hong Li; Qun Xiang; Deng-Feng Zhang; Zongchang Li; Ying He; Yanhui Liao; Ya Wang
2017-01-01
Schizophrenia is a common disorder with a high heritability,but its genetic architecture is still elusive.We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia.Eight non-synonymous DNMs (including one splicing site) were identified and shared by twins,which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN,p.S2506T mutation in GCN1L1,IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis.By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes,we were able to distill genetic alterations in several schizophrenia risk genes,including GAD1,PLXNA2,RELN and FEZ1.Four inherited copy number variations (CNVs;including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families,respectively.Most of families carried both missense DNMs and inherited risk variants,which might suggest that DNMs,inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility.Our results support that schizophrenia is caused by a combination of multiple genetic factors,with each DNM/variant showing a relatively small effect size.
Directory of Open Access Journals (Sweden)
Eda Kılıç Çoban
2015-09-01
Full Text Available Stroke is defined as a focal or at times global neurological impairment of sudden onset, that lasts more than 24 hours or that leads to death. The nonmodifiable risk factors for stroke include age, race, gender and acquired risk factors include smoking, hypertension, diabetes and obesity. Previous studies have shown that these mentioned risk factors might be responsible for approximately 50% of patients presenting stroke. However for the remaining half of the stroke patients no risk factors could be detected and genetics might be responsible for this group. In this manuscript we would like to present 2 cases who were being followed-up with the rare genetic syndromes as Marfan syndrome and Robinow syndrome respectively. These patients presented to our clinic with stroke and no identifiable risk factors other than these genetic syndromes could be detected. By this case-series we would like to further discuss the relationship between genetic syndromes and stroke.
Friesen, Phoebe; Lawrence, Ryan E; Brucato, Gary; Girgis, Ragy R; Dixon, Lisa
2016-11-01
Genetic tests for schizophrenia could introduce both risks and benefits. Little is known about the hopes and expectations of young adults at clinical high-risk for psychosis concerning genetic testing for schizophrenia, despite the fact that these youth could be among those highly affected by such tests. We conducted semistructured interviews with 15 young adults at clinical high-risk for psychosis to ask about their interest, expectations, and hopes regarding genetic testing for schizophrenia. Most participants reported a high level of interest in genetic testing for schizophrenia, and the majority said they would take such a test immediately if it were available. Some expressed far-reaching expectations for a genetic test, such as predicting symptom severity and the timing of symptom onset. Several assumed that genetic testing would be accompanied by interventions to prevent schizophrenia. Participants anticipated mixed reactions on finding out they had a genetic risk for schizophrenia, suggesting that they might feel both a sense of relief and a sense of hopelessness. We suggest that genetic counseling could play an important role in counteracting a culture of genetic over-optimism and helping young adults at clinical high-risk for psychosis understand the limitations of genetic testing. Counseling sessions could also invite individuals to explore how receiving genetic risk information might impact their well-being, as early evidence suggests that some psychological factors help individuals cope, whereas others heighten distress related to genetic test results.
Ionizing radiation and genetic risks
International Nuclear Information System (INIS)
Sankaranarayanan, K.; Wassom, J.S.
2005-01-01
Recent estimates of genetic risks from exposure of human populations to ionizing radiation are those presented in the 2001 report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). These estimates incorporate two important concepts, namely, the following: (1) most radiation-induced mutations are DNA deletions, often encompassing multiple genes, but only a small proportion of the induced deletions is compatible with offspring viability; and (2) the viability-compatible deletions induced in germ cells are more likely to manifest themselves as multi-system developmental anomalies rather than as single gene disorders. This paper: (a) pursues these concepts further in the light of knowledge of mechanisms of origin of deletions and other rearrangements from two fields of contemporary research: repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian somatic cells and human molecular genetics; and (b) extends them to deletions induced in the germ cell stages of importance for radiation risk estimation, namely, stem cell spermatogonia in males and oocytes in females. DSB repair studies in somatic cells have elucidated the roles of two mechanistically distinct pathways, namely, homologous recombination repair (HRR) that utilizes extensive sequence homology and non-homologous end-joining (NHEJ) that requires little or no homology at the junctions. A third process, single-strand annealing (SSA), which utilizes short direct repeat sequences, is considered a variant of HRR. HRR is most efficient in late S and G 2 phases of the cell cycle and is a high fidelity mechanism. NHEJ operates in all cell cycle phases, but is especially important in G 1 . In the context of radiation-induced DSBs, NHEJ is error-prone. SSA is also an error-prone mechanism and its role is presumably similar to that of HRR. Studies in human molecular genetics have demonstrated that the occurrence of large deletions, duplications or other rearrangements
Ionizing radiation and genetic risks
Energy Technology Data Exchange (ETDEWEB)
Sankaranarayanan, K. [Department of Toxicogenetics, Leiden University Medical Centre, Sylvius Laboratories, Wassenaarseweg 72, 2333 AL Leiden (Netherlands)]. E-mail: sankaran@lumc.nl; Wassom, J.S. [YAHSGS, LLC, Richland, WA 99352 (United States); Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37830 (United States)
2005-10-15
Recent estimates of genetic risks from exposure of human populations to ionizing radiation are those presented in the 2001 report of the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). These estimates incorporate two important concepts, namely, the following: (1) most radiation-induced mutations are DNA deletions, often encompassing multiple genes, but only a small proportion of the induced deletions is compatible with offspring viability; and (2) the viability-compatible deletions induced in germ cells are more likely to manifest themselves as multi-system developmental anomalies rather than as single gene disorders. This paper: (a) pursues these concepts further in the light of knowledge of mechanisms of origin of deletions and other rearrangements from two fields of contemporary research: repair of radiation-induced DNA double-strand breaks (DSBs) in mammalian somatic cells and human molecular genetics; and (b) extends them to deletions induced in the germ cell stages of importance for radiation risk estimation, namely, stem cell spermatogonia in males and oocytes in females. DSB repair studies in somatic cells have elucidated the roles of two mechanistically distinct pathways, namely, homologous recombination repair (HRR) that utilizes extensive sequence homology and non-homologous end-joining (NHEJ) that requires little or no homology at the junctions. A third process, single-strand annealing (SSA), which utilizes short direct repeat sequences, is considered a variant of HRR. HRR is most efficient in late S and G{sub 2} phases of the cell cycle and is a high fidelity mechanism. NHEJ operates in all cell cycle phases, but is especially important in G{sub 1}. In the context of radiation-induced DSBs, NHEJ is error-prone. SSA is also an error-prone mechanism and its role is presumably similar to that of HRR. Studies in human molecular genetics have demonstrated that the occurrence of large deletions, duplications or other
Baumgart, Leigh A; Postula, Kristen J Vogel; Knaus, William A
2016-04-01
Personal and family health histories remain important independent risk factors for cancer; however they are currently not being well collected or used effectively. Health Heritage was designed to address this need. The purpose of this study was to validate the ability of Health Heritage to identify patients appropriate for further genetic evaluation and to accurately stratify cancer risk. A retrospective chart review was conducted on 100 random patients seen at an adult genetics clinic presenting with concern for an inherited predisposition to cancer. Relevant personal and family history obtained from the patients' medical records was entered into Health Heritage. Recommendations by Health Heritage were compared to national guidelines of eligibility for genetic evaluation. Agreement between Health Heritage referral for genetic evaluation and guideline eligibility for genetic evaluation was 97% (sensitivity 98% and specificity 88%). Risk stratification for cancer was also compared between Health Heritage and those documented by a geneticist. For patients at increased risk for breast, ovarian, or colorectal cancer as determined by the geneticist, risk stratification by Health Heritage agreed 90, 93, and 75%, respectively. Discordances in risk stratification were attributed to both complex situations better handled by the geneticist and Health Heritage's adherence to incorporating all information into its algorithms. Health Heritage is a clinically valid tool to identify patients appropriate for further genetic evaluation and to encourage them to confirm the assessment and management recommendations with cancer genetic experts. Health Heritage also provides an estimate of cancer risk that is complementary to a genetics team.
Bodenant, Marie; Kuulasmaa, Kari; Wagner, Aline; Kee, Frank; Palmieri, Luigi; Ferrario, Marco M; Montaye, Michèle; Amouyel, Philippe; Dallongeville, Jean
2011-10-01
Excess fat accumulates in the subcutaneous and visceral adipose tissue compartments. We tested the hypothesis that indicators of visceral adiposity, namely, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), are better predictors of stroke risk than body mass index (BMI). The association of BMI, WC, WHR, and WHtR with stroke was assessed in 31,201 men and 23,516 women, free of vascular disease at baseline, from the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) study. During a mean follow-up of 11 years, 1130 strokes were recorded. Relative risks (95% CI) were calculated by Cox regression after stratification for center and adjustment for age, smoking, educational level, alcohol consumption, hypertension, diabetes, total cholesterol, high-density lipoprotein cholesterol, and BMI and model fit was assessed using log-likelihoods. BMI, WC, WHR, and WHtR were associated with the risk of stroke in men. After full adjustment including BMI, the relative risks for stroke remained significant for WC (1.19 [1.02 to 1.34] per 1 SD increase in WC), WHR (1.14 [1.03 to 1.26]), and WHtR (1.50 [1.28 to 1.77]). Among women, the extent of the associations with stroke risk was similar for WHtR (1.31 [1.04 to 1.65]), WC (1.19 [0.96 to 1.47]), and WHR (1.08 [0.97 to 1.22]). Further analyses by World Health Organization obesity categories showed that WC, WHR, and WHtR were associated with the risk of stroke also in lean men and women (BMI<25 kg/m2), independently of confounders, cardiovascular risk factors, and BMI. Indicators of abdominal adiposity, especially WHtR, are more strongly associated with stroke risk than BMI. These results emphasize the importance of measuring abdominal adiposity, especially in lean subjects.
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.
Sussner, K M; Edwards, T A; Thompson, H S; Jandorf, L; Kwate, N O; Forman, A; Brown, K; Kapil-Pair, N; Bovbjerg, D H; Schwartz, M D; Valdimarsdottir, H B
2011-01-01
Due to disparities in the use of genetic services, there has been growing interest in examining beliefs and attitudes related to genetic testing for breast and/or ovarian cancer risk among women of African descent. However, to date, few studies have addressed critical cultural variations among this minority group and their influence on such beliefs and attitudes. We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City. All participants completed the following previously validated measures: (a) the multi-group ethnic identity measure (including ethnic search and affirmation subscales) and other-group orientation for ethnic identity, (b) centrality to assess racial identity, and (c) Africentrism to measure cultural identity. Perceived benefits and barriers related to genetic testing included: (1) pros/advantages (including family-related pros), (2) cons/disadvantages (including family-related cons, stigma and confidentiality concerns), and (3) concerns about abuses of genetic testing. In multivariate analyses, several ethnic identity elements showed significant, largely positive relationships to perceived benefits about genetic testing for breast and/or ovarian cancer risk, the exception being ethnic search, which was positively associated with cons/disadvantages, in general, and family-related cons/disadvantages. Racial identity (centrality) showed a significant association with confidentiality concerns. Cultural identity (Africentrism) was not related to perceived benefits and/or barriers. Ethnic and racial identity may influence perceived benefits and barriers
Factors Motivating Individuals to Consider Genetic Testing for Type 2 Diabetes Risk Prediction.
Directory of Open Access Journals (Sweden)
Jennifer Wessel
Full Text Available The purpose of this study was to identify attitudes and perceptions of willingness to participate in genetic testing for type 2 diabetes (T2D risk prediction in the general population. Adults (n = 598 were surveyed on attitudes about utilizing genetic testing to predict future risk of T2D. Participants were recruited from public libraries (53%, online registry (37% and a safety net hospital emergency department (10%. Respondents were 37 ± 11 years old, primarily White (54%, female (69%, college educated (46%, with an annual income ≥$25,000 (56%. Half of participants were interested in genetic testing for T2D (52% and 81% agreed/strongly agreed genetic testing should be available to the public. Only 57% of individuals knew T2D is preventable. A multivariate model to predict interest in genetic testing was adjusted for age, gender, recruitment location and BMI; significant predictors were motivation (high perceived personal risk of T2D [OR = 4.38 (1.76, 10.9]; family history [OR = 2.56 (1.46, 4.48]; desire to know risk prior to disease onset [OR = 3.25 (1.94, 5.42]; and knowing T2D is preventable [OR = 2.11 (1.24, 3.60], intention (if the cost is free [OR = 10.2 (4.27, 24.6]; and learning T2D is preventable [OR = 5.18 (1.95, 13.7] and trust of genetic testing results [OR = 0.03 (0.003, 0.30]. Individuals are interested in genetic testing for T2D risk which offers unique information that is personalized. Financial accessibility, validity of the test and availability of diabetes prevention programs were identified as predictors of interest in T2D testing.
Directory of Open Access Journals (Sweden)
Amanda A Fox
Full Text Available BACKGROUND: Postoperative ventricular dysfunction (VnD occurs in 9-20% of coronary artery bypass graft (CABG surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery. METHODS: A genome-wide association study identified single nucleotide polymorphisms (SNPs associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for ≥2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed. RESULTS: Over 100 SNPs were associated with VnD (P2.1 of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.
Inflammatory Genetic Markers of Prostate Cancer Risk
International Nuclear Information System (INIS)
Tindall, Elizabeth A.; Hayes, Vanessa M.; Petersen, Desiree C.
2010-01-01
Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk
Inflammatory Genetic Markers of Prostate Cancer Risk
Energy Technology Data Exchange (ETDEWEB)
Tindall, Elizabeth A.; Hayes, Vanessa M. [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia); University of New South Wales, Kensington Campus, Sydney, NSW 2052 (Australia); Petersen, Desiree C., E-mail: dpetersen@ccia.unsw.edu.au [Cancer Genetics Group, Children’s Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, PO Box 81, Randwick, NSW 2031 (Australia)
2010-06-08
Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates that inflammation is important in prostate cancer pathogenesis. In this review, we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk.
Genetic risk load according to the site of intracranial aneurysms
van 't Hof, Femke N. G.; Kurki, Mitja I.; Kleinloog, Rachel; de Bakker, Paul I. W.; von Und Zu Fraunberg, Mikael; Jääskeläinen, Juha E.; Gaál, Emília I.; Lehto, Hanna; Kivisaari, Riku; Laakso, Aki; Niemelä, Mika; Hernesniemi, Juha; Brouwer, Matthijs C.; van de Beek, Diederik; Rinkel, Gabriël J. E.; Ruigrok, Ynte M.
2014-01-01
We investigated whether risk alleles of single nucleotide polymorphisms associated with intracranial aneurysm (IA) are enriched in patients with familial IA, IA located at the middle cerebral artery (MCA), or IA rupture at a younger age. In this case-only study, we calculated genetic risk scores
Directory of Open Access Journals (Sweden)
Su Yon Jung
Full Text Available Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E, influencing postmenopausal colorectal cancer (CRC risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs in genes related to insulin-like growth factor-I (IGF-I/ insulin resistance (IR traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.
Fanshawe, Thomas R; Prevost, A Toby; Roberts, J Scott; Green, Robert C; Armstrong, David; Marteau, Theresa M
2008-09-01
This paper explores whether and how the behavioral impact of genotype disclosure can be disentangled from the impact of numerical risk estimates generated by genetic tests. Secondary data analyses are presented from a randomized controlled trial of 162 first-degree relatives of Alzheimer's disease (AD) patients. Each participant received a lifetime risk estimate of AD. Control group estimates were based on age, gender, family history, and assumed epsilon4-negative apolipoprotein E (APOE) genotype; intervention group estimates were based upon the first three variables plus true APOE genotype, which was also disclosed. AD-specific self-reported behavior change (diet, exercise, and medication use) was assessed at 12 months. Behavior change was significantly more likely with increasing risk estimates, and also more likely, but not significantly so, in epsilon4-positive intervention group participants (53% changed behavior) than in control group participants (31%). Intervention group participants receiving epsilon4-negative genotype feedback (24% changed behavior) and control group participants had similar rates of behavior change and risk estimates, the latter allowing assessment of the independent effects of genotype disclosure. However, collinearity between risk estimates and epsilon4-positive genotypes, which engender high-risk estimates, prevented assessment of the independent effect of the disclosure of an epsilon4 genotype. Novel study designs are proposed to determine whether genotype disclosure has an impact upon behavior beyond that of numerical risk estimates.
Hagiwara, Nobuko
2017-01-01
The steadily falling costs of genome sequencing, coupled with the growing number of genetic tests with proven clinical validity, have made the use of genetic testing more common in clinical practice. This development has necessitated nongeneticist physicians, especially primary care physicians, to become more responsible for assessing genetic risks for their patients. Providing undergraduate medical students a solid foundation in genomic medicine, therefore, has become all the more important to ensure the readiness of future physicians in applying genomic medicine to their patient care. In order to further enhance the effectiveness of instructing practical skills in medical genetics, the emphasis of active learning modules in genetics curriculum at medical schools has increased in recent years. This is because of the general acceptance of a better efficacy of active learner-centered pedagogy over passive lecturer-centered pedagogy. However, an objective standard to evaluate students' skill levels in genomic medicine achieved by active learning is currently missing. Recently, entrustable professional activities (EPAs) in genomic medicine have been proposed as a framework for developing physician competencies in genomic medicine. EPAs in genomic medicine provide a convenient guideline for not only developing genomic medicine curriculum but also assessing students' competency levels in practicing genomic medicine. In this review, the efficacy of different types of active learning modules reported for medical genetics curricula is discussed using EPAs in genomic medicine as a common evaluation standard for modules' learning outcomes. The utility of the EPAs in genomic medicine for designing active learning modules in undergraduate medical genetics curricula is also discussed.
Risk analysis of bioprocesses based on genetically modified bacteria. Pathway and exposure modeling
Energy Technology Data Exchange (ETDEWEB)
Rein, A.; Bittens, M. [Tuebingen Univ. (Germany). Zentrum fuer Angewandte Geowissenschaften
2003-07-01
For soils contaminated with polychlorinated biphenyls (PCBs), a plant-microorganism system for in situ - bioremediation has been developed. It consists of genetically modified microorganisms (GMOs) in conjunction with plant roots. The GMOs are Pseudomonas fluorescens strains which are genetically engineered to degrade PCB congeners in situ. Their metabolism requires root exudates and is therefore tightly coupled to plant rhizospheres. Compared to wild type organisms, the genetically modified bacteria develop a specificity to PCB as a substrate and therefore foster biodegradation in a more efficient way. To evaluate the efficiency and impact of this bioremediation system for potential field application, lysimeter tests are carried out. The lysimeters are filled with contaminated soil from a PCB release site in Denmark and planted with GMO inoculated plants. On the basis of these experiments, a detailed risk analysis is carried out to obtain conclusions to field-conditions (potential deliberate GMO-release). A qualitative and quantitative assessment of actual or potential effects is performed, addressing transport, fate and exposure of PCBs, GMOs and specific degradation products in different environmental compartments. (orig.)
Information needs for risk assessment
Energy Technology Data Exchange (ETDEWEB)
DeRosa, C.T.; Choudhury, H.; Schoeny, R.S.
1990-12-31
Risk assessment can be thought of as a conceptual approach to bridge the gap between the available data and the ultimate goal of characterizing the risk or hazard associated with a particular environmental problem. To lend consistency to and to promote quality in the process, the US Environmental Protection Agency (EPA) published Guidelines for Risk Assessment of Carcinogenicity, Developmental Toxicity, Germ Cell Mutagenicity and Exposure Assessment, and Risk Assessment of Chemical Mixtures. The guidelines provide a framework for organizing the information, evaluating data, and for carrying out the risk assessment in a scientifically plausible manner. In the absence of sufficient scientific information or when abundant data are available, the guidelines provide alternative methodologies that can be employed in the risk assessment. 4 refs., 3 figs., 2 tabs.
Probabilistic risk assessment as an aid to risk management
International Nuclear Information System (INIS)
Garrick, B.J.
1982-01-01
Probabilistic risk assessments are providing important insights into nuclear power plant safety. Their value is two-fold: first as a means of quantifying nuclear plant risk including contributors to risk, and second as an aid to risk management. A risk assessment provides an analytical plant model that can be the basis for performing meaningful decision analyses for controlling safety. It is the aspect of quantitative risk management that makes probabilistic risk assessment an important technical discipline of the future
Directory of Open Access Journals (Sweden)
Fesinmeyer Megan D
2013-01-01
Full Text Available Abstract Background Although smoking behavior is known to affect body mass index (BMI, the potential for smoking to influence genetic associations with BMI is largely unexplored. Methods As part of the ‘Population Architecture using Genomics and Epidemiology (PAGE’ Consortium, we investigated interaction between genetic risk factors associated with BMI and smoking for 10 single nucleotide polymorphisms (SNPs previously identified in genome-wide association studies. We included 6 studies with a total of 56,466 subjects (16,750 African Americans (AA and 39,716 European Americans (EA. We assessed effect modification by testing an interaction term for each SNP and smoking (current vs. former/never in the linear regression and by stratified analyses. Results We did not observe strong evidence for interactions and only observed two interactions with p-values TMEM18, the risk allele (C was associated with BMI only among AA females who were former/never smokers (β = 0.018, p = 0.002, vs. current smokers (β = 0.001, p = 0.95, pinteraction = 0.10. For rs9939609/FTO, the A allele was more strongly associated with BMI among current smoker EA females (β = 0.017, p = 3.5x10-5, vs. former/never smokers (β = 0.006, p = 0.05, pinteraction = 0.08. Conclusions These analyses provide limited evidence that smoking status may modify genetic effects of previously identified genetic risk factors for BMI. Larger studies are needed to follow up our results. Clinical Trial Registration NCT00000611
Making sense of genetic uncertainty: the role of religion and spirituality.
White, Mary T
2009-02-15
This article argues that to the extent that religious and spiritual beliefs can help people cope with genetic uncertainty, a limited spiritual assessment may be appropriate in genetic counseling. The article opens by establishing why genetic information is inherently uncertain and why this uncertainty can be medically, morally, and spiritually problematic. This is followed by a review of the range of factors that can contribute to risk assessments, including a few heuristics commonly used in responses to uncertainty. The next two sections summarize recent research on the diverse roles of religious and spiritual beliefs in genetic decisions and challenges to conducting spiritual assessments in genetic counseling. Based on these findings, religious and spiritual beliefs are posited as serving essentially as a heuristic that some people will utilize in responding to their genetic risks. In the interests of helping such clients make informed decisions, a limited spiritual assessment is recommended and described. Some of the challenges and risks associated with this limited assessment are discussed. Since some religious and spiritual beliefs can conflict with the values of medicine, some decisions will remain problematic. (c) 2009 Wiley-Liss, Inc.
Ferreira-Gonzalez, Andrea; Teutsch, Steven; Williams, Marc S; Au, Sylvia M; Fitzgerald, Kevin T; Miller, Paul Steven; Fomous, Cathy
2008-09-01
As genetic testing technology is integrated into healthcare, increasingly detailed information about individual and population genetic variation is available to patients and providers. Health professionals use genetic testing to diagnose or assess the risk of disease in individuals, families and populations and to guide healthcare decisions. Consumers are beginning to explore personalized genomic services in an effort to learn more about their risk for common diseases. Scientific and technological advances in genetic testing, as with any newly introduced medical technology, present certain challenges to existing frameworks of oversight. In addition, the growing use of genetic testing will require a significant investment in evidence-based assessments to understand the validity and utility of these tests in clinical and personal decisionmaking. To optimize the use of genetic testing in healthcare, all sectors of the oversight system need to be strengthened and yet remain flexible in order to adapt to advances that will inevitably increase the range of genetic tests and methodologies.
Risks assessment - role of pre-existing genetic variation
International Nuclear Information System (INIS)
Unrau, P.; Doerffer, K.
1996-01-01
Previously published research on the epidemiology and molecular basis of genetic or congenital diseases and their occurrence in certain 'ethnic' or isolated populations is discussed to show the significance of consanguinity and 'ethnicity' as contributing factors. A statistical study aiming to correlate malformations with absolutely any environmental factor may miss the significance of defects in a gene pool. This consideration has an obvious significance for the nuclear industry. For example, carriers of Fanconi's anemia appear to have an increased tendency to develop acute myelogenous leukemia. The authors indicate the difficulty in finding a definite molecular basis even for simple Mendelian monogenic disorders such as Tay-Sachs disease. 12 refs., 4 tabs
Wenbo, Li; Congxia, Bai; Hui, Liu
2017-08-30
To quantitatively assess the role of heredity and environmental factors in myopia based on the family with enough exposed to risk from myopic environment for establishment of environmental and genetic index (EGI). A pedigree analysis unit was defined as one child (university student), father, and mother. Information pertaining to visual acuity, experience in participating in the college entrance examination in mainland of China (regarded as a strong environmental risk for myopia), and occupation for pedigree analysis units were obtained. The difference between effect of both genetic and environmental factors (myopia prevalence in children with two myopic parents) and environmental factors (myopia prevalence in children of whom neither parent was myopic) was defined as the EGI. Multiple regression analysis was performed for 114 pedigree using diopters of father, mother, average diopters in parents, maximum and minimum diopters in father and mother as variables. A total of 353 farmers and 162 farmer families were used as a control group. A distinct difference in myopia rate (96.2% versus 57.7%) was observed for children from parents with myopia and parents without myopia (EGI=0.385). The maximum diopter was included to regression equation which was statistically significant. The prevalence of myopia was 9.9% in the farmer. The prevalence in children is similar between the farmer and other families. A new genetic rule that myopia in children was directly related with maximum diopters in father and mother may be suggested. Environmental factors may play a leading role in the formation of myopia. Copyright © 2017 Elsevier B.V. All rights reserved.
Rueth, Natasha M; McMahon, Melissa; Arrington, Amanda K; Swenson, Karen; Leach, Joseph; Tuttle, Todd M
2011-09-01
Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. Our objective was to determine the prevalence of BRCA testing among women undergoing bilateral prophylactic mastectomy (BPM) and to review the characteristics of women who choose BPM within a metropolitan setting. We retrospectively reviewed records of women who underwent BPM in the absence of cancer within 2 health care systems that included 5 metropolitan hospitals. Women with invasive carcinoma or ductal carcinoma in situ (DCIS) were excluded; neither lobular carcinoma in situ (LCIS) nor atypical hyperplasia (AH) were exclusion criteria. We collected demographic information and preoperative screening and risk assessment, BRCA testing, reconstruction, and associated cancer risk-reducing surgery data. We compared women who underwent BRCA testing to those not tested. From January 2002 to July 2009, a total of 71 BPMs were performed. Only 25 women (35.2%) had preoperative BRCA testing; 88% had a BRCA mutation. Compared with tested women, BRCA nontested women were significantly older (39.1 vs. 49.2 years, P < 0.001), had significantly more preoperative biopsies and mammograms and had fewer previous or simultaneous cancer risk-reducing surgery (oophorectomy). Among BRCA nontested women, common indications for BPM were family history of breast cancer (n = 21, 45.6%) or LCIS or AH (n = 16, 34.8%); 9 nontested women (19.6%) chose BPM based on exclusively on cancer-risk anxiety or personal preference. Most women who underwent BPM did not receive preoperative genetic testing. Further studies are needed to corroborate our findings in other geographic regions and practice settings.
Horak, Michael J; Rosenbaum, Eric W; Phillips, Samuel L; Kendrick, Daniel L; Carson, David; Clark, Pete L; Nickson, Thomas E
2015-01-01
As part of an ecological risk assessment, Roundup Ready 2 Yield® soybean (MON 89788) was compared to a conventional control soybean variety, A3244, for disease and arthropod damage, plant response to abiotic stress and cold, effects on succeeding plant growth (allelopathic effects), plant response to a bacterial symbiont, and effects on the ability of seed to survive and volunteer in a subsequent growing season. Statistically significant differences between MON 89788 and A3244 were considered in the context of the genetic variation known to occur in soybean and were assessed for their potential impact on plant pest (weed) potential and adverse environmental impact. The results of these studies revealed no effects of the genetic modification that would result in increased pest potential or adverse environmental impact of MON 89788 compared with A3244. This paper illustrates how such characterization studies conducted in a range of environments where the crop is grown are used in an ecological risk assessment of the genetically modified (GM) crop. Furthermore, risk assessors and decision makers use this information when deciding whether to approve a GM crop for cultivation in-or grain import into-their country.
Chronic disease risk management: Combining genetic testing with ...
African Journals Online (AJOL)
Nutrigenetics has been used for decades to prevent rare monogenic disorders such as phenylketonuria. Gene-diet interaction can now also be targeted to prevent or reduce the risk of many chronic conditions long before clinical manifestation. This multidisciplinary approach unites conventional medicine with genetics and ...
Methodology of environmental risk assessment management
Directory of Open Access Journals (Sweden)
Saša T. Bakrač
2012-04-01
Full Text Available Successful protection of environment is mostly based on high-quality assessment of potential and present risks. Environmental risk management is a complex process which includes: identification, assessment and control of risk, namely taking measures in order to minimize the risk to an acceptable level. Environmental risk management methodology: In addition to these phases in the management of environmental risk, appropriate measures that affect the reduction of risk occurrence should be implemented: - normative and legal regulations (laws and regulations, - appropriate organizational structures in society, and - establishing quality monitoring of environment. The emphasis is placed on the application of assessment methodologies (three-model concept, as the most important aspect of successful management of environmental risk. Risk assessment methodology - European concept: The first concept of ecological risk assessment methodology is based on the so-called European model-concept. In order to better understand this ecological risk assessment methodology, two concepts - hazard and risk - are introduced. The European concept of environmental risk assessment has the following phases in its implementation: identification of hazard (danger, identification of consequences (if there is hazard, estimate of the scale of consequences, estimate of consequence probability and risk assessment (also called risk characterization. The European concept is often used to assess risk in the environment as a model for addressing the distribution of stressors along the source - path - receptor line. Risk assessment methodology - Canadian concept: The second concept of the methodology of environmental risk assessment is based on the so-called Canadian model-concept. The assessment of ecological risk includes risk arising from natural events (floods, extreme weather conditions, etc., technological processes and products, agents (chemical, biological, radiological, etc
Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review
Jing, Lijun; Su, Li; Ring, Brian Z.
2014-01-01
The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in ...
Derleth, Jason; Lobia, Marcus
2009-01-01
This slide presentation provides an overview of the attempt to develop and demonstrate a methodology for the comparative assessment of risks across the entire portfolio of NASA projects and assets. It includes information about strategic risk identification, normalizing strategic risks, calculation of relative risk score, and implementation options.
International Nuclear Information System (INIS)
Rimington, J.D.
1992-01-01
The paper begins by defining some terms, and then refer to a number of technical and other difficulties. Finally it attempts to set out why risk assessment is important and what its purposes are. 2) First, risk and risk assessment - what are they?. 3) Risk is a subject of universal significance. Life is very uncertain, and we can achieve no object or benefit in it except by approaching nearer to particular hazards which lie between us and our objects. That approach represents acceptance of risk. 4) Risk assessment is a way of systematising our approach to hazard with a view to determining what is more and what is less risky. It helps us in the end to diminish our exposure while obtaining whatever benefits we have in mind, or to optimise the risks and the benefits
Energy Technology Data Exchange (ETDEWEB)
Rimington, J D [Health and Safety Executive (United Kingdom)
1992-07-01
The paper begins by defining some terms, and then refer to a number of technical and other difficulties. Finally it attempts to set out why risk assessment is important and what its purposes are. 2) First, risk and risk assessment - what are they?. 3) Risk is a subject of universal significance. Life is very uncertain, and we can achieve no object or benefit in it except by approaching nearer to particular hazards which lie between us and our objects. That approach represents acceptance of risk. 4) Risk assessment is a way of systematising our approach to hazard with a view to determining what is more and what is less risky. It helps us in the end to diminish our exposure while obtaining whatever benefits we have in mind, or to optimise the risks and the benefits.
[Urban ecological risk assessment: a review].
Wang, Mei-E; Chen, Wei-Ping; Peng, Chi
2014-03-01
With the development of urbanization and the degradation of urban living environment, urban ecological risks caused by urbanization have attracted more and more attentions. Based on urban ecology principles and ecological risk assessment frameworks, contents of urban ecological risk assessment were reviewed in terms of driven forces, risk resources, risk receptors, endpoints and integrated approaches for risk assessment. It was suggested that types and degrees of urban economical and social activities were the driven forces for urban ecological risks. Ecological functional components at different levels in urban ecosystems as well as the urban system as a whole were the risk receptors. Assessment endpoints involved in changes of urban ecological structures, processes, functional components and the integrity of characteristic and function. Social-ecological models should be the major approaches for urban ecological risk assessment. Trends for urban ecological risk assessment study should focus on setting a definite protection target and criteria corresponding to assessment endpoints, establishing a multiple-parameter assessment system and integrative assessment approaches.
Supplementary data: Molecular assessment of genetic diversity in ...
Indian Academy of Sciences (India)
Molecular assessment of genetic diversity in cluster bean. (Cyamopsis tetragonoloba) genotypes. Rakesh Pathak, S. K. Singh, Manjit Singh and A. Henry. J. Genet. 89, 243–246. Figure 1. RAPD profile of 1–16 Cyamopsis tetragonoloba genotypes amplified with arbitrary primer OPA-16. Figure 2. RAPD profile of 17–32 ...
[Forensic assessment of violence risk].
Pujol Robinat, Amadeo; Mohíno Justes, Susana; Gómez-Durán, Esperanza L
2014-03-01
Over the last 20 years there have been steps forward in the field of scientific research on prediction and handling different violent behaviors. In this work we go over the classic concept of "criminal dangerousness" and the more current of "violence risk assessment". We analyze the evolution of such assessment from the practice of non-structured clinical expert opinion to current actuarial methods and structured clinical expert opinion. Next we approach the problem of assessing physical violence risk analyzing the HCR-20 (Assessing Risk for Violence) and we also review the classic and complex subject of the relation between mental disease and violence. One of the most problematic types of violence, difficult to assess and predict, is sexual violence. We study the different actuarial and sexual violence risk prediction instruments and in the end we advise an integral approach to the problem. We also go through partner violence risk assessment, describing the most frequently used scales, especially SARA (Spouse Assault Risk Assessment) and EPV-R. Finally we give practical advice on risk assessment, emphasizing the importance of having maximum information about the case, carrying out a clinical examination, psychopathologic exploration and the application of one of the described risk assessment scales. We'll have to express an opinion about the dangerousness/risk of future violence from the subject and some recommendations on the conduct to follow and the most advisable treatment. Copyright © 2014 Elsevier España, S.L. All rights reserved.
Eicher, John D.; Gruen, Jeffrey R.
2013-01-01
Dyslexia is a common pediatric disorder that affects 5-17% of schoolchildren in the United States. It is marked by unexpected difficulties in fluent reading despite adequate intelligence, opportunity, and instruction. Classically, neuropsychologists have studied dyslexia using a variety of neurocognitive batteries to gain insight into the specific deficits and impairments in affected children. Since dyslexia is a complex genetic trait with high heritability, analyses conditioned on performance on these neurocognitive batteries have been used to try to identify associated genes. This has led to some successes in identifying contributing genes, although much of the heritability remains unexplained. Additionally, the lack of relevant human brain tissue for analysis and the challenges of modeling a uniquely human trait in animals are barriers to advancing our knowledge of the underlying pathophysiology. In vivo imaging technologies, however, present new opportunities to examine dyslexia and reading skills in a clearly relevant context in human subjects. Recent investigations have started to integrate these imaging data with genetic data in attempts to gain a more complete and complex understanding of reading processes. In addition to bridging the gap from genetic risk variant to a discernible neuroimaging phenotype and ultimately to the clinical impairments in reading performance, the use of neuroimaging phenotypes will reveal novel risk genes and variants. In this article, we briefly discuss the genetic and imaging investigations and take an in-depth look at the recent imaging-genetics investigations of dyslexia. PMID:23916419
Genetic Risk Score Modelling for Disease Progression in New-Onset Type 1 Diabetes Patients
DEFF Research Database (Denmark)
Brorsson, Caroline A; Nielsen, Lotte B; Andersen, Marie-Louise
2016-01-01
Genome-wide association studies (GWAS) have identified over 40 type 1 diabetes risk loci. The clinical impact of these loci on β-cell function during disease progression is unknown. We aimed at testing whether a genetic risk score could predict glycemic control and residual β-cell function in type...... 1 diabetes (T1D). As gene expression may represent an intermediate phenotype between genetic variation and disease, we hypothesized that genes within T1D loci which are expressed in islets and transcriptionally regulated by proinflammatory cytokines would be the best predictors of disease...... constructed a genetic risk score based on the cumulative number of risk alleles carried in children with newly diagnosed T1D. With each additional risk allele carried, HbA1c levels increased significantly within first year after diagnosis. Network and gene ontology (GO) analyses revealed that several...
Risk Assessment and Integration Team (RAIT) Portfolio Risk Analysis Strategy
Edwards, Michelle
2010-01-01
Impact at management level: Qualitative assessment of risk criticality in conjunction with risk consequence, likelihood, and severity enable development of an "investment policy" towards managing a portfolio of risks. Impact at research level: Quantitative risk assessments enable researchers to develop risk mitigation strategies with meaningful risk reduction results. Quantitative assessment approach provides useful risk mitigation information.
Risk Assessment in the 21st Century - Conference Abstract ...
For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response assessment. Originally sound and effective, with increasing dependence on chemical tools and the number of chemicals in commerce, this traditional approach is no longer sufficient. This presentation provides an update on current progress in achieving the goals outlined in the NAS reports: “Toxicology Testing in the 21st Century”, “Exposure Science in the 21st Century”, and most recently, “Using 21st Century Science to Improve Risk-Related Evaluations.” The presentation highlights many of the advances lead by the EPA. Topics covered include the evolution of the mode of action concept into the chemically agnostic, adverse outcome pathway (AOP), a systems-based data framework that facilitates integration of modifiable factors (e.g., genetic variation, life stages), and an understanding of networks, and mixtures. Further, the EDSP pivot is used to illustrate how AOPs drive development of predictive models for risk assessment based on assembly of high throughput assays representing AOP key elements. The birth of computational exposure science, capable of large-scale predictive exposure models, is reviewed. Although still in its infancy, development of non-targeted analysis to begin addressing the exposome is presented, as is the systems-based AEP that integrates exposure, toxicokinetics and AOPs into a comprehensive framework
Barr, Peter B; Silberg, Judy; Dick, Danielle M; Maes, Hermine H
2018-05-14
Childhood socioeconomic status (SES) is an important aspect of early life environment associated with later life health/health behaviors, including alcohol misuse. However, alcohol misuse is modestly heritable and involves differing etiological pathways. Externalizing disorders show significant genetic overlap with substance use, suggesting an impulsivity pathway to alcohol misuse. Alcohol misuse also overlaps with internalizing disorders, suggesting alcohol is used to cope. These differing pathways could lead to different patterns over time and/or differential susceptibility to environmental conditions, such as childhood SES. We examine whether: 1) genetic risk for externalizing and internalizing disorders influence trajectories of alcohol problems across adolescence to adulthood, 2) childhood SES alters genetic risk these disorders on trajectories of alcohol problems, and 3) these patterns are consistent across sex. We find modest evidence of gene-environment interaction. Higher childhood SES increases the risk of alcohol problems in late adolescence/early adulthood, while lower childhood SES increases the risk of alcohol problems in later adulthood, but only among males at greater genetic risk of externalizing disorders. Females from lower SES families with higher genetic risk of internalizing or externalizing disorders have greater risk of developing alcohol problems. Copyright © 2018 Elsevier Ltd. All rights reserved.
Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill
2011-01-01
Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…
Taylor, S
2011-01-01
Community attitudes research regarding genetic issues is important when contemplating the potential value and utilisation of predictive testing for common diseases in mainstream health services. This article aims to report population-based attitudes and discuss their relevance to integrating genetic services in primary health contexts. Men's and women's attitudes were investigated via population-based omnibus telephone survey in Queensland, Australia. Randomly selected adults (n = 1,230) with a mean age of 48.8 years were interviewed regarding perceptions of genetic determinants of health; benefits of genetic testing that predict 'certain' versus 'probable' future illness; and concern, if any, regarding potential misuse of genetic test information. Most (75%) respondents believed genetic factors significantly influenced health status; 85% regarded genetic testing positively although attitudes varied with age. Risk-based information was less valued than certainty-based information, but women valued risk information significantly more highly than men. Respondents reported 'concern' (44%) and 'no concern' (47%) regarding potential misuse of genetic information. This study contributes important population-based data as most research has involved selected individuals closely impacted by genetic disorders. While community attitudes were positive regarding genetic testing, genetic literacy is important to establish. The nature of gender differences regarding risk perception merits further study and has policy and service implications. Community concern about potential genetic discrimination must be addressed if health benefits of testing are to be maximised. Larger questions remain in scientific, policy, service delivery, and professional practice domains before predictive testing for common disorders is efficacious in mainstream health care. Copyright © 2011 S. Karger AG, Basel.
[Risk Assessment and Risk Management of Chemicals in China].
Wang, Tie-yu; Zhou, Yun-qiao; Li, Qi-feng; Lü, Yong-long
2016-02-15
Risk assessment and risk management have been increasingly approved as an effective approach for appropriate disposal and scientific management of chemicals. This study systematically analyzed the risk assessment methods of chemicals from three aspects including health risk, ecological risk and regional risk. Based on the current situation of classification and management towards chemicals in China, a specific framework of risk management on chemicals was proposed by selecting target chemicals, predominant industries and related stakeholders as the objects. The results of the present study will provide scientific support for improving risk assessment and reasonable management of chemicals in China.
2014-01-01
Background Thoroughbred racehorses are subject to non-traumatic distal limb bone fractures that occur during racing and exercise. Susceptibility to fracture may be due to underlying disturbances in bone metabolism which have a genetic cause. Fracture risk has been shown to be heritable in several species but this study is the first genetic analysis of fracture risk in the horse. Results Fracture cases (n = 269) were horses that sustained catastrophic distal limb fractures while racing on UK racecourses, necessitating euthanasia. Control horses (n = 253) were over 4 years of age, were racing during the same time period as the cases, and had no history of fracture at the time the study was carried out. The horses sampled were bred for both flat and National Hunt (NH) jump racing. 43,417 SNPs were employed to perform a genome-wide association analysis and to estimate the proportion of genetic variance attributable to the SNPs on each chromosome using restricted maximum likelihood (REML). Significant genetic variation associated with fracture risk was found on chromosomes 9, 18, 22 and 31. Three SNPs on chromosome 18 (62.05 Mb – 62.15 Mb) and one SNP on chromosome 1 (14.17 Mb) reached genome-wide significance (p fracture than cases, p = 1 × 10-4), while a second haplotype increases fracture risk (cases at 3.39 times higher risk of fracture than controls, p = 0.042). Conclusions Fracture risk in the Thoroughbred horse is a complex condition with an underlying genetic basis. Multiple genomic regions contribute to susceptibility to fracture risk. This suggests there is the potential to develop SNP-based estimators for genetic risk of fracture in the Thoroughbred racehorse, using methods pioneered in livestock genetics such as genomic selection. This information would be useful to racehorse breeders and owners, enabling them to reduce the risk of injury in their horses. PMID:24559379
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...
International Nuclear Information System (INIS)
Jibiri, N.N.; Oguntade, G. T.
2007-01-01
The main source of radiation doses received by humans from man-made sources of ionizing radiation in medicine and industry comes from X-rays. The genetic risks of ionizing radiation effects on an individual who is occupationally exposed largely depend on the magnitude of the radiation dose received, period of practice, work load and radio logical procedures involved. In this work, using the linear non-thresh old model, we have attempted to assess the level of genetic risk of occupationally exposed individuals in two medical and industrial establishments in Nigeria by estimating their genetically significant dose values. The estimation was based on continuous personnel radiation dose monitoring data for the individuals in each of the establishments over a three year period (1998-2001). The estimated genetically significant dose values in the years considered were 12 mSv for the medical, and 29 mSv for the industrial personnel. Appropriate radiation protection precautions should be taken by the personnel to adhere to standard operational practices in order to minimize the genetically significant dose resulting from radio logical practices
Associations between self-referral and health behavior responses to genetic risk information.
Christensen, Kurt D; Roberts, J Scott; Zikmund-Fisher, Brian J; Kardia, Sharon Lr; McBride, Colleen M; Linnenbringer, Erin; Green, Robert C
2015-01-01
Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies. Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer's disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure. Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p change long-term care insurance among SRPs (20% vs 5%, p behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings. ClinicalTrials.gov NCT00089882 and NCT00462917.
Risk Assessment in the 21st Century | Science Inventory | US ...
For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response assessment. Originally sound and effective, with increasing dependence on chemical tools and the number of chemicals in commerce, this traditional approach is no longer adequate. This presentation provides an update on current progress in achieving the goals outlined in the NAS report on Toxicology Testing in the 21st Century, highlighting many of the advances lead by the EPA. Topics covered include the evolution of the mode of action framework into a chemically agnostic, adverse outcome pathway (AOP), a systems-based data framework that facilitates integration of modifiable factors (e.g., genetic variation, life stages), and an understanding of networks, and mixtures. Further, the EDSP pivot is used to illustrate how AOPs drive development of predictive models for risk assessment based on assembly of high throughput assays representing AOP key elements. The birth of computational exposure science, capable of large-scale predictive exposure models, is reviewed. Although still in its infancy, development of non-targeted analysis to begin addressing exposome also is presented. Finally, the systems-based AEP is described that integrates exposure, toxicokinetics and AOPs into a comprehensive framework. For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response as
Genetically modified foods: safety, risks and public concerns-a review.
Bawa, A S; Anilakumar, K R
2013-12-01
Genetic modification is a special set of gene technology that alters the genetic machinery of such living organisms as animals, plants or microorganisms. Combining genes from different organisms is known as recombinant DNA technology and the resulting organism is said to be 'Genetically modified (GM)', 'Genetically engineered' or 'Transgenic'. The principal transgenic crops grown commercially in field are herbicide and insecticide resistant soybeans, corn, cotton and canola. Other crops grown commercially and/or field-tested are sweet potato resistant to a virus that could destroy most of the African harvest, rice with increased iron and vitamins that may alleviate chronic malnutrition in Asian countries and a variety of plants that are able to survive weather extremes. There are bananas that produce human vaccines against infectious diseases such as hepatitis B, fish that mature more quickly, fruit and nut trees that yield years earlier and plants that produce new plastics with unique properties. Technologies for genetically modifying foods offer dramatic promise for meeting some areas of greatest challenge for the 21st century. Like all new technologies, they also pose some risks, both known and unknown. Controversies and public concern surrounding GM foods and crops commonly focus on human and environmental safety, labelling and consumer choice, intellectual property rights, ethics, food security, poverty reduction and environmental conservation. With this new technology on gene manipulation what are the risks of "tampering with Mother Nature"?, what effects will this have on the environment?, what are the health concerns that consumers should be aware of? and is recombinant technology really beneficial? This review will also address some major concerns about the safety, environmental and ecological risks and health hazards involved with GM foods and recombinant technology.
International Nuclear Information System (INIS)
Buhl, T.E.; Hansen, W.R.
1984-05-01
Estimators for calculating the risk of cancer and genetic disorders induced by exposure to ionizing radiation have been recommended by the US National Academy of Sciences Committee on the Biological Effects of Ionizing Radiations, the UN Scientific Committee on the Effects of Atomic Radiation, and the International Committee on Radiological Protection. These groups have also considered the risks of somatic effects other than cancer. The US National Council on Radiation Protection and Measurements has discussed risk estimate procedures for radiation-induced health effects. The recommendations of these national and international advisory committees are summarized and compared in this report. Based on this review, two procedures for risk estimation are presented for use in radiological assessments performed by the US Department of Energy under the National Environmental Policy Act of 1969 (NEPA). In the first procedure, age- and sex-averaged risk estimators calculated with US average demographic statistics would be used with estimates of radiation dose to calculate the projected risk of cancer and genetic disorders that would result from the operation being reviewed under NEPA. If more site-specific risk estimators are needed, and the demographic information is available, a second procedure is described that would involve direct calculation of the risk estimators using recommended risk-rate factors. The computer program REPCAL has been written to perform this calculation and is described in this report. 25 references, 16 tables
Energy Technology Data Exchange (ETDEWEB)
Buhl, T.E.; Hansen, W.R.
1984-05-01
Estimators for calculating the risk of cancer and genetic disorders induced by exposure to ionizing radiation have been recommended by the US National Academy of Sciences Committee on the Biological Effects of Ionizing Radiations, the UN Scientific Committee on the Effects of Atomic Radiation, and the International Committee on Radiological Protection. These groups have also considered the risks of somatic effects other than cancer. The US National Council on Radiation Protection and Measurements has discussed risk estimate procedures for radiation-induced health effects. The recommendations of these national and international advisory committees are summarized and compared in this report. Based on this review, two procedures for risk estimation are presented for use in radiological assessments performed by the US Department of Energy under the National Environmental Policy Act of 1969 (NEPA). In the first procedure, age- and sex-averaged risk estimators calculated with US average demographic statistics would be used with estimates of radiation dose to calculate the projected risk of cancer and genetic disorders that would result from the operation being reviewed under NEPA. If more site-specific risk estimators are needed, and the demographic information is available, a second procedure is described that would involve direct calculation of the risk estimators using recommended risk-rate factors. The computer program REPCAL has been written to perform this calculation and is described in this report. 25 references, 16 tables.
Genetic variants influencing circulating lipid levels and risk of coronary artery disease
D. Waterworth (Dawn); S.L. Ricketts (Sally); K. Song (Kijoung); L. Chen (Leslie); J.H. Zhao (Jing Hua); S. Ripatti (Samuli); Y.S. Aulchenko (Yurii); W. Zhang (Weihua); X. Yuan (Xin); N. Lim (Noha); J. Luan; S. Ashford (Sofie); E. Wheeler (Eleanor); E.H. Young (Elizabeth); D. Hadley (David); J.R. Thompson (John); P.S. Braund (Peter); T. Johnson (Toby); M.V. Struchalin (Maksim); I. Surakka (Ida); R.N. Luben (Robert); K-T. Khaw (Kay-Tee); S.A. Rodwell (Sheila); R.J.F. Loos (Ruth); S.M. Boekholdt (Matthijs); M. Inouye (Michael); P. Deloukas (Panagiotis); P. Elliott (Paul); D. Schlessinger; S. Sanna (Serena); A. Scuteri (Angelo); A.U. Jackson (Anne); K.L. Mohlke (Karen); J. Tuomilehto (Jaakko); R. Roberts (Robert); A. Stewart (Alison); Y.A. Kesaniemi (Antero); R. Mahley (Robert); S.M. Grundy (Scott); W.L. McArdle (Wendy); L. Cardon (Lon); G. Waeber (Gérard); P. Vollenweider (Peter); J.C. Chambers (John); M. Boehnke (Michael); G.R. Abecasis (Gonçalo); V. Salomaa (Veikko); M.R. Järvelin; A. Ruokonen (Aimo); I.E. Barroso (Inês); S.E. Epstein (Stephen); H. Hakonarson (Hakon); D.J. Rader (Daniel); M.P. Reilly (Muredach); J.C.M. Witteman (Jacqueline); A.S. Hall (Alistair); N.J. Samani (Nilesh); D.P. Strachan (David); P. Barter (Phil); P. Tikka-Kleemola (Päivi); J.S. Kooner (Jaspal); L. Peltonen (Leena Johanna); N.J. Wareham (Nick); R. McPherson (Ruth); V. Mooser (Vincent); M.S. Sandhu (Manjinder)
2010-01-01
textabstractOBJECTIVE-: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density
Genetic Variants Influencing Circulating Lipid Levels and Risk of Coronary Artery Disease
Waterworth, Dawn M.; Ricketts, Sally L.; Song, Kijoung; Chen, Li; Zhao, Jing Hua; Ripatti, Samuli; Aulchenko, Yurii S.; Zhang, Weihua; Yuan, Xin; Lim, Noha; Luan, Jian'an; Ashford, Sofie; Wheeler, Eleanor; Young, Elizabeth H.; Hadley, David; Thompson, John R.; Braund, Peter S.; Johnson, Toby; Struchalin, Maksim; Surakka, Ida; Luben, Robert; Khaw, Kay-Tee; Rodwell, Sheila A.; Loos, Ruth J. F.; Boekholdt, S. Matthijs; Inouye, Michael; Deloukas, Panagiotis; Elliott, Paul; Schlessinger, David; Sanna, Serena; Scuteri, Angelo; Jackson, Anne; Mohlke, Karen L.; Tuomilehto, Jaako; Roberts, Robert; Stewart, Alexandre; Kesäniemi, Y. Antero; Mahley, Robert W.; Grundy, Scott M.; McArdle, Wendy; Cardon, Lon; Waeber, Gérard; Vollenweider, Peter; Chambers, John C.; Boehnke, Michael; Abecasis, Gonçalo R.; Salomaa, Veikko; Järvelin, Marjo-Riitta; Ruokonen, Aimo; Barroso, Inês; Epstein, Stephen E.; Hakonarson, Hakon H.; Rader, Daniel J.; Reilly, Muredach P.; Witteman, Jacqueline C. M.; Hall, Alistair S.; Samani, Nilesh J.; Strachan, David P.; Barter, Philip; van Duijn, Cornelia M.; Kooner, Jaspal S.; Peltonen, Leena; Wareham, Nicholas J.; McPherson, Ruth; Mooser, Vincent; Sandhu, Manjinder S.
2010-01-01
Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
Patient caries risk assessment
DEFF Research Database (Denmark)
Twetman, Svante; Fontana, Margherita
2009-01-01
Risk assessment is an essential component in the decision-making process for the correct prevention and management of dental caries. Multiple risk factors and indicators have been proposed as targets in the assessment of risk of future disease, varying sometimes based on the age group at which...... they are targeted. Multiple reviews and systematic reviews are available in the literature on this topic. This chapter focusses primarily on results of reviews based on longitudinal studies required to establish the accuracy of caries risk assessment. These findings demonstrate that there is a strong body...... of evidence to support that caries experience is still, unfortunately, the single best predictor for future caries development. In young children, prediction models which include a variety of risk factors seem to increase the accuracy of the prediction, while the usefulness of additional risk factors...
Summary of the BEIR V committee's estimates of genetic risks
International Nuclear Information System (INIS)
Grahn, D.
1990-01-01
The Committee on the Biological Effects of Ionizing Radiations (BEIR V) was constituted in late 1986 to conduct a comprehensive review of the biological effects of ionizing radiations focusing on information reported since the conclusion of the 1980 BEIR study, and to provide new estimates of the risks of genetic and somatic effects in humans due to low-level exposures of ionizing radiation. The Committee preferred the doubling-dose method of genetic risk estimation over the direct method. Data from animal (mouse) studies provide a median value of 100 to 114 cGy for long-term low dose rate exposure doubling doses. These values are lower than the median from human studies. The BEIR Committee believed that a doubling dose of 100 cGy would be a prudent value leading to conservative estimates. The estimated risks themselves are not much different from those generated by previous BEIR committees, UNSCEAR, and other published estimates. The Committee estimates that between 100 and 200 added cases per million live births will be observed at genetic equilibrium if the population is exposed each generation to a dose of 0.01 Sv (1 rem). Nearly half ware attributed to clinically mild dominant defects, and the balance to congenital abnormalities. (L.L.) (2 tabs.)
Lee, Min-Young; Ku, Bo Mi; Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se-Hoon; Park, Keunchil; Oh, Young Lyun; Hong, Mineui; Jeong, Han-Sin; Son, Young-Ik; Baek, Chung-Hwan; Ahn, Myung-Ju
2017-10-01
Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.
Directory of Open Access Journals (Sweden)
Andrew Mark Mcintosh
2012-07-01
Full Text Available Hyperpolarization-activated cyclic nucleotide-gated (HCN channels are encoded by four genes (HCN1-4 and, through activation by cyclic AMP (cAMP, represent a point of convergence for several psychosis risk genes. On the basis of positive preliminary data, we sought to test whether genetic variation in HCN1-4 conferred risk of depression or cognitive impairment in the Generation Scotland: Scottish Family Health Study. HCN1, HCN2, HCN3 and HCN4 were genotyped for 43 haplotype-tagging SNPs and tested for association with DSM-IV depression, neuroticism and a battery of cognitive tests assessing cognitive ability, memory, verbal fluency and psychomotor performance. No association was found between any HCN channel gene SNP and risk of depression, neuroticism or on any cognitive measure. The current study does not support a genetic role for HCN channels in conferring risk of depression or cognitive impairment in human subjects within the Scottish population.
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.
Risk Assessment Stability: A Revalidation Study of the Arizona Risk/Needs Assessment Instrument
Schwalbe, Craig S.
2009-01-01
The actuarial method is the gold standard for risk assessment in child welfare, juvenile justice, and criminal justice. It produces risk classifications that are highly predictive and that may be robust to sampling error. This article reports a revalidation study of the Arizona Risk/Needs Assessment instrument, an actuarial instrument for juvenile…
Genetic association of the KLK4 locus with risk of prostate cancer.
Directory of Open Access Journals (Sweden)
Felicity Lose
Full Text Available The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (± 10 kb in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥ 7 revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the P(trend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r(2 ≥ 0.98. Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.
International Nuclear Information System (INIS)
Gjorgiev, Blaže; Kančev, Duško; Čepin, Marko
2012-01-01
Highlights: ► Multi-objective optimization of STI based on risk-informed decision making. ► Four different genetic algorithms (GAs) techniques are used as optimization tool. ► Advantages/disadvantages among the four different GAs applied are emphasized. - Abstract: The risk-informed decision making (RIDM) process, where insights gained from the probabilistic safety assessment are contemplated together with other engineering insights, is gaining an ever-increasing attention in the process industries. Increasing safety systems availability by applying RIDM is one of the prime goals for the authorities operating with nuclear power plants. Additionally, equipment ageing is gradually becoming a major concern in the process industries and especially in the nuclear industry, since more and more safety-related components are approaching or are already in their wear-out phase. A significant difficulty regarding the consideration of ageing effects on equipment (un)availability is the immense uncertainty the available equipment ageing data are associated to. This paper presents an approach for safety system unavailability reduction by optimizing the related test and maintenance schedule suggested by the technical specifications in the nuclear industry. Given the RIDM philosophy, two additional insights, i.e. ageing data uncertainty and test and maintenance costs, are considered along with unavailability insights gained from the probabilistic safety assessment for a selected standard safety system. In that sense, an approach for multi-objective optimization of the equipment surveillance test interval is proposed herein. Three different objective functions related to each one of the three different insights discussed above comprise the multi-objective nature of the optimization process. Genetic algorithm technique is utilized as an optimization tool. Four different types of genetic algorithms are utilized and consequently comparative analysis is conducted given the
A genetic assessment of the English bulldog
Pedersen, Niels C.; Pooch, Ashley S.; Liu, Hongwei
2016-01-01
Background This study examines genetic diversity among 102 registered English Bulldogs used for breeding based on maternal and paternal haplotypes, allele frequencies in 33 highly polymorphic short tandem repeat (STR) loci on 25 chromosomes, STR-linked dog leukocyte antigen (DLA) class I and II haplotypes, and the number and size of genome-wide runs of homozygosity (ROH) determined from high density SNP arrays. The objective was to assess whether the breed retains enough genetic diversity to ...
Genetic effects of low-level irradiation
International Nuclear Information System (INIS)
Selby, P.B.
1980-01-01
Recent estimates of the genetic effects of radiation by two widely recognized committees (BEIR III and UNSCEAR 1977) are based to a large extent on data collected in mice using either the specific-locus method or the approach of empirically determining the nature and extent of radiation-induced genetic damage to the skeleton. Both committees made use of doubling-dose and direct methods of estimating genetic hazard. Their estimates can be applied to assessments of risk resulting from medical irradiation in terms both of risk to the population at large and to the individual
Genetic Testing for Type 2 Diabetes in High-Risk Children: the Case for Primordial Prevention
Directory of Open Access Journals (Sweden)
Jennifer Wessel
2017-09-01
Full Text Available Extensive research now demonstrates that lifestyle modification can significantly lower risk of developing type 2 diabetes (T2D in high-risk adults. In children, the evidence for lifestyle modification is not as robust, but the rapidly rising rate of obesity in children coupled with the substantial difficulty in changing behaviors later in life illuminates the need to implement prevention efforts early in the life course of children. Genetic data can now be used early in the life course to identify children at high-risk of developing T2D before traditional clinical measures can detect the presence of prediabetes; a metabolic condition associated with obesity that significantly increases risk for developing T2D. Such early detection of risk may enable the promotion of “primordial prevention” in which parents implement behavior change for their at risk children. Young children with genetic risk are a novel target population. Here we review the literature on genetic testing for prevention as it relates to chronic diseases and specifically use T2D as a model. We discuss the history of primordial prevention, the need for primordial prevention of T2D and the role genetic testing has in primordial prevention of high-risk families.
Assessment of the safety of foods derived from genetically modified (GM) crops.
König, A; Cockburn, A; Crevel, R W R; Debruyne, E; Grafstroem, R; Hammerling, U; Kimber, I; Knudsen, I; Kuiper, H A; Peijnenburg, A A C M; Penninks, A H; Poulsen, M; Schauzu, M; Wal, J M
2004-07-01
This paper provides guidance on how to assess the safety of foods derived from genetically modified crops (GM crops); it summarises conclusions and recommendations of Working Group 1 of the ENTRANSFOOD project. The paper provides an approach for adapting the test strategy to the characteristics of the modified crop and the introduced trait, and assessing potential unintended effects from the genetic modification. The proposed approach to safety assessment starts with the comparison of the new GM crop with a traditional counterpart that is generally accepted as safe based on a history of human food use (the concept of substantial equivalence). This case-focused approach ensures that foods derived from GM crops that have passed this extensive test-regime are as safe and nutritious as currently consumed plant-derived foods. The approach is suitable for current and future GM crops with more complex modifications. First, the paper reviews test methods developed for the risk assessment of chemicals, including food additives and pesticides, discussing which of these methods are suitable for the assessment of recombinant proteins and whole foods. Second, the paper presents a systematic approach to combine test methods for the safety assessment of foods derived from a specific GM crop. Third, the paper provides an overview on developments in this area that may prove of use in the safety assessment of GM crops, and recommendations for research priorities. It is concluded that the combination of existing test methods provides a sound test-regime to assess the safety of GM crops. Advances in our understanding of molecular biology, biochemistry, and nutrition may in future allow further improvement of test methods that will over time render the safety assessment of foods even more effective and informative. Copryright 2004 Elsevier Ltd.
Directory of Open Access Journals (Sweden)
Roman Corral
Full Text Available Cigarette smoking, high alcohol intake, and low dietary folate levels are risk factors for colorectal adenomas. Oxidative damage caused by these three factors can be repaired through the base excision repair pathway (BER. We hypothesized that genetic variation in BER might modify colorectal adenoma risk. In a sigmoidoscopy-based study, we examined associations between 182 haplotype tagging SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential role as modifiers of the effect cigarette smoking, alcohol intake, and dietary folate levels. Among all individuals, no statistically significant associations between BER SNPs and adenoma risk persisted after correction for multiple comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1 and one in NTHL1, and among African-Americans one SNP in APEX1 that were associated with colorectal adenoma risk. Significant associations were also observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013; FEN1 interaction p = 0.013, one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024 and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08 on colorectal adenoma risk. These findings support a role for genetic variants in the BER pathway as potential modifiers of colorectal adenoma risk. Our findings strengthen the role of oxidative damage induced by key lifestyle and dietary risk factors in colorectal adenoma formation.
Assessment of Multifactor Gene-Environment Interactions and Ovarian Cancer Risk
DEFF Research Database (Denmark)
Usset, Joseph L; Raghavan, Rama; Tyrer, Jonathan P
2016-01-01
and non-obese women. METHODS: We considered interactions between 11,441 SNPs within 80 candidate genes related to hormone biosynthesis and metabolism and insulin-like growth factors with six hormone-related factors (oral contraceptive use, parity, endometriosis, tubal ligation, hormone replacement therapy...... Future work is needed to develop powerful statistical methods able to detect these complex interactions. IMPACT: Assessment of multifactor interaction is feasible, and, here, suggests that the relationship between genetic variants within candidate genes and hormone-related risk factors may vary EOC...
Jensen, Majken K; Bartz, Traci M; Djoussé, Luc; Kizer, Jorge R; Zieman, Susan J; Rimm, Eric B; Siscovick, David S; Psaty, Bruce M; Ix, Joachim H; Mukamal, Kenneth J
2013-10-01
Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes. Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992-1993. Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (Pfasting glucose concentrations (1.9 mg/dL [95% CI, 1.2-2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (-0.3 mg/dL [95% CI, -1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P=0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant. Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal.
Eleven loci with new reproducible genetic associations with allergic disease risk
Ferreira, Manuel A.R.; Vonk, Judith M; Baurecht, Hansjörg; Marenholz, Ingo; Tian, Chao; Hoffman, Joshua D; Helmer, Quinta; Tillander, Annika; Ullemar, Vilhelmina; Lu, Yi; Rüschendorf, Franz; Hinds, David A; Hübner, Norbert; Weidinger, Stephan; Magnusson, Patrik Ke; Jorgenson, Eric; Lee, Young-Ae; Boomsma, Dorret I; Karlsson, Robert; Almqvist, Catarina; Koppelman, Gerard H; Paternoster, Lavinia
2018-01-01
BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.
Energy Technology Data Exchange (ETDEWEB)
Duster, T.
1998-11-01
The proliferation of genetic screening and testing is requiring increasing numbers of Americans to integrate genetic knowledge and interventions into their family life and personal experience. This study examines the social processes that occur as families at risk for two of the most common autosomal recessive diseases, sickle cell disease (SC) and cystic fibrosis (CF), encounter genetic testing. Each of these diseases is found primarily in a different ethnic/racial group (CF in Americans of North European descent and SC in Americans of West African descent). This has permitted them to have a certain additional lens on the role of culture in integrating genetic testing into family life and reproductive planning. A third type of genetic disorder, the thalassemias was added to the sample in order to extent the comparative frame and to include other ethnic and racial groups.
RISK MANAGEMENT: AN INTEGRATED APPROACH TO RISK MANAGEMENT AND ASSESSMENT
Directory of Open Access Journals (Sweden)
Szabo Alina
2012-12-01
Full Text Available Purpose: The objective of this paper is to offer an overview over risk management cycle by focusing on prioritization and treatment, in order to ensure an integrated approach to risk management and assessment, and establish the ‘top 8-12’ risks report within the organization. The interface with Internal Audit is ensured by the implementation of the scoring method to prioritize risks collected from previous generated risk report. Methodology/approach: Using evidence from other research in the area and the professional expertise, this article outlines an integrated approach to risk assessment and risk management reporting processes, by separating the risk in two main categories: strategic and operational risks. The focus is on risk prioritization and scoring; the final output will comprise a mix of strategic and operational (‘top 8-12’ risks, which should be used to establish the annual Internal Audit plan. Originality/value: By using an integrated approach to risk assessment and risk management will eliminate the need for a separate Internal Audit risk assessment over prevailing risks. It will reduce the level of risk assessment overlap by different functions (Tax, Treasury, Information System over the same risk categories as a single methodology, is used and will align timings of risk assessment exercises. The risk prioritization by usage of risk and control scoring criteria highlights the combination between financial and non-financial impact criteria allowing risks that do not naturally lend themselves to a financial amount to be also assessed consistently. It is emphasized the usage of score method to prioritize the risks included in the annual audit plan in order to increase accuracy and timelines.
Polygenic Risk, Rapid Childhood Growth, and the Development of Obesity
Belsky, Daniel W.; Moffitt, Terrie E.; Houts, Renate; Bennett, Gary G.; Biddle, Andrea K.; Blumenthal, James A.; Evans, James P.; Harrington, HonaLee; Sugden, Karen; Williams, Benjamin; Poulton, Richie; Caspi, Avshalom
2012-01-01
Objective To test how genomic loci identified in genome-wide association studies influence the development of obesity. Design A 38-year prospective longitudinal study of a representative birth cohort. Setting The Dunedin Multidisciplinary Health and Development Study, Dunedin, New Zealand. Participants One thousand thirty-seven male and female study members. Main Exposures We assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in genome-wide association studies of obesity-related phenotypes. We assessed family history from parent body mass index data collected when study members were 11 years of age. Main Outcome Measures Body mass index growth curves, developmental phenotypes of obesity, and adult obesity outcomes were defined from anthropometric assessments at birth and at 12 subsequent in-person interviews through 38 years of age. Results Individuals with higher genetic risk scores were more likely to be chronically obese in adulthood. Genetic risk first manifested as rapid growth during early childhood. Genetic risk was unrelated to birth weight. After birth, children at higher genetic risk gained weight more rapidly and reached adiposity rebound earlier and at a higher body mass index. In turn, these developmental phenotypes predicted adult obesity, mediating about half the genetic effect on adult obesity risk. Genetic associations with growth and obesity risk were independent of family history, indicating that the genetic risk score could provide novel information to clinicians. Conclusions Genetic variation linked with obesity risk operates, in part, through accelerating growth in the early childhood years after birth. Etiological research and prevention strategies should target early childhood to address the obesity epidemic. PMID:22665028
Assessing genetically modified crops to minimize the risk of increased food allergy: a review.
Goodman, Richard E; Hefle, Susan L; Taylor, Steven L; van Ree, Ronald
2005-06-01
The first genetically modified (GM) crops approved for food use (tomato and soybean) were evaluated for safety by the United States Food and Drug Administration prior to commercial production. Among other factors, those products and all additional GM crops that have been grown commercially have been evaluated for potential increases in allergenic properties using methods that are consistent with the current understanding of food allergens and knowledge regarding the prediction of allergenic activity. Although there have been refinements, the key aspects of the evaluation have not changed. The allergenic properties of the gene donor and the host (recipient) organisms are considered in determining the appropriate testing strategy. The amino acid sequence of the encoded protein is compared to all known allergens to determine whether the protein is a known allergen or is sufficiently similar to any known allergen to indicate an increased probability of allergic cross-reactivity. Stability of the protein in the presence of acid with the stomach protease pepsin is tested as a risk factor for food allergenicity. In vitro or in vivo human IgE binding are tested when appropriate, if the gene donor is an allergen or the sequence of the protein is similar to an allergen. Serum donors and skin test subjects are selected based on their proven allergic responses to the gene donor or to material containing the allergen that was matched in sequence. While some scientists and regulators have suggested using animal models, performing broadly targeted serum IgE testing or extensive pre- or post-market clinical tests, current evidence does not support these tests as being predictive or practical. Based on the evidence to date, the current assessment process has worked well to prevent the unintended introduction of allergens in commercial GM crops.
The association of XRCC3 Thr241Met genetic variant with risk of ...
African Journals Online (AJOL)
genetic variant could be potentially associated with the risk of prostate cancer. However ... Results: Overall, significant associations were detected in the heterozygote comparison genetic model. (CT versus (vs.) ..... Quantifying hetero- geneity in ...
Investigating Married Adults' Communal Coping with Genetic Health Risk and Perceived Discrimination
Smith, Rachel A.; Sillars, Alan; Chesnut, Ryan P.; Zhu, Xun
2017-01-01
Increased genetic testing in personalized medicine presents unique challenges for couples, including managing disease risk and potential discrimination as a couple. This study investigated couples' conflicts and support gaps as they coped with perceived genetic discrimination. We also explored the degree to which communal coping was beneficial in reducing support gaps, and ultimately stress. Dyadic analysis of married adults (N = 266, 133 couples), in which one person had the genetic risk for serious illness, showed that perceived discrimination predicted more frequent conflicts about AATD-related treatment, privacy boundaries, and finances, which, in turn, predicted wider gaps in emotion and esteem support, and greater stress for both spouses. Communal coping predicted lower support gaps for both partners and marginally lower stress. PMID:29731540
Investigating Married Adults' Communal Coping with Genetic Health Risk and Perceived Discrimination.
Smith, Rachel A; Sillars, Alan; Chesnut, Ryan P; Zhu, Xun
2018-01-01
Increased genetic testing in personalized medicine presents unique challenges for couples, including managing disease risk and potential discrimination as a couple. This study investigated couples' conflicts and support gaps as they coped with perceived genetic discrimination. We also explored the degree to which communal coping was beneficial in reducing support gaps, and ultimately stress. Dyadic analysis of married adults ( N = 266, 133 couples), in which one person had the genetic risk for serious illness, showed that perceived discrimination predicted more frequent conflicts about AATD-related treatment, privacy boundaries, and finances, which, in turn, predicted wider gaps in emotion and esteem support, and greater stress for both spouses. Communal coping predicted lower support gaps for both partners and marginally lower stress.
Gorin, Michael B.
2012-01-01
Age-related macular degeneration (AMD) is a common condition among the elderly population that leads to the progressive central vision loss and serious compromise of quality of life for its sufferers. It is also one of the few disorders for whom the investigation of its genetics has yielded rich insights into its diversity and causality and holds the promise of enabling clinicians to provide better risk assessments for individuals as well as to develop and selectively deploy new therapeutics to either prevent or slow the development of disease and lessen the threat of vision loss. The genetics of AMD began initially with the appreciation of familial aggregation and increase risk and expanded with the initial association of APOE variants with the disease. The first major breakthroughs came with family-based linkage studies of affected (and discordant) sibs, which identified a number of genetic loci and led to the targeted search of the 1q31 and 10q26 loci for associated variants. Three of the initial four reports for the CFH variant, Y402H, were based on regional candidate searches, as were the two initial reports of the ARMS2/HTRA1 locus variants. Case-control association studies initially also played a role in discovering the major genetic variants for AMD, and the success of those early studies have been used to fuel enthusiasm for the methodology for a number of diseases. Until 2010, all of the subsequent genetic variants associated with AMD came from candidate gene testing based on the complement factor pathway. In 2010, several large-scale genome-wide association studies (GWAS) identified genes that had not been previously identified. Much of this historical information is available in a number of recent reviews.(Chen et al., 2010b; Deangelis et al., 2011; Fafowora and Gorin, 2012b; Francis and Klein, 2011; Kokotas et al., 2011) Large meta analysis of AMD GWAS has added new loci and variants to this collection.(Chen et al., 2010a; Kopplin et al., 2010; Yu et
Kuiper, Harry A; Kok, Esther J; Davies, Howard V
2013-09-01
This commentary focuses on the potential added value of and need for (sub)-chronic testing of whole genetically modified (GM) foods in rodents to assess their safety. Such routine testing should not be required since, due to apparent weaknesses in the approach, it does not add to current risk assessment of GM foods. Moreover, the demand for routine testing using animals is in conflict with the European Union (EU) Commission's efforts to reduce animal experimentation. Regulating agencies in the EU are invited to respect the sound scientific principles applied to the risk assessment of foods derived from GM plants and not to interfere in the risk assessment by introducing extra requirements based on pseudo-scientific or political considerations. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.
The evolving genetic risk for sporadic ALS.
Gibson, Summer B; Downie, Jonathan M; Tsetsou, Spyridoula; Feusier, Julie E; Figueroa, Karla P; Bromberg, Mark B; Jorde, Lynn B; Pulst, Stefan M
2017-07-18
To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates. © 2017 American Academy of Neurology.
Risk assessment: 'A consumer's perspective'
International Nuclear Information System (INIS)
Waterhouse, Rachel
1992-01-01
The paper assesses the concept of risk, risk assessment and tolerability of risk from consumer point of view. Review of existing UK and EC directives on certain products and appliances is also covered
Risk assessment: 'A consumer's perspective'
Energy Technology Data Exchange (ETDEWEB)
Waterhouse, Rachel [Consumer' s Association, Health and Safety Commission (United Kingdom)
1992-07-01
The paper assesses the concept of risk, risk assessment and tolerability of risk from consumer point of view. Review of existing UK and EC directives on certain products and appliances is also covered.
Safety assessment of genetically modified foods
Kleter, G.A.; Noordam, M.Y.
2016-01-01
The cultivation of genetically modified (GM) crops has steadily increased since their introduction to the market in the mid-1990s. Before these crops can be grown and sold they have to obtain regulatory approval in many countries, the process of which includes a pre-market safety assessment. The
Lobular breast cancer: incidence and genetic and non-genetic risk factors.
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.
Gene panel testing for inherited cancer risk.
Hall, Michael J; Forman, Andrea D; Pilarski, Robert; Wiesner, Georgia; Giri, Veda N
2014-09-01
Next-generation sequencing technologies have ushered in the capability to assess multiple genes in parallel for genetic alterations that may contribute to inherited risk for cancers in families. Thus, gene panel testing is now an option in the setting of genetic counseling and testing for cancer risk. This article describes the many gene panel testing options clinically available to assess inherited cancer susceptibility, the potential advantages and challenges associated with various types of panels, clinical scenarios in which gene panels may be particularly useful in cancer risk assessment, and testing and counseling considerations. Given the potential issues for patients and their families, gene panel testing for inherited cancer risk is recommended to be offered in conjunction or consultation with an experienced cancer genetic specialist, such as a certified genetic counselor or geneticist, as an integral part of the testing process. Copyright © 2014 by the National Comprehensive Cancer Network.
Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.
Directory of Open Access Journals (Sweden)
Paul J Leo
2017-08-01
Full Text Available A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4% of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
Genetic variability in Sudanese Acacia senegal (L.) assessed by ...
African Journals Online (AJOL)
TUOYO
2010-07-26
Jul 26, 2010 ... Full Length Research Paper. Genetic variability in Sudanese Acacia senegal (L.) assessed by random amplified polymorphic DNA. Rami S. Habeballa*, Nada B. Hamza and Eisa I. El Gaali. Commission for Biotechnology and Genetic Engineering, National Centre for Research, Khartoum, Sudan. P. O. Box.
Kendler, Kenneth S; Myers, John; Prescott, Carol A
2007-11-01
Although genetic risk factors have been found to contribute to dependence on both licit and illicit psychoactive substances, we know little of how these risk factors interrelate. To clarify the structure of genetic and environmental risk factors for symptoms of dependence on cannabis, cocaine, alcohol, caffeine, and nicotine in males and females. Lifetime history by structured clinical interview. General community. Four thousand eight hundred sixty-five members of male-male and female-female pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measure Lifetime symptoms of abuse of and dependence on cannabis, cocaine, alcohol, caffeine, and nicotine. Controlling for greater symptom prevalence in males, genetic and environmental parameters could be equated across sexes. Two models explained the data well. The best-fit exploratory model contained 2 genetic factors and 1 individual environmental factor contributing to all substances. The first genetic factor loaded strongly on cocaine and cannabis dependence; the second, on alcohol and nicotine dependence. Nicotine and caffeine had high substance-specific genetic effects. A confirmatory model, which also fit well, contained 1 illicit drug genetic factor--loading only on cannabis and cocaine--and 1 licit drug genetic factor loading on alcohol, caffeine, and nicotine. However, these factors were highly intercorrelated (r = + 0.82). Large substance-specific genetic effects remained for nicotine and caffeine. The pattern of genetic and environmental risk factors for psychoactive substance dependence was similar in males and females. Genetic risk factors for dependence on common psychoactive substances cannot be explained by a single factor. Rather, 2 genetic factors-one predisposing largely to illicit drug dependence, the other primarily to licit drug dependence-are needed. Furthermore, a large proportion of the genetic influences on nicotine and particularly caffeine dependence
Using risk assessment in periodontics.
Woodman, Alan J
2014-08-01
Risk assessment has become a regular feature in both dental practice and society as a whole, and principles used to assess risk in society are similar to those used in a clinical setting. Although the concept of risk assessment as a prognostic indicator for periodontal disease incidence and activity is well established in the management of periodontitis, the use of risk assessment to manage the practical treatment of periodontitis and its sequelae appears to have less foundation. A simple system of initial risk assessment - building on the use of the Basic Periodontal Examination (BPE), clinical, medical and social factors - is described, linked to protocols for delivering care suited to general dental practice and stressing the role of long-term supportive care. The risks of not treating the patient are considered, together with the possible causes of failure, and the problems of successful treatment are illustrated by the practical management of post-treatment recession.
Birth Characteristics and Childhood Leukemia Risk: Correlations With Genetic Markers.
Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, Mehmet F; Scheurer, Michael E; Dorak, Mehmet T
2015-07-01
Birth characteristics such as birth order, birth weight, birth defects, and Down syndrome showed some of the first risk associations with childhood leukemia. Examinations of correlations between birth characteristics and leukemia risk markers have been limited to birth weight-related genetic polymorphisms. We integrated information on nongenetic and genetic markers by evaluating the relationship of birth characteristics, genetic markers for childhood acute lymphoblastic leukemia (ALL) susceptibility, and ALL risk together. The multiethnic study consisted of cases with childhood ALL (n=161) and healthy controls (n=261). Birth characteristic data were collected through questionnaires, and genotyping was achieved by TaqMan SNP Genotyping Assays. We observed risk associations for birth weight over 4000 g (odds ratios [OR]=1.93; 95% confidence interval [CI], 1.16-3.19), birth length (OR=1.18 per inch; 95% CI, 1.01-1.38), and with gestational age (OR=1.10 per week; 95% CI, 1.00-1.21). Only the HFE tag single-nucleotide polymorphism (SNP) rs9366637 showed an inverse correlation with a birth characteristic, gestational age, with a gene-dosage effect (P=0.005), and in interaction with a transferrin receptor rs3817672 genotype (Pinteraction=0.05). This correlation translated into a strong association for rs9366637 with preterm birth (OR=5.0; 95% CI, 1.19-20.9). Our study provides evidence for the involvement of prenatal events in the development of childhood ALL. The inverse correlation of rs9366637 with gestational age has implications on the design of HFE association studies in birth weight and childhood conditions using full-term newborns as controls.
A total risk assessment methodology for security assessment
International Nuclear Information System (INIS)
Auilar, Richard; Pless, Daniel J.; Kaplan, Paul Garry; Silva, Consuelo Juanita; Rhea, Ronald Edward; Wyss, Gregory Dane; Conrad, Stephen Hamilton
2009-01-01
Sandia National Laboratories performed a two-year Laboratory Directed Research and Development project to develop a new collaborative risk assessment method to enable decision makers to fully consider the interrelationships between threat, vulnerability, and consequence. A five-step Total Risk Assessment Methodology was developed to enable interdisciplinary collaborative risk assessment by experts from these disciplines. The objective of this process is promote effective risk management by enabling analysts to identify scenarios that are simultaneously achievable by an adversary, desirable to the adversary, and of concern to the system owner or to society. The basic steps are risk identification, collaborative scenario refinement and evaluation, scenario cohort identification and risk ranking, threat chain mitigation analysis, and residual risk assessment. The method is highly iterative, especially with regard to scenario refinement and evaluation. The Total Risk Assessment Methodology includes objective consideration of relative attack likelihood instead of subjective expert judgment. The 'probability of attack' is not computed, but the relative likelihood for each scenario is assessed through identifying and analyzing scenario cohort groups, which are groups of scenarios with comparable qualities to the scenario being analyzed at both this and other targets. Scenarios for the target under consideration and other targets are placed into cohort groups under an established ranking process that reflects the following three factors: known targeting, achievable consequences, and the resources required for an adversary to have a high likelihood of success. The development of these target cohort groups implements, mathematically, the idea that adversaries are actively choosing among possible attack scenarios and avoiding scenarios that would be significantly suboptimal to their objectives. An adversary who can choose among only a few comparable targets and scenarios (a
A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk
2017-10-01
AWARD NUMBER: W81XWH-15-1-0529 TITLE: A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk PRINCIPAL INVESTIGATOR...AND SUBTITLE A Model for Understanding the Genetic Basis for Disparity in Prostate Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1...STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer is the most commonly diagnosed cancer in
Supporting Risk Assessment: Accounting for Indirect Risk to Ecosystem Components.
Directory of Open Access Journals (Sweden)
Cathryn Clarke Murray
Full Text Available The multi-scalar complexity of social-ecological systems makes it challenging to quantify impacts from human activities on ecosystems, inspiring risk-based approaches to assessments of potential effects of human activities on valued ecosystem components. Risk assessments do not commonly include the risk from indirect effects as mediated via habitat and prey. In this case study from British Columbia, Canada, we illustrate how such "indirect risks" can be incorporated into risk assessments for seventeen ecosystem components. We ask whether (i the addition of indirect risk changes the at-risk ranking of the seventeen ecosystem components and if (ii risk scores correlate with trophic prey and habitat linkages in the food web. Even with conservative assumptions about the transfer of impacts or risks from prey species and habitats, the addition of indirect risks in the cumulative risk score changes the ranking of priorities for management. In particular, resident orca, Steller sea lion, and Pacific herring all increase in relative risk, more closely aligning these species with their "at-risk status" designations. Risk assessments are not a replacement for impact assessments, but-by considering the potential for indirect risks as we demonstrate here-they offer a crucial complementary perspective for the management of ecosystems and the organisms within.
Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk
DEFF Research Database (Denmark)
Rudolph, Anja; Hein, Rebecca; Lindström, Sara
2013-01-01
Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...
Germline genetic variants in the Wnt/beta-catenin pathway as predictors of colorectal cancer risk
Hildebrandt, Michelle A.T.; Reyes, Monica E.; Lin, Moubin; He, Yonggang; Nguyen, Son V.; Hawk, Ernest T.; Wu, Xifeng
2016-01-01
Background The Wnt/beta-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. Methods We assessed 172 variants in 26 genes from the Wnt/beta-catenin pathway in 809 CRC cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. Results Eighteen SNPs in the pathway were significantly associated with CRC risk (P <0.05) in the discovery phase. We observed a significant dose-response increase in CRC risk by number of risk genotypes carried (P = 4.19 × 10−8). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for CRC risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk with a pooled OR of 0.85 (95% CI: 0.76–0.94, P = 0.001). Although borderline significant in the replication population, APC:rs2545162 was highly significant in the pooled analysis - OR: 1.42, 95% CI: 1.16–1.74, P =0.00085. Functional assessment identified several potential biological mechanisms underlying these associations. Conclusions Our findings suggest that common germline variants in the Wnt/beta-catenin pathway maybe involved in CRC development. Impact These variants may be informative in CRC risk assessment to identify individuals at increased risk who would be candidates for screening. PMID:26809274
Multiobjective genetic algorithm approaches to project scheduling under risk
Kılıç, Murat; Kilic, Murat
2003-01-01
In this thesis, project scheduling under risk is chosen as the topic of research. Project scheduling under risk is defined as a biobjective decision problem and is formulated as a 0-1 integer mathematical programming model. In this biobjective formulation, one of the objectives is taken as the expected makespan minimization and the other is taken as the expected cost minimization. As the solution approach to this biobjective formulation genetic algorithm (GA) is chosen. After carefully invest...
24 CFR 35.315 - Risk assessment.
2010-04-01
... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Risk assessment. 35.315 Section 35... Provided by a Federal Agency Other Than HUD § 35.315 Risk assessment. Each owner shall complete a risk assessment in accordance with 40 CFR 745.227(d). Each risk assessment shall be completed in accordance with...
Pasick, Rena J; Joseph, Galen; Stewart, Susan; Kaplan, Celia; Lee, Robin; Luce, Judith; Davis, Sharon; Marquez, Titas; Nguyen, Tung; Guerra, Claudia
2016-10-01
To determine the effectiveness of a statewide telephone service in identifying low-income women at risk for hereditary breast and ovarian cancer and referring them to free genetic counseling. From June 2010 through August 2011, eligible callers to California's toll-free breast and cervical cancer telephone service were screened for their family histories of breast and ovarian cancer. High-risk women were identified and called for a baseline survey and randomization to an immediate offer of genetic counseling or a mailed brochure on how to obtain counseling. Clinic records were used to assess receipt of genetic counseling after 2 months. Among 1212 eligible callers, 709 (58.5%) agreed to answer family history questions; 102 (14%) were at high risk (25% Hispanic, 46% White, 10% Black, 16% Asian, 3% of other racial/ethnic backgrounds). Of the high-risk women offered an immediate appointment, 39% received counseling during the intervention period, as compared with 4.5% of those receiving the brochure. A public health approach to the rare but serious risk of hereditary breast and ovarian cancer can be successful when integrated into the efforts of existing safety net organizations.
Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.
Lubitz, Steven A; Lunetta, Kathryn L; Lin, Honghuang; Arking, Dan E; Trompet, Stella; Li, Guo; Krijthe, Bouwe P; Chasman, Daniel I; Barnard, John; Kleber, Marcus E; Dörr, Marcus; Ozaki, Kouichi; Smith, Albert V; Müller-Nurasyid, Martina; Walter, Stefan; Agarwal, Sunil K; Bis, Joshua C; Brody, Jennifer A; Chen, Lin Y; Everett, Brendan M; Ford, Ian; Franco, Oscar H; Harris, Tamara B; Hofman, Albert; Kääb, Stefan; Mahida, Saagar; Kathiresan, Sekar; Kubo, Michiaki; Launer, Lenore J; MacFarlane, Peter W; Magnani, Jared W; McKnight, Barbara; McManus, David D; Peters, Annette; Psaty, Bruce M; Rose, Lynda M; Rotter, Jerome I; Silbernagel, Guenther; Smith, Jonathan D; Sotoodehnia, Nona; Stott, David J; Taylor, Kent D; Tomaschitz, Andreas; Tsunoda, Tatsuhiko; Uitterlinden, Andre G; Van Wagoner, David R; Völker, Uwe; Völzke, Henry; Murabito, Joanne M; Sinner, Moritz F; Gudnason, Vilmundur; Felix, Stephan B; März, Winfried; Chung, Mina; Albert, Christine M; Stricker, Bruno H; Tanaka, Toshihiro; Heckbert, Susan R; Jukema, J Wouter; Alonso, Alvaro; Benjamin, Emelia J; Ellinor, Patrick T
2014-04-01
This study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. We performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). We observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. The chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Slob, Wout; Bakker, Martine I; Biesebeek, Jan Dirk Te; Bokkers, Bas G H
2014-08-01
Current methods for cancer risk assessment result in single values, without any quantitative information on the uncertainties in these values. Therefore, single risk values could easily be overinterpreted. In this study, we discuss a full probabilistic cancer risk assessment approach in which all the generally recognized uncertainties in both exposure and hazard assessment are quantitatively characterized and probabilistically evaluated, resulting in a confidence interval for the final risk estimate. The methodology is applied to three example chemicals (aflatoxin, N-nitrosodimethylamine, and methyleugenol). These examples illustrate that the uncertainty in a cancer risk estimate may be huge, making single value estimates of cancer risk meaningless. Further, a risk based on linear extrapolation tends to be lower than the upper 95% confidence limit of a probabilistic risk estimate, and in that sense it is not conservative. Our conceptual analysis showed that there are two possible basic approaches for cancer risk assessment, depending on the interpretation of the dose-incidence data measured in animals. However, it remains unclear which of the two interpretations is the more adequate one, adding an additional uncertainty to the already huge confidence intervals for cancer risk estimates. © 2014 Society for Risk Analysis.
Supporting Risk Assessment: Accounting for Indirect Risk to Ecosystem Components
Mach, Megan E.; Martone, Rebecca G.; Singh, Gerald G.; O, Miriam; Chan, Kai M. A.
2016-01-01
The multi-scalar complexity of social-ecological systems makes it challenging to quantify impacts from human activities on ecosystems, inspiring risk-based approaches to assessments of potential effects of human activities on valued ecosystem components. Risk assessments do not commonly include the risk from indirect effects as mediated via habitat and prey. In this case study from British Columbia, Canada, we illustrate how such “indirect risks” can be incorporated into risk assessments for seventeen ecosystem components. We ask whether (i) the addition of indirect risk changes the at-risk ranking of the seventeen ecosystem components and if (ii) risk scores correlate with trophic prey and habitat linkages in the food web. Even with conservative assumptions about the transfer of impacts or risks from prey species and habitats, the addition of indirect risks in the cumulative risk score changes the ranking of priorities for management. In particular, resident orca, Steller sea lion, and Pacific herring all increase in relative risk, more closely aligning these species with their “at-risk status” designations. Risk assessments are not a replacement for impact assessments, but—by considering the potential for indirect risks as we demonstrate here—they offer a crucial complementary perspective for the management of ecosystems and the organisms within. PMID:27632287
Avalanche risk assessment in Russia
Komarov, Anton; Seliverstov, Yury; Sokratov, Sergey; Glazovskaya, Tatiana; Turchaniniva, Alla
2017-04-01
The avalanche prone area covers about 3 million square kilometers or 18% of total area of Russia and pose a significant problem in most mountain regions of the country. The constant growth of economic activity, especially in the North Caucasus region and therefore the increased avalanche hazard lead to the demand of the large-scale avalanche risk assessment methods development. Such methods are needed for the determination of appropriate avalanche protection measures as well as for economic assessments during all stages of spatial planning of the territory. The requirement of natural hazard risk assessments is determined by the Federal Law of Russian Federation. However, Russian Guidelines (SP 11-103-97; SP 47.13330.2012) are not clearly presented concerning avalanche risk assessment calculations. A great size of Russia territory, vast diversity of natural conditions and large variations in type and level of economic development of different regions cause significant variations in avalanche risk values. At the first stage of research the small scale avalanche risk assessment was performed in order to identify the most common patterns of risk situations and to calculate full social risk and individual risk. The full social avalanche risk for the territory of country was estimated at 91 victims. The area of territory with individual risk values lesser then 1×10(-6) covers more than 92 % of mountain areas of the country. Within these territories the safety of population can be achieved mainly by organizational activities. Approximately 7% of mountain areas have 1×10(-6) - 1×10(-4) individual risk values and require specific mitigation measures to protect people and infrastructure. Territories with individual risk values 1×10(-4) and above covers about 0,1 % of the territory and include the most severe and hazardous mountain areas. The whole specter of mitigation measures is required in order to minimize risk. The future development of such areas is not recommended
Risk assessment in international operations
International Nuclear Information System (INIS)
Stricklin, Daniela L.
2008-01-01
During international peace-keeping missions, a diverse number of non-battle hazards may be encountered, which range from heavily polluted areas, endemic disease, toxic industrial materials, local violence, traffic, and even psychological factors. Hence, elevated risk levels from a variety of sources are encountered during deployments. With the emphasis within the Swedish military moving from national defense towards prioritization of international missions in atypical environments, the risk of health consequences, including long term health effects, has received greater consideration. The Swedish military is interested in designing an optimal approach for assessment of health threats during deployments. The Medical Intelligence group at FOI CBRN Security and Defence in Umea has, on request from and in collaboration with the Swedish Armed Forces, reviewed a variety of international health threat and risk assessment models for military operations. Application of risk assessment methods used in different phases of military operations will be reviewed. An overview of different international approaches used in operational risk management (ORM) will be presented as well as a discussion of the specific needs and constraints for health risk assessment in military operations. This work highlights the specific challenges of risk assessment that are unique to the deployment setting such as the assessment of exposures to a variety of diverse hazards concurrently
Implications of probabilistic risk assessment
International Nuclear Information System (INIS)
Cullingford, M.C.; Shah, S.M.; Gittus, J.H.
1987-01-01
Probabilistic risk assessment (PRA) is an analytical process that quantifies the likelihoods, consequences and associated uncertainties of the potential outcomes of postulated events. Starting with planned or normal operation, probabilistic risk assessment covers a wide range of potential accidents and considers the whole plant and the interactions of systems and human actions. Probabilistic risk assessment can be applied in safety decisions in design, licensing and operation of industrial facilities, particularly nuclear power plants. The proceedings include a review of PRA procedures, methods and technical issues in treating uncertainties, operating and licensing issues and future trends. Risk assessment for specific reactor types or components and specific risks (eg aircraft crashing onto a reactor) are used to illustrate the points raised. All 52 articles are indexed separately. (U.K.)
Goldstein, Bernard; Carruth, Russellyn S
2004-04-01
Risk analysis has been recognized and validated in World Trade Organization (WTO) decision processes. In recent years the precautionary principle has been proposed as an additional or alternative approach to standard risk assessment. The precautionary principle has also been advocated by some who see it as part of postmodern democracy in which more power is given to the public on health and safety matters relative to the judgments of technocrats. A more cynical view is that the precautionary principle is particularly championed by the European Community as a means to erect trade barriers. The WTO ruling against the European Community's trade barrier against beef from hormone-treated cattle seemed to support the use of risk assessment and appeared to reject the argument that the precautionary principle was a legitimate basis for trade barriers. However, a more recent WTO decision on asbestos contains language suggesting that the precautionary principle, in the form of taking into account public perception, may be acceptable as a basis for a trade barrier. This decision, if followed in future WTO trade disputes, such as for genetically modified foods, raises many issues central to the field of risk analysis. It is too early to tell whether the precautionary principle will become accepted in WTO decisions, either as a supplement or a substitute for standard risk assessment. But it would undermine the value of the precautionary principle if this principle were misused to justify unwarranted trade barriers.
Uncertainties in risk assessment at USDOE facilities
Energy Technology Data Exchange (ETDEWEB)
Hamilton, L.D.; Holtzman, S.; Meinhold, A.F.; Morris, S.C.; Rowe, M.D.
1994-01-01
The United States Department of Energy (USDOE) has embarked on an ambitious program to remediate environmental contamination at its facilities. Decisions concerning cleanup goals, choices among cleanup technologies, and funding prioritization should be largely risk-based. Risk assessments will be used more extensively by the USDOE in the future. USDOE needs to develop and refine risk assessment methods and fund research to reduce major sources of uncertainty in risk assessments at USDOE facilities. The terms{open_quote} risk assessment{close_quote} and{open_quote} risk management{close_quote} are frequently confused. The National Research Council (1983) and the United States Environmental Protection Agency (USEPA, 1991a) described risk assessment as a scientific process that contributes to risk management. Risk assessment is the process of collecting, analyzing and integrating data and information to identify hazards, assess exposures and dose responses, and characterize risks. Risk characterization must include a clear presentation of {open_quotes}... the most significant data and uncertainties...{close_quotes} in an assessment. Significant data and uncertainties are {open_quotes}...those that define and explain the main risk conclusions{close_quotes}. Risk management integrates risk assessment information with other considerations, such as risk perceptions, socioeconomic and political factors, and statutes, to make and justify decisions. Risk assessments, as scientific processes, should be made independently of the other aspects of risk management (USEPA, 1991a), but current methods for assessing health risks are based on conservative regulatory principles, causing unnecessary public concern and misallocation of funds for remediation.
Uncertainties in risk assessment at USDOE facilities
International Nuclear Information System (INIS)
Hamilton, L.D.; Holtzman, S.; Meinhold, A.F.; Morris, S.C.; Rowe, M.D.
1994-01-01
The United States Department of Energy (USDOE) has embarked on an ambitious program to remediate environmental contamination at its facilities. Decisions concerning cleanup goals, choices among cleanup technologies, and funding prioritization should be largely risk-based. Risk assessments will be used more extensively by the USDOE in the future. USDOE needs to develop and refine risk assessment methods and fund research to reduce major sources of uncertainty in risk assessments at USDOE facilities. The terms open-quote risk assessment close-quote and open-quote risk management close-quote are frequently confused. The National Research Council (1983) and the United States Environmental Protection Agency (USEPA, 1991a) described risk assessment as a scientific process that contributes to risk management. Risk assessment is the process of collecting, analyzing and integrating data and information to identify hazards, assess exposures and dose responses, and characterize risks. Risk characterization must include a clear presentation of open-quotes... the most significant data and uncertainties...close quotes in an assessment. Significant data and uncertainties are open-quotes...those that define and explain the main risk conclusionsclose quotes. Risk management integrates risk assessment information with other considerations, such as risk perceptions, socioeconomic and political factors, and statutes, to make and justify decisions. Risk assessments, as scientific processes, should be made independently of the other aspects of risk management (USEPA, 1991a), but current methods for assessing health risks are based on conservative regulatory principles, causing unnecessary public concern and misallocation of funds for remediation
Advanced Test Reactor outage risk assessment
International Nuclear Information System (INIS)
Thatcher, T.A.; Atkinson, S.A.
1997-01-01
Beginning in 1997, risk assessment was performed for each Advanced Test Reactor (ATR) outage aiding the coordination of plant configuration and work activities (maintenance, construction projects, etc.) to minimize the risk of reactor fuel damage and to improve defense-in-depth. The risk assessment activities move beyond simply meeting Technical Safety Requirements to increase the awareness of risk sensitive configurations, to focus increased attention on the higher risk activities, and to seek cost-effective design or operational changes that reduce risk. A detailed probabilistic risk assessment (PRA) had been performed to assess the risk of fuel damage during shutdown operations including heavy load handling. This resulted in several design changes to improve safety; however, evaluation of individual outages had not been performed previously and many risk insights were not being utilized in outage planning. The shutdown PRA provided the necessary framework for assessing relative and absolute risk levels and assessing defense-in-depth. Guidelines were written identifying combinations of equipment outages to avoid. Screening criteria were developed for the selection of work activities to receive review. Tabulation of inherent and work-related initiating events and their relative risk level versus plant mode has aided identification of the risk level the scheduled work involves. Preoutage reviews are conducted and post-outage risk assessment is documented to summarize the positive and negative aspects of the outage with regard to risk. The risk for the outage is compared to the risk level that would result from optimal scheduling of the work to be performed and to baseline or average past performance
Maskrey, Andrew; Safaie, Sahar
2015-04-01
Disaster risk management strategies, policies and actions need to be based on evidence of current disaster loss and risk patterns, past trends and future projections, and underlying risk factors. Faced with competing demands for resources, at any level it is only possible to priorities a range of disaster risk management strategies and investments with adequate understanding of realised losses, current and future risk levels and impacts on economic growth and social wellbeing as well as cost and impact of the strategy. The mapping and understanding of the global risk landscape has been greatly enhanced by the latest iteration of the GAR Global Risk Assessment and the objective of this submission is to present the GAR global risk assessment which contributed to Global Assessment Report (GAR) 2015. This initiative which has been led by UNISDR, was conducted by a consortium of technical institutions from around the world and has covered earthquake, cyclone, riverine flood, and tsunami probabilistic risk for all countries of the world. In addition, the risks associated with volcanic ash in the Asia-Pacific region, drought in various countries in sub-Saharan Africa and climate change in a number of countries have been calculated. The presentation will share thee results as well as the experience including the challenges faced in technical elements as well as the process and recommendations for the future of such endeavour.
Deterministic quantitative risk assessment development
Energy Technology Data Exchange (ETDEWEB)
Dawson, Jane; Colquhoun, Iain [PII Pipeline Solutions Business of GE Oil and Gas, Cramlington Northumberland (United Kingdom)
2009-07-01
Current risk assessment practice in pipeline integrity management is to use a semi-quantitative index-based or model based methodology. This approach has been found to be very flexible and provide useful results for identifying high risk areas and for prioritizing physical integrity assessments. However, as pipeline operators progressively adopt an operating strategy of continual risk reduction with a view to minimizing total expenditures within safety, environmental, and reliability constraints, the need for quantitative assessments of risk levels is becoming evident. Whereas reliability based quantitative risk assessments can be and are routinely carried out on a site-specific basis, they require significant amounts of quantitative data for the results to be meaningful. This need for detailed and reliable data tends to make these methods unwieldy for system-wide risk k assessment applications. This paper describes methods for estimating risk quantitatively through the calibration of semi-quantitative estimates to failure rates for peer pipeline systems. The methods involve the analysis of the failure rate distribution, and techniques for mapping the rate to the distribution of likelihoods available from currently available semi-quantitative programs. By applying point value probabilities to the failure rates, deterministic quantitative risk assessment (QRA) provides greater rigor and objectivity than can usually be achieved through the implementation of semi-quantitative risk assessment results. The method permits a fully quantitative approach or a mixture of QRA and semi-QRA to suit the operator's data availability and quality, and analysis needs. For example, consequence analysis can be quantitative or can address qualitative ranges for consequence categories. Likewise, failure likelihoods can be output as classical probabilities or as expected failure frequencies as required. (author)
Genetic susceptibility loci, pesticide exposure and prostate cancer risk.
Directory of Open Access Journals (Sweden)
Stella Koutros
Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.
Evaluation of thermal risk assessment
International Nuclear Information System (INIS)
Loos, J.J.; Perry, E.S.
1993-01-01
Risk assessment was done in 1983 to estimate the ecological hazard of increasing the generating load and thermal output of an electric generating station. Subsequently, long-term monitoring in the vicinity of the station allowed verification of the predictions made in the risk assessment. This presentation will review the efficacy of early risk assessment methods in producing useful predictions from a resource management point of view. In 1984, the Chalk Point Generating facility of the Potomac Electric Power Company increased it's median generating load by 100%. Prior to this operational change, the Academy of Natural Sciences of Philadelphia synthesized site specific data, model predictions, and results from literature to assess the risk of additional waste heat to the Patuxent River subestuary of Chesapeake Bay. Risk was expressed as the number of days per year that various species of fish and the blue crab would be expected to avoid the discharge vicinity. Accuracy of these predictions is assessed by comparing observed fish and crab distributions and their observed frequencies of avoidance to those predicted. It is concluded that the predictions of this early risk assessment were sufficiently accurate to produce a reliable resource management decision
Mutuality and solidarity: assessing risks and sharing losses.
Wilkie, D
1997-01-01
Mutuality is the principle of private, commercial insurance; individuals enter the pool for sharing losses, and pay according to the best estimate of the risk they bring with them. Solidarity is the sharing of losses with payment according to some other scheme; this is the principle of state social insurance; essential features of solidarity are comprehensiveness and compulsion. Private insurance is subject to the uberrima fides principle, or utmost good faith; each side declares all it knows about the risk. The Disability Discrimination Act requires insurers to justify disability discrimination on the basis of relevant information, acturial, statistical or medical, on which it is reasonable to rely. It could be very damaging to private insurance to abandon uberrima fides. However, although some genetic information is clearly useful to underwriters, other information may be so general as to be of little use. The way in which mortality rates are assessed is also explained. PMID:9304668
On risk assessment of energy production
International Nuclear Information System (INIS)
Kunii, Katsuhiko
2005-07-01
Today we cannot ignore the risk of health and/or environment by energy production such as power generation since the risk has been made large enough. In this report an information survey has been done in order to know the outline and points of risk assessment. Based on the information of reports and literature about risk assessment, have been surveyed mainly the external cost assessment of power generation (in which quantification of health and/or environment risk has been done), in addition, risks of disasters, accidents, investments, finance etc. and impacts of those risks on social activities. The remarks obtained by the survey are as follows: 1) Some of external cost assessment of power generation show different results even if the assessment conditions of technology, site, etc. are mostly the same. It is necessary to remark on the information such as basic data, model, background, application limit of assessment considering the reliability. 2) Especially it is considered that the reliability of risk assessment is not enough at present because of the lack of basic data. (author)
Henneman, L.; Timmermans, D. R.; Bouwman, C. M.; Cornel, M. C.; Meijers-Heijboer, H.
2011-01-01
Population breast cancer screening programs by mammography are offered to women based on age. It has been suggested that a screening program based on genetic risk profile could be more effective by targeting interventions at those at higher genetic risk. This study explores women's attitudes towards
The importance of radiation risk assessment
International Nuclear Information System (INIS)
Pochin, E.E.
1979-01-01
In its Publication 26, ICRP recommends a system of radiation dose limitation that is designed to ensure adequate protection from the harmful effects of radiation in conditions both of occupational and of environmental exposure. Clearly, however, no such system can be recommended or accepted as sufficiently safe unless the risks of the resultant exposures have been quantitatively assessed. Publication 26 reflects the increasing quantitative information that is now available on (a) carcinogenic risks of radiation in man, both from exposure of the whole body and from that of individual organs, at moderate exposures; (b) theoretical bases for inference of risk, from moderate to lower exposures; (c) genetic risks in the mouse, and inferences from such risks to those in man; (d) the dose equivalent levels at which certain non-stochastic effects may be induced. Despite a number of uncertainties, substantially improved estimates can therefore be made of the levels of safety that are likely to be achieved by observing the Commission's recommended dose limits, and the associated system of limitation of exposures to levels as low as reasonably achievable below these limits. Both for occupational exposure and for the exposure of the members of the public, these estimates are expressed in Publication 26 in terms of the risk of inducing fatal malignancies or serious hereditary ill health. These frequencies are compared with those of occupational fatalities in other industries or with accidental fatalities amongst the general public. The comparison between harm from radiation and from other agents in different industries is extended in ICRP-27 (on ''Problems Involved in Developing an Index of Harm'') in a review of the time lost through occupational diseases and non-fatal accidents, as well as from fatal diseases and accidents, so that the levels of safety achievable by the Commission's recommendations can be reviewed in the general perspective of occupational safety. (author)
Hershberger, Patricia E.; Gallo, Agatha M.; Kavanaugh, Karen; Olshansky, Ellen; Schwartz, Alan; Tur-Kaspa, Ilan
2012-01-01
Exponential growth in genomics has led to public and private initiatives worldwide that have dramatically increased the number of procreative couples who are aware of their ability to transmit genetic disorders to their future children. Understanding how couples process the meaning of being genetically at risk for their procreative life lags far behind the advances in genomic and reproductive sciences. Moreover, society, policy makers, and clinicians are not aware of the experiences and nuances involved when modern couples are faced with using Preimplantation Genetic Diagnosis (PGD). The purpose of this study was to discover the decision-making process of genetically at-risk couples as they decide whether to use PGD to prevent the transmission of known single-gene or sex-linked genetic disorders to their children. A qualitative, grounded theory design guided the study in which 22 couples (44 individual partners) from the USA, who were actively considering PGD, participated. Couples were recruited from June 2009 to May 2010 from the Internet and from a large PGD center and a patient newsletter. In-depth semi-structured interviews were completed with each individual partner within the couple dyad, separate from their respective partner. We discovered that couples move through four phases (Identify, Contemplate, Resolve, Engage) of a complex, dynamic, and iterative decision-making process where multiple, sequential decisions are made. In the Identify phase, couples acknowledge the meaning of their at-risk status. Parenthood and reproductive options are explored in the Contemplate phase, where 41% of couples remained for up to 36 months before moving into the Resolve phase. In Resolve, one of three decisions about PGD use is reached, including: Accepting, Declining, or Oscillating. Actualizing decisions occur in the Engage phase. Awareness of the decision-making process among genetically at-risk couples provides foundational work for understanding critical processes
Defense Programs Transportation Risk Assessment
International Nuclear Information System (INIS)
Clauss, D.B.
1994-01-01
This paper provides an overview of the methodology used in a probabilistic transportation risk assessment conducted to assess the probabilities and consequences of inadvertent dispersal of radioactive materials arising from severe transportation accidents. The model was developed for the Defense Program Transportation Risk Assessment (DPTRA) study. The analysis incorporates several enhancements relative to previous risk assessments of hazardous materials transportation including newly-developed statistics on the frequencies and severities of tractor semitrailer accidents and detailed route characterization using the 1990 Census data
Reichborn-Kjennerud, T; Krueger, R F; Ystrom, E; Torvik, F A; Rosenström, T H; Aggen, S H; South, S C; Neale, M C; Knudsen, G P; Kendler, K S; Czajkowski, N O
2017-09-01
DSM-5 includes two conceptualizations of personality disorders (PDs). The classification in Section II is identical to the one found in DSM-IV, and includes 10 categorical PDs. The Alternative Model (Section III) includes criteria for dimensional measures of maladaptive personality traits organized into five domains. The degree to which the two conceptualizations reflect the same etiological factors is not known. We use data from a large population-based sample of adult twins from the Norwegian Institute of Public Health Twin Panel on interview-based DSM-IV PDs and a short self-report inventory that indexes the five domains of the DSM-5 Alternative Model plus a domain explicitly targeting compulsivity. Schizotypal, Paranoid, Antisocial, Borderline, Avoidant, and Obsessive-compulsive PDs were assessed at the same time as the maladaptive personality traits and 10 years previously. Schizoid, Histrionic, Narcissistic, and Dependent PDs were only assessed at the first interview. Biometric models were used to estimate overlap in genetic and environmental risk factors. When measured concurrently, there was 100% genetic overlap between the maladaptive trait domains and Paranoid, Schizotypal, Antisocial, Borderline, and Avoidant PDs. For OCPD, 43% of the genetic variance was shared with the domains. Genetic correlations between the individual domains and PDs ranged from +0.21 to +0.91. The pathological personality trait domains, which are part of the Alternative Model for classification of PDs in DSM-5 Section III, appears to tap, at an aggregate level, the same genetic risk factors as the DSM-5 Section II classification for most of the PDs.
Risk Factor Assessment Branch (RFAB)
The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.
Genetic variants in IL-6/JAK/STAT3 pathway and the risk of CRC.
Wang, Shuwei; Zhang, Weidong
2016-05-01
Interleukin (IL)-6 and the downstream Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway have previously been reported to be important in the development of colorectal cancer (CRC), and several studies have shown the relationship between the polymorphisms of related genes in this pathway with the risk of CRC. However, the findings of these related studies are inconsistent. Moreover, there has no systematic review and meta-analysis to evaluate the relationship between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility. Hence, we conducted a meta-analysis to explore the relationship between polymorphisms in IL-6/JAK/STAT3 pathway genes and CRC risk. Eighteen eligible studies with a total of 13,795 CRC cases and 18,043 controls were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library databases for the period up to September 15, 2015. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to calculate the strength of the association. Our results indicated that IL-6 genetic variants in allele additive model (OR = 1.05, 95 % CI = 1.00, 1.09) and JAK2 genetic variants (OR = 1.40, 95 % CI = 1.15, 1.65) in genotype recessive model were significantly associated with CRC risk. Moreover, the pooled data revealed that IL-6 rs1800795 polymorphism significantly increased the risk of CRC in allele additive model in Europe (OR = 1.07, 95 % CI = 1.01, 1.14). In conclusion, the present findings indicate that IL-6 and JAK2 genetic variants are associated with the increased risk of CRC while STAT3 genetic variants not. We need more well-designed clinical studies covering more countries and population to definitively establish the association between genetic variants in IL-6/JAK/STAT3 pathway and CRC susceptibility.
Mega, J L; Stitziel, N O; Smith, J G; Chasman, D I; Caulfield, M; Devlin, J J; Nordio, F; Hyde, C; Cannon, C P; Sacks, F; Poulter, N; Sever, P; Ridker, P M; Braunwald, E; Melander, O; Kathiresan, S; Sabatine, M S
2015-06-06
Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, pgenetic risk category was 1·72 (1·55-1·92, pgenetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high
Benign breast diseases. Radiology, pathology, risk assessment. 2. ed.
International Nuclear Information System (INIS)
Chinyama, Catherine N.
2014-01-01
Radiological and pathological correlation of the full range of benign breast lesions, with emphasis on screen-detected lesions. Detailed discussion of risk assessment. Revised and updated edition, with a new chapter on gynaecomastia. Ideal aid to the management of patients with benign or indeterminate breast lesions in a multidisciplinary setting. The second edition of this book has been extensively revised and updated. There have been numerous scientific advances in the radiology, pathology and risk assessment of benign breast lesions since the publication of the first edition. The first edition concentrated on screen-detected lesions, which has since been rectified; new symptomatic and screen-detected lesions are discussed in the second edition and include: mastitis and breast abscesses, idiopathic granulomatous mastitis, diabetic mastopathy, phyllodes tumours, gynaecomastia and pseudoangiomatous stromal hyperplasia. The chapters on columnar cell lesions and mucocele-like lesions have been extensively updated. Where applicable, genetic analysis of the benign lesions, which is becoming part of personalised medicine in the field of breast cancer, has been included. The book also presents detailed analyses of the main models, such as the Gail Model, used to assess the subsequent risk of breast cancer in individuals. The current trend in the management of all cancers is preventative. Screening mammography detects early curable cancers as well as indeterminate lesions, the latter of which are invariably pathologically benign. The author has collated important benign lesions and, based on peer-reviewed publications, has documented the relative risk of subsequent cancer to allow the patient and the clinician to implement preventative measures where possible. This book will therefore serve as an essential component of multidisciplinary management of patients with symptomatic and screen-detected benign breast lesions.
Benign breast diseases. Radiology, pathology, risk assessment. 2. ed.
Energy Technology Data Exchange (ETDEWEB)
Chinyama, Catherine N. [Princess Elizabeth Hospital, Le Vauquiedor, St. Martin' s Guernsey, Channel Islands (United Kingdom); Brighton and Sussex Medical School, Brighton (United Kingdom)
2014-04-01
Radiological and pathological correlation of the full range of benign breast lesions, with emphasis on screen-detected lesions. Detailed discussion of risk assessment. Revised and updated edition, with a new chapter on gynaecomastia. Ideal aid to the management of patients with benign or indeterminate breast lesions in a multidisciplinary setting. The second edition of this book has been extensively revised and updated. There have been numerous scientific advances in the radiology, pathology and risk assessment of benign breast lesions since the publication of the first edition. The first edition concentrated on screen-detected lesions, which has since been rectified; new symptomatic and screen-detected lesions are discussed in the second edition and include: mastitis and breast abscesses, idiopathic granulomatous mastitis, diabetic mastopathy, phyllodes tumours, gynaecomastia and pseudoangiomatous stromal hyperplasia. The chapters on columnar cell lesions and mucocele-like lesions have been extensively updated. Where applicable, genetic analysis of the benign lesions, which is becoming part of personalised medicine in the field of breast cancer, has been included. The book also presents detailed analyses of the main models, such as the Gail Model, used to assess the subsequent risk of breast cancer in individuals. The current trend in the management of all cancers is preventative. Screening mammography detects early curable cancers as well as indeterminate lesions, the latter of which are invariably pathologically benign. The author has collated important benign lesions and, based on peer-reviewed publications, has documented the relative risk of subsequent cancer to allow the patient and the clinician to implement preventative measures where possible. This book will therefore serve as an essential component of multidisciplinary management of patients with symptomatic and screen-detected benign breast lesions.
Risk assessments ensure safer power
Energy Technology Data Exchange (ETDEWEB)
1982-02-19
A growth industry is emerging devoted to the study and comparison of the economic, social and health risks posed by large industrial installations. Electricity generation is one area coming under particularly close scrutiny. Types of risk, ways of assessing risk and the difference between experts' analyses and the public perception of risk are given. An example of improved risk assessment helping to reduce deaths and injuries in coal mining is included.
Skin cancer concerns and genetic risk information-seeking in primary care.
Hay, J; Kaphingst, K A; Baser, R; Li, Y; Hensley-Alford, S; McBride, C M
2012-01-01
Genomic testing for common genetic variants associated with skin cancer risk could enable personalized risk feedback to motivate skin cancer screening and sun protection. In a cross-sectional study, we investigated whether skin cancer cognitions and behavioral factors, sociodemographics, family factors, and health information-seeking were related to perceived importance of learning about how (a) genes and (b) health habits affect personal health risks using classification and regression trees (CART). The sample (n = 1,772) was collected in a large health maintenance organization as part of the Multiplex Initiative, ranged in age from 25-40, was 53% female, 41% Caucasian, and 59% African-American. Most reported that they placed somewhat to very high importance on learning about how genes (79%) and health habits (88%) affect their health risks. Social influence actors were associated with information-seeking about genes and health habits. Awareness of family history was associated with importance of health habit, but not genetic, information-seeking. The investment of family and friends in health promotion may be a primary motivator for prioritizing information-seeking about how genes and health habits affect personal health risks and may contribute to the personal value, or personal utility, of risk information. Individuals who seek such risk information may be receptive to interventions aimed to maximize the social implications of healthy lifestyle change to reduce their health risks. Copyright © 2011 S. Karger AG, Basel.
Hardiman, Jill M.; Breyta, Rachel B.; Haskell, Craig A.; Ostberg, Carl O.; Hatten, James R.; Connolly, Patrick J.
2017-09-12
The Upper Columbia United Tribes (UCUT; Spokane, Colville, Kootenai, Coeur d’Alene, and Kalispel Tribes) and Washington Department of Fish and Wildlife want to reintroduce anadromous salmonids to their historical range to restore ecosystem function and lost cultural and spiritual relationships in the upper Columbia River, northeastern Washington. The UCUT contracted with the U.S. Geological Survey to assess risks to resident taxa (existing fish populations in the reintroduction area upstream of Chief Joseph and Grand Coulee Dams) and reintroduced salmon associated with reintroduction. We developed a risk assessment framework for reintroduction of anadromous salmonids upstream of Chief Joseph and Grand Coulee Dams. To accomplish this goal, we applied strategies identified in previous risk assessment frameworks for reintroduction. The risk assessment is an initial step towards an anadromous reintroduction strategy. An initial list of potential donor sources for reintroduction species was developed from previous published sources for Chinook Salmon (Oncorhynchus tshawytscha) donors in the Transboundary Reach of the Columbia River, British Columbia; an ecological risk assessment of upper Columbia River hatchery programs on non-target taxa of concern; and a review of existing hatchery programsDuring two workshops, we further identified and ranked potential donor sources of anadromous Redband Trout (steelhead; O. mykiss), Chinook Salmon, Sockeye Salmon (O. nerka), and Coho Salmon (O. kisutch). We also identified resident fish populations of interest and their primary habitat, location, status, and pathogen concerns to determine the potential risks of reintroduction. Species were deemed of interest based on resource management and potential interactions (that is, genetics, competition, and predation) with introduced species. We developed tables of potential donors by species and characterized potential sources (hatchery and natural origins), populations (individual runs
Prediction of breast cancer risk based on profiling with common genetic variants
DEFF Research Database (Denmark)
Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki
2015-01-01
BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. M...
Prediction of breast cancer risk based on profiling with common genetic variants
N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Lisa); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (Guillermo); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)
2015-01-01
textabstractBackground: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is
Epigenomic strategies at the interface of genetic and environmental risk factors for autism.
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.
Convergent synaptic and circuit substrates underlying autism genetic risks.
McGee, Aaron; Li, Guohui; Lu, Zhongming; Qiu, Shenfeng
2014-02-01
There has been a surge of diagnosis of autism spectrum disorders (ASD) over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.
DEFF Research Database (Denmark)
Pedersen, Liselotte; Rasmussen, Kirsten; Elsass, Peter
2010-01-01
International research suggests that using formalized risk assessment methods may improve the predictive validity of professionals' predictions of risk of future violence. This study presents data on forensic psychiatric patients discharged from a forensic unit in Denmark in year 2001-2002 (n=107...... and the individual dynamic items strengthen the use of this scheme in clinical practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved) (journal abstract)...
Sudden Cardiac Arrest (SCA) Risk Assessment
... HRS Find a Specialist Share Twitter Facebook SCA Risk Assessment Sudden Cardiac Arrest (SCA) occurs abruptly and without ... people of all ages and health conditions. Start Risk Assessment The Sudden Cardiac Arrest (SCA) Risk Assessment Tool ...
Integrated climate change risk assessment:
DEFF Research Database (Denmark)
Kaspersen, Per Skougaard; Halsnæs, Kirsten
2017-01-01
Risk assessments of flooding in urban areas during extreme precipitation for use in, for example, decision-making regarding climate adaptation, are surrounded by great uncertainties stemming from climate model projections, methods of downscaling and the assumptions of socioeconomic impact models...... to address the complex linkages between the different kinds of data required in assessing climate adaptation. It emphasizes that the availability of spatially explicit data can reduce the overall uncertainty of the risk assessment and assist in identifying key vulnerable assets. The usefulness...... of such a framework is demonstrated by means of a risk assessment of flooding from extreme precipitation for the city of Odense, Denmark. A sensitivity analysis shows how the presence of particularly important assets, such as cultural and historical heritage, may be addressed in assessing such risks. The output...
Construction of a Risk Assessment Model for Rainfall-Induced Landslides
Chen, Yie-Ruey; Tsai, Kuang-Jung; Chen, Jing-Wen; Lin, Wei-Chung
2013-04-01
The unstable geology and steep terrain in the mountainous regions of Taiwan make these areas vulnerable to landslides and debris flow during typhoons and heavy rains. According to the Water Resources Agency, Ministry of Economic Affairs of Taiwan, there were 500 typhoons and over one thousand storms in Taiwan between 1897 and 2011. Natural disasters caused 3.5 billion USD of damage between 1983 and 2011. Thus, the construction of risk assessment model for landslides is essential to disaster prevention. This study employed genetic adaptive neural networks (GANN) with texture analysis in the classification of high-resolution satellite images from which data related to surface conditions in mountainous areas of Taiwan were derived. Ten landslide hazard potential factors are included: slope, geology, elevation, distance from the fault, distance from water, terrain roughness, slope roughness, effective accumulated rainfall and developing situation. By using correlation test, GANN, weight analysis and dangerous value method, levels and probabilities of landslide of the research areas are presented. Then, through geographic information system the landslide potential map is plotted to distinguish high potential regions from low potential regions. Through field surveys, interviews with district officials and a review of relevant literature, the probability of a sediment disaster was estimated as well as the vulnerability of the villages concerned and the degree to which these villages were prepared, to construct a risk evaluation model. The regional risk map was plotted with the help of GIS and the landslide assessment model. The risk assessment model can be used by authorities to make provisions for high-risk areas, to reduce the number of casualties and social costs of sediment disasters.
Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.
Jing, Lijun; Su, Li; Ring, Brian Z
2014-01-01
The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and employed.
Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review
Jing, Lijun; Su, Li; Ring, Brian Z.
2014-01-01
The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort’s ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and
Ethnic background and genetic variation in the evaluation of cancer risk: a systematic review.
Directory of Open Access Journals (Sweden)
Lijun Jing
Full Text Available The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort's ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be
[Assessment of allergenicity of genetically modified food crops].
Schauzu, M; Pöting, A; Rubin, D; Lampen, A
2012-03-01
The placing on the European Union's market of genetically modified crops requires authorization by the European Commission which is based on the proof that the derived foods are as safe as their conventional counterparts. The assessment of potential allergenicity is part of the necessary investigations recommended in the updated Guidance Document of the Scientific Panel on Genetically Modified Organisms (GMO) of the European Food Safety Authority (EFSA), which is based on internationally agreed recommendations. All genetically modified crops which so far have been authorized in the European Union were evaluated by the EFSA GMO Panel which considered it unlikely that their overall allergenicity has been altered.
Characterizing genetic syndromes involved in cancer and radiogenic cancer risk
International Nuclear Information System (INIS)
Unrau, P.; Doerffer, K.
1998-01-01
The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author)
Characterizing genetic syndromes involved in cancer and radiogenic cancer risk
Energy Technology Data Exchange (ETDEWEB)
Unrau, P; Doerffer, K
1998-01-01
The COG project 2806A (1995), reviewed the On-line Mendelian Inheritance in Man (OMIM) database of genetic syndromes to identify those syndromes, genes, and DNA sequences implicated in some way in the cancer process, and especially in radiogenic cancer risk. The current report describes a recent update of the survey in light of two years of further progress in the Human Genome project, and is intended to supply a comprehensive list of those genetic syndromes, genes, DNA sequences and map locations that define genes likely to be involved in cancer risk. Of the 8203 syndromes in OMIM in 1997 June, 814 are associated, even if marginally, with cancer. Of the 814 syndromes so linked, 672 have been mapped to a chromosome, and 476 have been mapped to a chromosome and had a DNA sequence associated with their messenger RNA (or cDNA) sequences. In addition, 35 syndromes have sequences not associated with map locations, and the remaining 107 have neither been mapped nor sequenced. We supply the list of the various genetic syndromes sorted by chromosome location and by OMIM descriptor, together with all the associated but unmapped and unsequenced syndromes. (author) 1 tab., 4 figs.
Assessing Your Weight and Health Risk
... Health Professional Resources Assessing Your Weight and Health Risk Assessment of weight and health risk involves using ... risk for developing obesity-associated diseases or conditions. Risk Factors for Health Topics Associated With Obesity Along ...
Memory Resilience to Alzheimer's Genetic Risk: Sex Effects in Predictor Profiles.
McDermott, Kirstie L; McFall, G Peggy; Andrews, Shea J; Anstey, Kaarin J; Dixon, Roger A
2017-10-01
Apolipoprotein E (APOE) ɛ4 and Clusterin (CLU) C alleles are risk factors for Alzheimer's disease (AD) and episodic memory (EM) decline. Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether (a) memory resilience to AD genetic risk is predicted by biological and other risk markers and (b) the prediction profiles vary by sex and AD risk variant. Using a longitudinal sample of nondemented adults (n = 642, aged 53-95) we focused on memory resilience (over 9 years) to 2 AD risk variants (APOE, CLU). Growth mixture models classified resilience. Random forest analysis, stratified by sex, tested the predictive importance of 22 nongenetic risk factors from 5 domains (n = 24-112). For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience. For women, 9 factors from functional, health, mobility, and lifestyle domains were also predictive. For men, only fewer depressive symptoms was an additional important predictor. The prediction profiles were similar for APOE and CLU. Although several factors predicted resilience in both sexes, a greater number applied only to women. Sex-specific mechanisms and intervention targets are implied. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
BRCA genetic counseling among at-risk Latinas in New York City: new beliefs shape new generation.
Sussner, Katarina M; Edwards, Tiffany; Villagra, Cristina; Rodriguez, M Carina; Thompson, Hayley S; Jandorf, Lina; Valdimarsdottir, Heiddis B
2015-02-01
Despite the life-saving information that genetic counseling can provide for women at hereditary breast and/or ovarian cancer (HBOC) risk, Latinas disproportionately underuse such services. Understanding Latinas' beliefs and attitudes about BRCA genetic counseling may be the key to better health promotion within this underserved, at-risk group. We conducted 12 focus groups (N = 54) with at-risk Latina women in New York City, followed by 30 in-depth interviews among a subset of the focus group women. Both were professionally transcribed, translated where applicable and data analysis was completed by two coders trained in qualitative methods. Results revealed personal and community knowledge about BRCA genetic counseling was relatively low, although women felt largely positive about counseling. The main motivator to undergo genetic counseling was concerns about learning family members' cancer status, while the main barrier was competing demands. Generational differences were apparent, with younger women (approximately machismo, fatalismo, destino) to undergoing genetic counseling. Participants were largely enthusiastic about educational efforts to increase awareness of genetic counseling among Latinos. Revealing the beliefs and attitudes of underserved Latinas may help shape culturally appropriate educational materials and promotion programs to increase BRCA genetic counseling uptake within this underrepresented community.
Hesse-Biber, Sharlene; Flynn, Bailey; Farrelly, Keeva
2018-04-01
The growth of the Internet since the millennium has opened up a myriad of opportunities for education, particularly in medicine. Although those looking for health care information used to have to turn to a face-to-face doctor's visit, an immense library of medical advice is now available at their fingertips. The BRCA genetic predispositions (mutations of the BRCA1 and BRCA2 breast cancer genes) which expose men and women to greater risk of breast, ovarian, and other cancers can be researched extensively online. Several nonprofit organizations now offer online risk assessment and decision-making tools meant to supplement conversation with medical professionals, which in actuality are quickly replacing it. We argue here through a critical qualitative template analysis of several such tools that the discursive frameworks utilized are prone to fearmongering, commercialization, and questionable validity. Left unchecked, these assessment tools could do more harm than good in driving young women especially to take unnecessary extreme surgical action.
Breast cancer risks and risk prediction models.
Engel, Christoph; Fischer, Christine
2015-02-01
BRCA1/2 mutation carriers have a considerably increased risk to develop breast and ovarian cancer. The personalized clinical management of carriers and other at-risk individuals depends on precise knowledge of the cancer risks. In this report, we give an overview of the present literature on empirical cancer risks, and we describe risk prediction models that are currently used for individual risk assessment in clinical practice. Cancer risks show large variability between studies. Breast cancer risks are at 40-87% for BRCA1 mutation carriers and 18-88% for BRCA2 mutation carriers. For ovarian cancer, the risk estimates are in the range of 22-65% for BRCA1 and 10-35% for BRCA2. The contralateral breast cancer risk is high (10-year risk after first cancer 27% for BRCA1 and 19% for BRCA2). Risk prediction models have been proposed to provide more individualized risk prediction, using additional knowledge on family history, mode of inheritance of major genes, and other genetic and non-genetic risk factors. User-friendly software tools have been developed that serve as basis for decision-making in family counseling units. In conclusion, further assessment of cancer risks and model validation is needed, ideally based on prospective cohort studies. To obtain such data, clinical management of carriers and other at-risk individuals should always be accompanied by standardized scientific documentation.
Risk assessment theory, methods, and applications
Rausand, Marvin
2011-01-01
With its balanced coverage of theory and applications along with standards and regulations, Risk Assessment: Theory, Methods, and Applications serves as a comprehensive introduction to the topic. The book serves as a practical guide to current risk analysis and risk assessment, emphasizing the possibility of sudden, major accidents across various areas of practice from machinery and manufacturing processes to nuclear power plants and transportation systems. The author applies a uniform framework to the discussion of each method, setting forth clear objectives and descriptions, while also shedding light on applications, essential resources, and advantages and disadvantages. Following an introduction that provides an overview of risk assessment, the book is organized into two sections that outline key theory, methods, and applications. * Introduction to Risk Assessment defines key concepts and details the steps of a thorough risk assessment along with the necessary quantitative risk measures. Chapters outline...
The issue of risk dilution in risk assessments
International Nuclear Information System (INIS)
Wilmot, R.; Robinson, P.
2004-01-01
This paper explores an issue that was first highlighted more than 20 years ago during an inquiry concerning the Sizeweli B nuclear power station in the UK. In the probabilistic safety assessment for this plant, the proponent had apparently reduced its estimates of risk by admitting to increased uncertainty about the timing of certain events. This situation is counter-intuitive, since an increase in uncertainty about the factors contributing to safety would be expected to lead to less confidence and hence to greater risk. This paradoxical situation was termed 'risk dilution' and it has been a topic of interest to reviewers of safety cases since. The recent international peer review of the Yucca Mountain performance assessments concluded that there was a potential for risk dilution in the assumptions and calculations presented. The next section describes how assumptions about the timing of events and other aspects of an assessment may lead to risk dilution, and this is followed by two examples based on recent performance assessments. The final section discusses how potential problems can be identified in safety cases, and the types of response that a regulator might adopt as a result. (authors)
Directory of Open Access Journals (Sweden)
Okayama M
2016-07-01
Full Text Available Masanobu Okayama,1,2 Taro Takeshima,2 Masanori Harada,3 Ryusuke Ae,4 Eiji Kajii2 1Division of Community Medicine and Medical Education, Kobe University Graduate School of Medicine, Kobe, Hyogo, 2Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University, Shimotsuke, Tochigi, 3Department of Support of Rural Medicine, Yamaguchi Grand Medical Center, Hofu, Yamaguchi, 4Division of Public Health, Center for Community Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan Objective: Disclosing genetic testing results may contribute to the prevention and management of many common diseases. However, whether the presence of a disease influences these effects is unclear. This study aimed to clarify the difference in the effects of disclosing genetic testing results of the risk for developing salt-sensitive hypertension on the behavioral modifications with respect to salt intake in hypertensive and nonhypertensive patients.Methods: A cross-sectional study using a self-administered questionnaire was conducted for outpatients aged >20 years (N=2,237 at six primary care clinics and hospitals in Japan. The main factors assessed were medical histories of hypertension, salt preferences, reduced salt intakes, and behavior modifications for reducing salt intake. Behavioral modifications of participants were assessed using their behavior stages before and after disclosure of the hypothetical genetic testing results. Results: Of the 2,237 participants, 1,644 (73.5% responded to the survey. Of these respondents, 558 (33.9% patients were hypertensive and 1,086 (66.1% were nonhypertensive. After being notified of the result “If with genetic risk”, the nonhypertensive participants were more likely to make positive behavioral modifications compared to the hypertensive patients among all participants and in those aged <65 years (adjusted relative ratio [ad-RR], 1.76; 95% confidence interval, 1.12−2.76 and ad-RR, 1
Forman, Andrea D; Hall, Michael J
2009-01-01
Risk assessment coupled with genetic counseling and testing for the cancer predisposition genes BRCA1 and BRCA2 (BRCA1/2) has become an integral element of comprehensive patient evaluation and cancer risk management in the United States for individuals meeting high-risk criteria for hereditary breast and ovarian cancer (HBOC). For mutation carriers, several options for risk modification have achieved substantial reductions in future cancer risk. However, several recent studies have shown lower rates of BRCA1/2 counseling and testing among minority populations. Here, we explore the role of race/ethnicity in cancer risk assessment, genetic counseling and genetic testing for HBOC and the BRCA1/2 cancer predisposition genes. Barriers to genetic services related to race/ethnicity and underserved populations, including socioeconomic barriers (e.g., time, access, geographic, language/cultural, awareness, cost) and psychosocial barriers (e.g., medical mistrust, perceived disadvantages to genetic services), as well as additional barriers to care once mutation carriers are identified, will be reviewed.
Genetic risk of rhegmatogenous retinal detachment a familial aggregation study
S.L. Go (Sioe Lie); C. Hoyng (Carel); C.C.W. Klaver (Caroline)
2005-01-01
textabstractObjective: To investigate the magnitude of the genetic risk of nonsyndromic rhegmatogenous retinal detachments (RRDs) in a familial aggregation study. Design: Two hundred three consecutive patients with RRD and 461 controls without RRD were ascertained at the Department of Ophthalmology
Risk Assessment in the Maritime Industry
Directory of Open Access Journals (Sweden)
M. Mousavi
2017-02-01
Full Text Available Risk assessment is a well-developed field which many operators are currently applying to improve their operations and reduce their risk exposure. This paper is intended to provide an overview of the risk assessment for mariners in the Maritime transportation. The risks addressed are primarily those affecting the safety of a vessel, facility or operation. The concept of risk is defined, and the methods available to assess the risks associated with an operation are described. Regulatory requirements that have prompted the development of modern risk assessment practices are described, and future regulatory trends are discussed. There are many different analysis techniques and models that have been developed to aid in conducting risk assessments. A key to any successful risk analysis is choosing the right method (or combination of methods for the situation at hand. This is achieved through critical analysis of the available data concerning marine crises. This paper provides a brief introduction to some of the analysis methods available and suggests risk analysis approaches to support different types of decision making within the maritime transportation to cope with crises. Finally, as awareness of risk assessment increases, the benefits which can be realized through its application will continue to increase. Organizations in both the public and the private sector are becoming more and more familiar with the benefits associated with risk-based approaches to managing safety and consequently reducing crisis in maritime transportation.
International Nuclear Information System (INIS)
Selby, P.B.
1977-01-01
Many of the most important findings concerning the genetic effects of radiation have been obtained in the Biology Division of Oak Ridge National Laboratory. The paper focuses on some of the major discoveries made in the Biology Division and on a new method of research that assesses damage to the skeletons of mice whose fathers were irradiated. The results discussed have considerable influence upon estimates of genetic risk in humans from radiation, and an attempt is made to put the estimated amount of genetic damage caused by projected nuclear power development into its proper perspective
Genetic Causes of Recurrent Pregnancy Loss.
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.
Developing a good practice for the review of evidence relevant to GMO risk assessment
DEFF Research Database (Denmark)
Kohl, Christian; Craig, Wendy; Frampton, Geoff
2013-01-01
such research results in a transparent, reproducible and unbiased manner. The EU-funded project GRACE (GMO Risk Assessment and Communication of Evidence) aims to explore, adapt, apply, and promote these tools to enhance accountability in decision-making by providing policy makers with comprehensive, science......-based information on potential impacts (scenarios) of genetically modified plants and their derived products. Furthermore, GRACE will establish an open-access database in order to support the review process, to mirror the evidence synthesis, to assist the dissemination of results and conclusions, as well as to act......, in more general terms, as an information resource on biosafety of genetically modified plants....
Bos, Peter M J; Gottardo, Stefania; Scott-Fordsmand, Janeck J; van Tongeren, Martie; Semenzin, Elena; Fernandes, Teresa F; Hristozov, Danail; Hund-Rinke, Kerstin; Hunt, Neil; Irfan, Muhammad-Adeel; Landsiedel, Robert; Peijnenburg, Willie J G M; Sánchez Jiménez, Araceli; van Kesteren, Petra C E; Oomen, Agnes G
2015-11-27
An engineered nanomaterial (ENM) may actually consist of a population of primary particles, aggregates and agglomerates of various sizes. Furthermore, their physico-chemical characteristics may change during the various life-cycle stages. It will probably not be feasible to test all varieties of all ENMs for possible health and environmental risks. There is therefore a need to further develop the approaches for risk assessment of ENMs. Within the EU FP7 project Managing Risks of Nanoparticles (MARINA) a two-phase risk assessment strategy has been developed. In Phase 1 (Problem framing) a base set of information is considered, relevant exposure scenarios (RESs) are identified and the scope for Phase 2 (Risk assessment) is established. The relevance of an RES is indicated by information on exposure, fate/kinetics and/or hazard; these three domains are included as separate pillars that contain specific tools. Phase 2 consists of an iterative process of risk characterization, identification of data needs and integrated collection and evaluation of data on the three domains, until sufficient information is obtained to conclude on possible risks in a RES. Only data are generated that are considered to be needed for the purpose of risk assessment. A fourth pillar, risk characterization, is defined and it contains risk assessment tools. This strategy describes a flexible and efficient approach for data collection and risk assessment which is essential to ensure safety of ENMs. Further developments are needed to provide guidance and make the MARINA Risk Assessment Strategy operational. Case studies will be needed to refine the strategy.
Directory of Open Access Journals (Sweden)
Peter M. J. Bos
2015-11-01
Full Text Available An engineered nanomaterial (ENM may actually consist of a population of primary particles, aggregates and agglomerates of various sizes. Furthermore, their physico-chemical characteristics may change during the various life-cycle stages. It will probably not be feasible to test all varieties of all ENMs for possible health and environmental risks. There is therefore a need to further develop the approaches for risk assessment of ENMs. Within the EU FP7 project Managing Risks of Nanoparticles (MARINA a two-phase risk assessment strategy has been developed. In Phase 1 (Problem framing a base set of information is considered, relevant exposure scenarios (RESs are identified and the scope for Phase 2 (Risk assessment is established. The relevance of an RES is indicated by information on exposure, fate/kinetics and/or hazard; these three domains are included as separate pillars that contain specific tools. Phase 2 consists of an iterative process of risk characterization, identification of data needs and integrated collection and evaluation of data on the three domains, until sufficient information is obtained to conclude on possible risks in a RES. Only data are generated that are considered to be needed for the purpose of risk assessment. A fourth pillar, risk characterization, is defined and it contains risk assessment tools. This strategy describes a flexible and efficient approach for data collection and risk assessment which is essential to ensure safety of ENMs. Further developments are needed to provide guidance and make the MARINA Risk Assessment Strategy operational. Case studies will be needed to refine the strategy.
Business risks, functions, methods of assessment and ways to reduce risk
Directory of Open Access Journals (Sweden)
A.V. Mihalchuk
2015-06-01
Full Text Available For successful existence in a market economy entrepreneur have to take bold actions, and this increases the risk. The article describes the concept of entrepreneurship and business risk, positive and negative aspects of functions of risk in business. Therefore, it is necessary to assess the risk properly and be able to manage it to achieve the most effective results in the market. In market conditions the problem of assessing and accounting market becomes independent theoretical and practical significance as an important component of the theory and practice of management. Risk - a key element of business activities. Development of risk situations can lead to both the occurrence of adverse effects (losses, lost profits, and positive results for a company in the form of increased profit. This article describes: the concept of entrepreneurship, risk and business risks, characteristic of positive and negative aspects of risk functions in business, methods of assessment and risk reduction, shows formulae and examples you can use to assess risk in an enterprise. Analyzing already established methods of risk assessment a number of rules were proposed in order to reduce business risk.
Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.
2015-01-01
Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039
Hrdová, Edita
2012-01-01
This diploma thesis is focused on companies risk evaluation before endorsement of Loan deriving from business relationships. The aim of this thesis is not only to describe individual steps of risk assessment, but also perfom analysis of particular companies based on available data, i.e. Balance sheet, Profit and Loss statement and external rating and after that propose solution for each company. My analysis will be based on theoretical knowledge, further on experience related to my job role a...
HTGR accident and risk assessment
International Nuclear Information System (INIS)
Silady, F.A.; Everline, C.J.; Houghton, W.J.
1982-01-01
This paper is a synopsis of the high-temperature gas-cooled reactor probabilistic risk assessments (PRAs) performed by General Atomic Company. Principal topics presented include: HTGR safety assessments, peer interfaces, safety research, process gas explosions, quantitative safety goals, licensing applications of PRA, enhanced safety, investment risk assessments, and PRA design integration
Anthropic Risk Assessment on Biodiversity
Piragnolo, M.; Pirotti, F.; Vettore, A.; Salogni, G.
2013-01-01
This paper presents a methodology for risk assessment of anthropic activities on habitats and species. The method has been developed for Veneto Region, in order to simplify and improve the quality of EIA procedure (VINCA). Habitats and species, animals and plants, are protected by European Directive 92/43/EEC and 2009/147/EC but they are subject at hazard due to pollution produced by human activities. Biodiversity risks may conduct to deterioration and disturbance in ecological niches, with consequence of loss of biodiversity. Ecological risk assessment applied on Natura 2000 network, is needed to best practice of management and monitoring of environment and natural resources. Threats, pressure and activities, stress and indicators may be managed by geodatabase and analysed using GIS technology. The method used is the classic risk assessment in ecological context, and it defines the natural hazard as influence, element of risk as interference and vulnerability. Also it defines a new parameter called pressure. It uses risk matrix for the risk analysis on spatial and temporal scale. The methodology is qualitative and applies the precautionary principle in environmental assessment. The final product is a matrix which excludes the risk and could find application in the development of a territorial information system.
Risk assessment and the environment
International Nuclear Information System (INIS)
Fisk, D.J.
1992-01-01
This paper reviews the use of risk assessment techniques in the field of environment protection. I will argue that in some important instances the development of environment policy has been a source of fruitful development of a risk based methodologies. In other cases the importation of risk assessment techniques has proved much more problematic. As the scope of environmental regulation increases so does the possibility of inconsistent and arbitrary solutions to problems. The need for a more systematic approach to the development of environmental regulation has never been stronger, so it is important to understand the reasons for the mixed success of risk assessment. This applies equally to those nations with long traditions of the regulation of private sector industry and those just beginning on this course. The way ahead may be to extend our ideas of how to express risk and uncertainty. Some of the recent cause celebres of environment policy show this challenge very clearly. As an example, this paper will look at the problem of assessing the risk of man-made climate change
Risk assessment and the environment
Energy Technology Data Exchange (ETDEWEB)
Fisk, D J [Department of the Environment (United Kingdom)
1992-07-01
This paper reviews the use of risk assessment techniques in the field of environment protection. I will argue that in some important instances the development of environment policy has been a source of fruitful development of a risk based methodologies. In other cases the importation of risk assessment techniques has proved much more problematic. As the scope of environmental regulation increases so does the possibility of inconsistent and arbitrary solutions to problems. The need for a more systematic approach to the development of environmental regulation has never been stronger, so it is important to understand the reasons for the mixed success of risk assessment. This applies equally to those nations with long traditions of the regulation of private sector industry and those just beginning on this course. The way ahead may be to extend our ideas of how to express risk and uncertainty. Some of the recent cause celebres of environment policy show this challenge very clearly. As an example, this paper will look at the problem of assessing the risk of man-made climate change.
Genomic-based tools for the risk assessment, management, and prevention of type 2 diabetes
Directory of Open Access Journals (Sweden)
Johansen Taber KA
2015-01-01
Full Text Available Katherine A Johansen Taber, Barry D DickinsonDepartment of Science and Biotechnology, American Medical Association, Chicago, IL, USAAbstract: Type 2 diabetes (T2D is a common and serious disorder and is a significant risk factor for the development of cardiovascular disease, neuropathy, nephropathy, retinopathy, periodontal disease, and foot ulcers and amputations. The burden of disease associated with T2D has led to an emphasis on early identification of the millions of individuals at high risk so that management and intervention strategies can be effectively implemented before disease progression begins. With increasing knowledge about the genetic basis of T2D, several genomic-based strategies have been tested for their ability to improve risk assessment, management and prevention. Genetic risk scores have been developed with the intent to more accurately identify those at risk for T2D and to potentially improve motivation and adherence to lifestyle modification programs. In addition, evidence is building that oral antihyperglycemic medications are subject to pharmacogenomic variation in a substantial number of patients, suggesting genomics may soon play a role in determining the most effective therapies. T2D is a complex disease that affects individuals differently, and risk prediction and treatment may be challenging for health care providers. Genomic approaches hold promise for their potential to improve risk prediction and tailor management for individual patients and to contribute to better health outcomes for those with T2D.Keywords: diabetes, genomic, risk prediction, management
Arabkhazaeli, Ali; Ahmadizar, Fariba; Leusink, Maarten; Arets, Hubertus G. M.; Raaijmakers, Jan A. M.; Uiterwaal, Cuno S. P. M.; van der Ent, Cornelis K.; Maitland-van der Zee, Anke-Hilse; Vijverberg, Susanne J. H.
2018-01-01
Background: Several genetic variants have been associated with the susceptibility to allergic disease in adults, but it remains unclear whether these genetic variants are also associated with the onset of allergic disease early in life. The aim of this study was to develop a genetic risk score (GRS)
Nuclear insurance risk assessment using risk-based methodology
International Nuclear Information System (INIS)
Wendland, W.G.
1992-01-01
This paper presents American Nuclear Insurers' (ANI's) and Mutual Atomic Energy Liability Underwriters' (MAELU's) process and experience for conducting nuclear insurance risk assessments using a risk-based methodology. The process is primarily qualitative and uses traditional insurance risk assessment methods and an approach developed under the auspices of the American Society of Mechanical Engineers (ASME) in which ANI/MAELU is an active sponsor. This process assists ANI's technical resources in identifying where to look for insurance risk in an industry in which insurance exposure tends to be dynamic and nonactuarial. The process is an evolving one that also seeks to minimize the impact on insureds while maintaining a mutually agreeable risk tolerance
Simulated Annealing Genetic Algorithm Based Schedule Risk Management of IT Outsourcing Project
Directory of Open Access Journals (Sweden)
Fuqiang Lu
2017-01-01
Full Text Available IT outsourcing is an effective way to enhance the core competitiveness for many enterprises. But the schedule risk of IT outsourcing project may cause enormous economic loss to enterprise. In this paper, the Distributed Decision Making (DDM theory and the principal-agent theory are used to build a model for schedule risk management of IT outsourcing project. In addition, a hybrid algorithm combining simulated annealing (SA and genetic algorithm (GA is designed, namely, simulated annealing genetic algorithm (SAGA. The effect of the proposed model on the schedule risk management problem is analyzed in the simulation experiment. Meanwhile, the simulation results of the three algorithms GA, SA, and SAGA show that SAGA is the most superior one to the other two algorithms in terms of stability and convergence. Consequently, this paper provides the scientific quantitative proposal for the decision maker who needs to manage the schedule risk of IT outsourcing project.
DEFF Research Database (Denmark)
Klefoth, Thomas; Skov, Christian; Krause, Jens
2011-01-01
To showcase the importance of genotype × environment interactions and the presence of predation risk in the experimental assessment of boldness in fish, we investigated boldness in terms of feeding behavior and refuge use in two genetically different populations of juvenile carp (Cyprinus carpio)...
A new definition of Genetic Counseling: National Society of Genetic Counselors' Task Force report.
Resta, Robert; Biesecker, Barbara Bowles; Bennett, Robin L; Blum, Sandra; Hahn, Susan Estabrooks; Strecker, Michelle N; Williams, Janet L
2006-04-01
The Genetic Counseling Definition Task Force of the National Society of Genetic Counselors (NSGC) developed the following definition of genetic counseling that was approved by the NSGC Board of Directors: Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates the following: Interpretation of family and medical histories to assess the chance of disease occurrence or recurrence. Education about inheritance, testing, management, prevention, resources and research. Counseling to promote informed choices and adaptation to the risk or condition. The definition was approved after a peer review process with input from the NSGC membership, genetic professional organizations, the NSGC legal counsel, and leaders of several national genetic advocacy groups.
Cost-benefit as weighed on genetic scales
International Nuclear Information System (INIS)
Grahn, D.
1976-01-01
The genetic cost that may be incurred by exposure to mutagenic agents in the coal and nuclear fuel cycles is assessed, using as a point of departure the presently estimated burden of spontaneously occurring genetic defects in human populations. Risk estimates are necessarily derived from radiation studies, but chemical mutagenic hazards can probably be evaluated relative to the known dose-response relationships of radiation exposure. Cost-benefit analyses for the coal and nuclear fuel cycles are discussed and translated into monetary terms. Coal-associated risks are almost entirely somatic while nuclear risks are somatic and genetic in equal proportions. Dollar costs per man-rem are concluded to be in the $100 range. Pollution abatement costs for the nuclear cycle lie in the range of several hundreds to many thousands of dollars per man-rem reduction. It is considered appropriate to incur such costs, because genetic risks to future generations involve primarily societal and ethical issues rather than economic considerations
What can be offered to couples at (possibly) increased genetic risk?
Read, Andrew P.; Donnai, Dian
2012-01-01
We review the reasons why a couple might seek specialist genetic counselling about a possible reproductive risk and the options available to them. Most commonly, the couple will be concerned about the risk of recurrence of a medical condition that has already occurred in the family. Sometimes, the increased risk may come from their ethnicity or because of a consanguineous marriage, rather than because any problem has occurred previously. The geneticist must identify the exact nature of any pr...
Risk assessment for halogenated solvents
International Nuclear Information System (INIS)
Travis, C.C.
1988-01-01
A recent development in the cancer risk area is the advent of biologically based pharmacokinetic and pharmacodynamic models. These models allow for the incorporation of biological and mechanistic data into the risk assessment process. These advances will not only improve the risk assessment process for halogenated solvents but will stimulate and guide basic research in the biological area
RESIDUAL RISK ASSESSMENT: ETHYLENE OXIDE ...
This document describes the residual risk assessment for the Ethylene Oxide Commercial Sterilization source category. For stationary sources, section 112 (f) of the Clean Air Act requires EPA to assess risks to human health and the environment following implementation of technology-based control standards. If these technology-based control standards do not provide an ample margin of safety, then EPA is required to promulgate addtional standards. This document describes the methodology and results of the residual risk assessment performed for the Ethylene Oxide Commercial Sterilization source category. The results of this analyiss will assist EPA in determining whether a residual risk rule for this source category is appropriate.
Aalfs, Cora M; Dekker, Evelien; Tanis, Pieter J; Smets, Ellen M
2017-01-01
Background Nongenetic health providers may lack the relevant knowledge, experience, and communication skills to adequately detect familial colorectal cancer (CRC), despite a positive attitude toward the assessment of history of cancer in a family. Specific training may enable them to more optimally refer patients to genetic counseling. Objective The aim of this study was to develop an e-learning module for gastroenterologists and surgeons (in training) aimed at improving attitudes, knowledge, and comprehension of communication skills, and to assess the feasibility of the e-learning module for continued medical education of these specialists. Methods A focus group helped to inform the development of a training framework. The e-learning module was then developed, followed by a feasibility test among a group of surgeons-in-training (3rd- and 4th-year residents) and then among gastroenterologists, using pre- and posttest questionnaires. Results A total of 124 surgeons-in-training and 14 gastroenterologists participated. The e-learning was positively received (7.5 on a scale of 1 to 10). Between pre- and posttest, attitude increased significantly on 6 out of the 10 items. Mean test score showed that knowledge and comprehension of communication skills improved significantly from 49% to 72% correct at pretest to 67% to 87% correct at posttest. Conclusions This study shows the feasibility of a problem-based e-learning module to help surgeons-in-training and gastroenterologists in recognizing a hereditary predisposition in patients with CRC. The e-learning led to improvements in attitude toward the assessment of cancer family history, knowledge on criteria for referral to genetic counseling for CRC, and comprehension of communication skills. PMID:29254907
Risk assessment: An employer's perspective
International Nuclear Information System (INIS)
Williams, K.C.
1992-01-01
There is no question that a careful assessment of risk is essential for safe industrial operations. For that reason, a thoughtful analysis of the effectiveness of available risk assessment technologies is prerequisite for responsible corporate decision making. An 'employer's' perspective on risk assessment cannot be constrained by any artificial restrictions which that term may imply. In reality, all those who are involved in the execution of an industrial enterprise: managers, regulators, the affected public, and especially those employees exposed to hazards, are necessarily partners in assessment of risk. The perspective of this paper is that of the oil and gas industry, in which the author's organization, Exxon Company, International, participates. The paper addresses what Exxon requires to assess and manage risk in its worldwide operations. The author is aware, however, through contacts with industry colleagues, that some of Exxon's initiatives are representative of similar actions being taken by others. 1992 is the European Year of Safety, Health and Hygiene, coinciding with the United Kingdom's Presidency of the European Council. It is also the year in which new 'goal-setting' regulations covering safety in the U.K. offshore oil industry were put forward by the Health and Safety Commission. These regulations, based largely on Lord Cullen's recommendations following the Piper Alpha tragedy, set the pace for safety in the British North Sea and will significantly impact the safety of offshore oil installations worldwide. The requirement for risk assessment, using a systematic process of analysing and evaluating risk, is a key component of this safety regime
Risk assessment: An employer's perspective
Energy Technology Data Exchange (ETDEWEB)
Williams, K C [Exxon International (United States)
1992-07-01
There is no question that a careful assessment of risk is essential for safe industrial operations. For that reason, a thoughtful analysis of the effectiveness of available risk assessment technologies is prerequisite for responsible corporate decision making. An 'employer's' perspective on risk assessment cannot be constrained by any artificial restrictions which that term may imply. In reality, all those who are involved in the execution of an industrial enterprise: managers, regulators, the affected public, and especially those employees exposed to hazards, are necessarily partners in assessment of risk. The perspective of this paper is that of the oil and gas industry, in which the author's organization, Exxon Company, International, participates. The paper addresses what Exxon requires to assess and manage risk in its worldwide operations. The author is aware, however, through contacts with industry colleagues, that some of Exxon's initiatives are representative of similar actions being taken by others. 1992 is the European Year of Safety, Health and Hygiene, coinciding with the United Kingdom's Presidency of the European Council. It is also the year in which new 'goal-setting' regulations covering safety in the U.K. offshore oil industry were put forward by the Health and Safety Commission. These regulations, based largely on Lord Cullen's recommendations following the Piper Alpha tragedy, set the pace for safety in the British North Sea and will significantly impact the safety of offshore oil installations worldwide. The requirement for risk assessment, using a systematic process of analysing and evaluating risk, is a key component of this safety regime.
Identification of Hotspots of Genetic Risk for Type 2 Diabetes Using GIS Methods
BACKGROUND: Having the ability to scan the entire country for potential "hotspots" with increased risk of developing chronic diseases due to various environmental, demographic, and genetic susceptibility factors may inform risk management decisions and enable better env...
Associations between genetic risk, functional brain network organization and neuroticism
Servaas, Michelle N.; Geerligs, Linda; Bastiaansen, Jojanneke A.; Renken, Remco J.; Marsman, Jan-Bernard C.; Nolte, Ilja M.; Ormel, Johan; Aleman, Andre; Riese, Harriette
2017-01-01
Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on
Genetic risk of rhegmatogenous retinal detachment: a familial aggregation study.
Go, S.L.; Hoyng, C.B.; Klaver, C.C.W.
2005-01-01
OBJECTIVE: To investigate the magnitude of the genetic risk of nonsyndromic rhegmatogenous retinal detachments (RRDs) in a familial aggregation study. DESIGN: Two hundred three consecutive patients with RRD and 461 controls without RRD were ascertained at the Department of Ophthalmology of the
Directory of Open Access Journals (Sweden)
Dominika Sieradzka
Full Text Available Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS, as well as specific single nucleotide polymorphisms (SNPs previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ, were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10⁻⁴ and rs9960767 (p-value = 6.23×10⁻⁴. Replication in an independent sample of 16-year-olds (N = 3,427 assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q, a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test
RELEVANCE OF PROCESS RISK ASSESSMENT IN AIRLINES
Oksana G. Feoktistova; Igor K. Turkin; Sergey V. Barinov
2017-01-01
The notion of “the concept on assumed risk” that took over from the outdated concept of absolute security is analyzed, the increasing significance of operating risk assessment at the present stage is noted. Some basic risk assessment techniques are considered. Matrix technique of risk assessment is considered more thoroughly, and it may be used in risk assessment of airlines in the context of labour protection management system.The ability to correctly assess risks and develop appropriate pre...
PCSK9 genetic variants and risk of type 2 diabetes
DEFF Research Database (Denmark)
Schmidt, Amand F; Swerdlow, Daniel I; Holmes, Michael V
2017-01-01
used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using...... diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we...... a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL...
A framework for combining social impact assessment and risk assessment
Mahmoudi, Hossein; Renn, Ortwin; Vanclay, Frank; Hoffmann, Volker; Karami, Ezatollah
An increasing focus on integrative approaches is one of the current trends in impact assessment. There is potential to combine impact assessment with various other forms of assessment, such as risk assessment, to make impact assessment and the management of social risks more effective. We identify
A framework for combining social impact assessment and risk assessment
Mahmoudi, Hossein; Renn, Ortwin; Vanclay, Frank; Hoffmann, Volker; Karami, Ezatollah
2013-01-01
An increasing focus on integrative approaches is one of the current trends in impact assessment. There is potential to combine impact assessment with various other forms of assessment, such as risk assessment, to make impact assessment and the management of social risks more effective. We identify
Risk indices in comparative risk assessment studies
International Nuclear Information System (INIS)
Hubert, P.
1984-01-01
More than a decade ago the development of comparative risk assessment studies aroused overwhelming interest. There was no doubt that data on the health and safety aspects of energy systems would greatly benefit, or even end, the debate on nuclear energy. Although such attempts are still strongly supported, the rose-coloured expectations of the early days have faded. The high uncertainties, and the contradictory aspect, of the first results might explain this evolution. The loose connection between the range of computed risk indices and the questions on which the debate was focused is another reason for this decline in interest. Important research work is being carried out aiming at reducing the different kinds of uncertainties. Rather than the uncertainties, the paper considers the meaning of available risk indices and proposes more significant indices with respect to the goals of risk assessment. First, the indices which are of frequent use in comparative studies are listed. The stress is put on a French comparative study from which most examples are drawn. Secondly, the increase in magnitude of the indices and the decrease in the attributability of the risk to a given system is shown to be a consequence of the trend towards more comprehensive analyses. Thirdly, the ambiguity of such indices as the collective occupational risk is underlined, and a possible solution is suggested. Whenever risk assessments are related to pragmatic decision making problems it is possible to find satisfactory risk indices. The development of cost-effectiveness analyses and the proposals for quantitative safety goals clearly demonstrate this point. In the field of comparison of social impacts some proposals are made, but there remain some gaps still to be filled. (author)
Sugden, P B; Cameron, B; Luciani, F; Lloyd, A R
2014-08-01
Genetic resistance to specific infections is well recognized. In hepatitis C virus (HCV) infection, genetic polymorphisms in IL-28B and the killer cell immunoglobulin-like receptors (KIR) and their HLA class I ligands have been shown to affect clearance of the virus following infection. There are limited data regarding resistance to established HCV infection. Reliable quantification of repeated exposure in high-risk populations, such as injecting drug users (IDU), is a key limitation of previous studies of resistance. Behavioural data and DNA from IDU (n = 210) in the Hepatitis C Incidence and Transmission Study in prisons (HITS-p) cohort were genotyped for polymorphisms in: IL-28B, peptidyl-prolyl isomerase A (PPIA), HLA-C and KIR2. To quantify risk, a composite risk index based on factors predictive of incident HCV infection was derived. Logistic regression analysis revealed the risk index was strongly associated with incident HCV infection (P C1, or their combination. A framework for the investigation of genetic determinants of resistance to HCV infection has been developed. Several candidate gene associations were investigated and excluded. Further investigation of genetic determinants of resistance to HCV infection is warranted. © 2014 John Wiley & Sons Ltd.
Aspects regarding explosion risk assessment
Directory of Open Access Journals (Sweden)
Părăian Mihaela
2017-01-01
Full Text Available Explosive risk occurs in all activities involving flammable substances in the form of gases, vapors, mists or dusts which, in mixture with air, can generate an explosive atmosphere. As explosions can cause human losses and huge material damage, the assessment of the explosion risk and the establishment of appropriate measures to reduce it to acceptable levels according to the standards and standards in force is of particular importance for the safety and health of people and goods.There is no yet a recognized method of assessing the explosion risk, but regardless of the applied method, the likelihood of an explosive atmosphere occurrence has to be determined, together with the occurrence of an efficient ignition source and the magnitude of foreseeable consequences. In assessment processes, consequences analysis has a secondary importance since it’s likely that explosions would always involve considerable damage, starting from important material damages and up to human damages that could lead to death.The purpose of the work is to highlight the important principles and elements to be taken into account for a specific risk assessment. An essential element in assessing the risk of explosion in workplaces where explosive atmospheres may occur is technical installations and personal protective equipment (PPE that must be designed, manufactured, installed and maintained so that they cannot generate a source of ignition. Explosion prevention and protection requirements are governed by specific norms and standards, and a main part of the explosion risk assessment is related to the assessment of the compliance of the equipment / installation with these requirements.
Martin, Joanna; Tilling, Kate; Hubbard, Leon; Stergiakouli, Evie; Thapar, Anita; Davey Smith, George; O'Donovan, Michael C; Zammit, Stanley
2016-06-15
Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
Evolutionary Perspectives on Genetic and Environmental Risk Factors for Psychiatric Disorders.
Keller, Matthew C
2018-05-07
Evolutionary medicine uses evolutionary theory to help elucidate why humans are vulnerable to disease and disorders. I discuss two different types of evolutionary explanations that have been used to help understand human psychiatric disorders. First, a consistent finding is that psychiatric disorders are moderately to highly heritable, and many, such as schizophrenia, are also highly disabling and appear to decrease Darwinian fitness. Models used in evolutionary genetics to understand why genetic variation exists in fitness-related traits can be used to understand why risk alleles for psychiatric disorders persist in the population. The usual explanation for species-typical adaptations-natural selection-is less useful for understanding individual differences in genetic risk to disorders. Rather, two other types of models, mutation-selection-drift and balancing selection, offer frameworks for understanding why genetic variation in risk to psychiatric (and other) disorders exists, and each makes predictions that are now testable using whole-genome data. Second, species-typical capacities to mount reactions to negative events are likely to have been crafted by natural selection to minimize fitness loss. The pain reaction to tissue damage is almost certainly such an example, but it has been argued that the capacity to experience depressive symptoms such as sadness, anhedonia, crying, and fatigue in the face of adverse life situations may have been crafted by natural selection as well. I review the rationale and strength of evidence for this hypothesis. Evolutionary hypotheses of psychiatric disorders are important not only for offering explanations for why psychiatric disorders exist, but also for generating new, testable hypotheses and understanding how best to design studies and analyze data.
Smith, Michelle K; Knight, Jennifer K
2012-05-01
To help genetics instructors become aware of fundamental concepts that are persistently difficult for students, we have analyzed the evolution of student responses to multiple-choice questions from the Genetics Concept Assessment. In total, we examined pretest (before instruction) and posttest (after instruction) responses from 751 students enrolled in six genetics courses for either majors or nonmajors. Students improved on all 25 questions after instruction, but to varying degrees. Notably, there was a subgroup of nine questions for which a single incorrect answer, called the most common incorrect answer, was chosen by >20% of students on the posttest. To explore response patterns to these nine questions, we tracked individual student answers before and after instruction and found that particular conceptual difficulties about genetics are both more likely to persist and more likely to distract students than other incorrect ideas. Here we present an analysis of the evolution of these incorrect ideas to encourage instructor awareness of these genetics concepts and provide advice on how to address common conceptual difficulties in the classroom.
The risk for cancer and genetic abnormalities after radioiodine treatment of hyperthyroidism
International Nuclear Information System (INIS)
Reiners, C.
1997-01-01
According to recent studies, the risk for thyroid cancer is not increased after radioiodine treatment in patients with hyperthyroidism. Only the risk of cancer of the stomach seems to be increased slightly in patents treated with I-131 because of functional autonomy. However, the risk for gastric cancer is not increased after higher activities of I-131 because of thyroid cancer. There is no increased risk for genetic abnormalities after radioiodine treatment of hyperthyroidism. (orig.) [de
Faulks, L K; Östman, Ö
2016-04-01
This study assessed the major histocompatibility complex (MHC) and neutral genetic variation and structure in two percid species, perch Perca fluviatilis and zander Sander lucioperca, in a unique brackish ecosystem, the Baltic Sea. In addition, to assess the importance of MHC diversity to disease susceptibility in these populations, comparisons were made to an introduced, disease susceptible, P. fluviatilis population in Australia. Eighty-three MHC class II B exon 2 variants were amplified: 71 variants from 92 P. fluviatilis samples, and 12 variants from 82 S. lucioperca samples. Microsatellite and MHC data revealed strong spatial genetic structure in S. lucioperca, but not P. fluviatilis, across the Baltic Sea. Both microsatellite and MHC data showed higher levels of genetic diversity in P. fluviatilis from the Baltic Sea compared to Australia, which may have facilitated the spread of an endemic virus, EHNV in the Australian population. The relatively high levels of genetic variation in the Baltic Sea populations, together with spatial genetic structure, however, suggest that there currently seems to be little risk of disease epidemics in this system. To ensure this remains the case in the face of ongoing environmental changes, fisheries and habitat disturbance, the conservation of local-scale genetic variation is recommended. © 2016 The Fisheries Society of the British Isles.
Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Zhang, Ben; Long, Jirong; Shu, Xiao-Ou; Schmidt, Marjanka K; Milne, Roger L; García-Closas, Montserrat; Chang-Claude, Jenny; Lindstrom, Sara; Bojesen, Stig E; Ahsan, Habibul; Aittomäki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Beeghly-Fadiel, Alicia; Benitez, Javier; Blomqvist, Carl; Bogdanova, Natalia V; Børresen-Dale, Anne-Lise; Brand, Judith; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Cai, Qiuyin; Casey, Graham; Chenevix-Trench, Georgia; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Dörk, Thilo; Dumont, Martine; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Gammon, Marilie; Giles, Graham G; Guénel, Pascal; Haiman, Christopher A; Hamann, Ute; Harrington, Patricia; Hartman, Mikael; Hooning, Maartje J; Hopper, John L; Jakubowska, Anna; Jasmine, Farzana; John, Esther M; Johnson, Nichola; Kabisch, Maria; Khan, Sofia; Kibriya, Muhammad; Knight, Julia A; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Luben, Robert; Lubinski, Jan; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; McLean, Catriona; Meijers-Heijboer, Hanne; Meindl, Alfons; Miao, Hui; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Neven, Patrick; Olson, Janet E; Perkins, Barbara; Peterlongo, Paolo; Phillips, Kelly-Anne; Pylkäs, Katri; Rudolph, Anja; Santella, Regina; Sawyer, Elinor J; Schmutzler, Rita K; Schoemaker, Minouk; Shah, Mitul; Shrubsole, Martha; Southey, Melissa C; Swerdlow, Anthony J; Toland, Amanda E; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Ursin, Giske; Van Der Luijt, Rob B; Verhoef, Senno; Wang-Gohrke, Shan; Whittemore, Alice S; Winqvist, Robert; Pilar Zamora, M; Zhao, Hui; Dunning, Alison M; Simard, Jacques; Hall, Per; Kraft, Peter; Pharoah, Paul; Hunter, David; Easton, Douglas F; Zheng, Wei
2016-05-01
Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D susceptibility loci and evaluated its relation to breast cancer risk using the data from two consortia, including 62,328 breast cancer patients and 83,817 controls of European ancestry. Unconditional logistic regression models were used to derive adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) to measure the association of breast cancer risk with T2D GRS or T2D-associated genetic risk variants. Meta-analyses were conducted to obtain summary ORs across all studies. The T2D GRS was not found to be associated with breast cancer risk, overall, by menopausal status, or for estrogen receptor positive or negative breast cancer. Three T2D associated risk variants were individually associated with breast cancer risk after adjustment for multiple comparisons using the Bonferroni method (at p associated with the risk of both T2D and breast cancer. However, overall genetic susceptibility to T2D may not be related to breast cancer risk.
Invited commentary: genetic variants and individual- and societal-level risk factors.
Coughlin, Steven S
2010-01-01
Over the past decade, leading epidemiologists have noted the importance of social factors in studying and understanding the distribution and determinants of disease in human populations; but to what extent are epidemiologic studies integrating genetic information and other biologic variables with information about individual-level risk factors and group-level or societal factors related to the broader residential, behavioral, or cultural context? There remains a need to consider ways to integrate genetic information with social and contextual information in epidemiologic studies, partly to combat the overemphasis on the importance of genetic factors as determinants of disease in human populations. Even in genome-wide association studies of coronary heart disease and other common complex diseases, only a small proportion of heritability is explained by the genetic variants identified to date. It is possible that familial clustering due to genetic factors has been overestimated and that important environmental or social influences (acting alone or in combination with genetic variants) have been overlooked. The accompanying article by Bressler et al. (Am J Epidemiol. 2010;171(1):14-23) highlights some of these important issues.
Identification of potentially hazardous human gene products in GMO risk assessment.
Bergmans, Hans; Logie, Colin; Van Maanen, Kees; Hermsen, Harm; Meredyth, Michelle; Van Der Vlugt, Cécile
2008-01-01
Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.
Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms
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
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
Chlorine transportation risk assessment
International Nuclear Information System (INIS)
Lautkaski, Risto; Mankamo, Tuomas.
1977-02-01
An assessment has been made on the toxication risk of the population due to the bulk rail transportation of liquid chlorine in Finland. Fourteen typical rail accidents were selected and their probability was estimated using the accident file of the Finnish State Railways. The probability of a chlorine leak was assessed for each type of accident separately using four leak size categories. The assessed leakage probability was dominated by station accidents, especially by collisions of a chlorine tanker and a locomotive. Toxication hazard areas were estimated for the leak categories. A simple model was constructed to describe the centring of the densely populated areas along the railway line. A comparison was made between the obtained risk and some other risks including those due to nuclear reactor accidents. (author)
Probabilistic risk assessment, Volume I
International Nuclear Information System (INIS)
Anon.
1982-01-01
This book contains 158 papers presented at the International Topical Meeting on Probabilistic Risk Assessment held by the American Nuclear Society (ANS) and the European Nuclear Society (ENS) in Port Chester, New York in 1981. The meeting was second in a series of three. The main focus of the meeting was on the safety of light water reactors. The papers discuss safety goals and risk assessment. Quantitative safety goals, risk assessment in non-nuclear technologies, and operational experience and data base are also covered. Included is an address by Dr. Chauncey Starr
Risk assessment in maritime transportation
International Nuclear Information System (INIS)
Soares, C. Guedes; Teixeira, A.P.
2001-01-01
A review is presented of different approaches to quantify the risk in maritime transportation. The discussion of several accident statistics provides a global assessment of the risk levels and its differentiation in ship types and main types of ship losses. Early studies in the probability of ship loss by foundering and capsizing are reviewed. The approaches used to assess the risk of structural design are addressed. Finally a brief account is given of recent development of using formal safety assessments to support decision making on legislation applicable internationally to maritime transportation
Framework for ecological risk assessment
International Nuclear Information System (INIS)
Rodier, D.; Norton, S.
1992-02-01
Increased interest in ecological issues such as global climate change, habitat loss, acid deposition, reduced biological diversity, and the ecological impacts of pesticides and toxic chemicals prompts this U.S. Environmental Protection Agency (EPA) report, A Framework for Ecological Risk Assessment ('Framework Report'). The report describes basic elements, or a framework, for evaluating scientific information on the adverse effects of physical and chemical stressors on the environment. The framework offers starting principles and a simple structure as guidance for current ecological risk assessments and as a foundation for future EPA proposals for risk assessment guidelines
Rolison, Jonathan J; Hanoch, Yaniv; Miron-Shatz, Talya
2012-07-01
Genetic testing for gene mutations associated with specific cancers provides an opportunity for early detection, surveillance, and intervention (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic testing refer to the risk of developing a specific disease within one's lifetime, and evidence suggests that this is important for the medical choices people make, as well as their future family and financial plans. The present studies tested whether adult men understand the lifetime risks of prostate cancer informed by genetic testing. In 2 experiments, adult men were asked to interpret the lifetime risk information provided in statements about risks of prostate cancer. Statement format was manipulated such that the most appropriate interpretation of risk statements referred to an absolute risk of cancer in experiment 1 and a relative risk in experiment 2. Experiment 1 revealed that few men correctly interpreted the lifetime risks of cancer when these refer to an absolute risk of cancer, and numeracy levels positively predicted correct responding. The proportion of correct responses was greatly improved in experiment 2 when the most appropriate interpretation of risk statements referred instead to a relative rather than an absolute risk, and numeracy levels were less involved. Understanding of lifetime risk information is often poor because individuals incorrectly believe that these refer to relative rather than absolute risks of cancer.
Risk assessment instruments in clinical practice.
Côté, Gilles; Crocker, Anne G; Nicholls, Tonia L; Seto, Michael C
2012-04-01
To determine whether the items in one of the most widely validated instruments of violence risk assessment, the Historical-Clinical-Risk Management-20 (HCR-20), are used in review board hearings to assess the risk of violence by people found Not Criminally Responsible on account of Mental Disorder (NCRMD). This study was conducted from October 2004 to August 2006 in Quebec's sole forensic psychiatric hospital and 2 large civil psychiatric hospitals designated for the care of people declared NCRMD in the Montreal metropolitan area. The risk assessments presented by clinicians at annual review board hearings and the boards' rationale for the release or detention of people found NCRMD were contrasted with the risk assessments conducted by the research team using the HCR-20. The final sample was comprised of 96 men. Very few of the risk factors identified by prior research (HCR-20 items) were mentioned in the hearing process, whether in clinical reports, discussions during the hearing, or in the disposition justification. The findings confirm that there remains a significant gap between research evidence and risk assessment practice.
Assessing Date Palm Genetic Diversity Using Different Molecular Markers.
Atia, Mohamed A M; Sakr, Mahmoud M; Adawy, Sami S
2017-01-01
Molecular marker technologies which rely on DNA analysis provide powerful tools to assess biodiversity at different levels, i.e., among and within species. A range of different molecular marker techniques have been developed and extensively applied for detecting variability in date palm at the DNA level. Recently, the employment of gene-targeting molecular marker approaches to study biodiversity and genetic variations in many plant species has increased the attention of researchers interested in date palm to carry out phylogenetic studies using these novel marker systems. Molecular markers are good indicators of genetic distances among accessions, because DNA-based markers are neutral in the face of selection. Here we describe the employment of multidisciplinary molecular marker approaches: amplified fragment length polymorphism (AFLP), start codon targeted (SCoT) polymorphism, conserved DNA-derived polymorphism (CDDP), intron-targeted amplified polymorphism (ITAP), simple sequence repeats (SSR), and random amplified polymorphic DNA (RAPD) to assess genetic diversity in date palm.
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.
Directory of Open Access Journals (Sweden)
Yumie Takata
Full Text Available Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1 concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85. SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR = 3.95, 95% confidence intervals (CI = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58, but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69. Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1
Zhang, L; Ye, Y; Tu, H; Hildebrandt, M A; Zhao, L; Heymach, J V; Roth, J A; Wu, X
2017-05-01
Genetic variations in MicroRNA (miRNA) binding sites may alter structural accessibility of miRNA binding sites to modulate risk of cancer. This large-scale integrative multistage study was aimed to evaluate the interplay of genetic variations in miRNA binding sites of iron regulatory pathway, dietary iron intake and lung cancer (LC) risk. The interplay of genetic variant, dietary iron intake and LC risk was assessed in large-scale case-control study. Functional characterization of the validated SNP and analysis of target miRNAs were performed. We found that the miRNA binding site SNP rs1062980 in 3' UTR of Iron-Responsive Element Binding protein 2 gene (IREB2) was associated with a 14% reduced LC risk (P value = 4.9×10 - 9). Comparing to AA genotype, GG genotype was associated with a 27% reduced LC risk. This association was evident in males and ever-smokers but not in females and never-smokers. Higher level of dietary iron intake was significantly associated with 39% reduced LC risk (P value = 2.0×10 - 8). This association was only present in individuals with AG + AA genotypes with a 46% reduced risk (P value = 1.0×10 - 10), but not in GG genotype. The eQTL-analysis showed that rs1062980 significantly alters IREB2 expression level. Rs1062980 is predicted to alter a miR-29 binding site on IREB2 and indeed the expression of miR-29 is inversely correlated with IREB2 expression. Further, we found that higher circulating miR-29a level was significantly associated with 78% increased LC risk. The miRNA binding site SNP rs1062980 in iron regulatory pathway, which may alter the expression of IREB2 potentially through modulating the binding of miR-29a, together with dietary iron intake may modify risk of LC both individually and jointly. These discoveries reveal novel pathway for understanding lung cancer tumorigenesis and risk stratification. © The Author 2017. Published by Oxford University Press on behalf of the European Society for
Reevaluating Interrater Reliability in Offender Risk Assessment
van der Knaap, L.M.; Leenarts, L.E.W.; Born, M.P.; Oosterveld, P.
2012-01-01
Offender risk and needs assessment, one of the pillars of the risk-need-responsivity model of offender rehabilitation, usually depends on raters assessing offender risk and needs. The few available studies of interrater reliability in offender risk assessment are, however, limited in the
Genetic risks associated with radiation exposures during space flight
International Nuclear Information System (INIS)
Grahn, D.
1983-01-01
Although the genetic risks of space radiation do not pose a significant hazard to the general population, the risks may be very important to the individual astronaut. The present paper summarizes some experimental results on the induction of dominant lethal mutations and chromosomal damage in the first generation which may be used in the prediction of the genetic risks of radiation exposures of space crews. Young adult male mice were exposed to single, weekly and continuous doses of gamma rays, neutrons in single doses and weekly exposures and continuous doses of Pu-239 alpha particles. Evaluation of fetal survival rates in females mated to the exposed males shows the mutation rate in individuals exposed to gamma rays to decline as the exposure period is prolonged and the dose rate is reduced, while the response to neutrons is in the opposite direction. Cytological determinations show the rate of balanced chromosomal translocations to drop as gamma ray exposures change from one-time to continuous, however little or no dose rate effect is seen with neutron radiation and alpha particle exposure shows no regular dose-response. Based on the above results, it is predicted that the rate of dominant mutations and transmissible chromosome aberrations in astronauts on a 100-day mission will increase by 4.5 to 41.25 percent over the spontaneous rate. 35 references
Quantitative risk assessment system (QRAS)
Weinstock, Robert M (Inventor); Smidts, Carol S (Inventor); Mosleh, Ali (Inventor); Chang, Yung-Hsien (Inventor); Swaminathan, Sankaran (Inventor); Groen, Francisco J (Inventor); Tan, Zhibin (Inventor)
2001-01-01
A quantitative risk assessment system (QRAS) builds a risk model of a system for which risk of failure is being assessed, then analyzes the risk of the system corresponding to the risk model. The QRAS performs sensitivity analysis of the risk model by altering fundamental components and quantifications built into the risk model, then re-analyzes the risk of the system using the modifications. More particularly, the risk model is built by building a hierarchy, creating a mission timeline, quantifying failure modes, and building/editing event sequence diagrams. Multiplicities, dependencies, and redundancies of the system are included in the risk model. For analysis runs, a fixed baseline is first constructed and stored. This baseline contains the lowest level scenarios, preserved in event tree structure. The analysis runs, at any level of the hierarchy and below, access this baseline for risk quantitative computation as well as ranking of particular risks. A standalone Tool Box capability exists, allowing the user to store application programs within QRAS.
Ecosystem services as assessment endpoints for ecological risk assessment.
Munns, Wayne R; Rea, Anne W; Suter, Glenn W; Martin, Lawrence; Blake-Hedges, Lynne; Crk, Tanja; Davis, Christine; Ferreira, Gina; Jordan, Steve; Mahoney, Michele; Barron, Mace G
2016-07-01
Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag
Vos, Joel; Stiggelbout, Anne M.; Oosterwijk, Jan; Gomez-Garcia, Encarna; Menko, Fred; Collee, J. Margriet; van Asperen, Christi J.; Tibben, Aad
Purpose: Genetic counseling may help counselees understand their genetic risk of developing breast/ovarian cancer. However, many studies have shown that their perception of their risks is inaccurate. Information-oriented variables often predicted the level of accuracy, focusing on specific processes
Ducrot, Virginie; Ashauer, Roman; Bednarska, Agnieszka J; Hinarejos, Silvia; Thorbek, Pernille; Weyman, Gabriel
2016-01-01
Recent guidance identified toxicokinetic-toxicodynamic (TK-TD) modeling as a relevant approach for risk assessment refinement. Yet, its added value compared to other refinement options is not detailed, and how to conduct the modeling appropriately is not explained. This case study addresses these issues through 2 examples of individual-level risk assessment for 2 hypothetical plant protection products: 1) evaluating the risk for small granivorous birds and small omnivorous mammals of a single application, as a seed treatment in winter cereals, and 2) evaluating the risk for fish after a pulsed treatment in the edge-of-field zone. Using acute test data, we conducted the first tier risk assessment as defined in the European Food Safety Authority (EFSA) guidance. When first tier risk assessment highlighted a concern, refinement options were discussed. Cases where the use of models should be preferred over other existing refinement approaches were highlighted. We then practically conducted the risk assessment refinement by using 2 different models as examples. In example 1, a TK model accounting for toxicokinetics and relevant feeding patterns in the skylark and in the wood mouse was used to predict internal doses of the hypothetical active ingredient in individuals, based on relevant feeding patterns in an in-crop situation, and identify the residue levels leading to mortality. In example 2, a TK-TD model accounting for toxicokinetics, toxicodynamics, and relevant exposure patterns in the fathead minnow was used to predict the time-course of fish survival for relevant FOCUS SW exposure scenarios and identify which scenarios might lead to mortality. Models were calibrated using available standard data and implemented to simulate the time-course of internal dose of active ingredient or survival for different exposure scenarios. Simulation results were discussed and used to derive the risk assessment refinement endpoints used for decision. Finally, we compared the
Hanford Site baseline risk assessment methodology
International Nuclear Information System (INIS)
1993-03-01
This methodology has been developed to prepare human health and environmental evaluations of risk as part of the Comprehensive Environmental Response, Compensation, and Liability Act remedial investigations (RIs) and the Resource Conservation and Recovery Act facility investigations (FIs) performed at the Hanford Site pursuant to the Hanford Federal Facility Agreement and Consent Order referred to as the Tri-Party Agreement. Development of the methodology has been undertaken so that Hanford Site risk assessments are consistent with current regulations and guidance, while providing direction on flexible, ambiguous, or undefined aspects of the guidance. The methodology identifies Site-specific risk assessment considerations and integrates them with approaches for evaluating human and environmental risk that can be factored into the risk assessment program supporting the Hanford Site cleanup mission. Consequently, the methodology will enhance the preparation and review of individual risk assessments at the Hanford Site
DEFF Research Database (Denmark)
Zhao, Zhiguo; Wen, Wanqing; Michailidou, Kyriaki
2016-01-01
PURPOSE: Type 2 diabetes (T2D) has been reported to be associated with an elevated risk of breast cancer. It is unclear, however, whether this association is due to shared genetic factors. METHODS: We constructed a genetic risk score (GRS) using risk variants from 33 known independent T2D suscept...
Douma, Kirsten Freya Lea; Aalfs, Cora M; Dekker, Evelien; Tanis, Pieter J; Smets, Ellen M
2017-12-18
Nongenetic health providers may lack the relevant knowledge, experience, and communication skills to adequately detect familial colorectal cancer (CRC), despite a positive attitude toward the assessment of history of cancer in a family. Specific training may enable them to more optimally refer patients to genetic counseling. The aim of this study was to develop an e-learning module for gastroenterologists and surgeons (in training) aimed at improving attitudes, knowledge, and comprehension of communication skills, and to assess the feasibility of the e-learning module for continued medical education of these specialists. A focus group helped to inform the development of a training framework. The e-learning module was then developed, followed by a feasibility test among a group of surgeons-in-training (3rd- and 4th-year residents) and then among gastroenterologists, using pre- and posttest questionnaires. A total of 124 surgeons-in-training and 14 gastroenterologists participated. The e-learning was positively received (7.5 on a scale of 1 to 10). Between pre- and posttest, attitude increased significantly on 6 out of the 10 items. Mean test score showed that knowledge and comprehension of communication skills improved significantly from 49% to 72% correct at pretest to 67% to 87% correct at posttest. This study shows the feasibility of a problem-based e-learning module to help surgeons-in-training and gastroenterologists in recognizing a hereditary predisposition in patients with CRC. The e-learning led to improvements in attitude toward the assessment of cancer family history, knowledge on criteria for referral to genetic counseling for CRC, and comprehension of communication skills. ©Kirsten Freya Lea Douma, Cora M Aalfs, Evelien Dekker, Pieter J Tanis, Ellen M Smets. Originally published in JMIR Medical Education (http://mededu.jmir.org), 18.12.2017.
Lyall, Donald M; Ward, Joey; Ritchie, Stuart J; Davies, Gail; Cullen, Breda; Celis, Carlos; Bailey, Mark E S; Anderson, Jana; Evans, Jon; Mckay, Daniel F; Mcintosh, Andrew M; Sattar, Naveed; Smith, Daniel J; Deary, Ian J; Pell, Jill P
2016-07-01
the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
RELEVANCE OF PROCESS RISK ASSESSMENT IN AIRLINES
Directory of Open Access Journals (Sweden)
Oksana G. Feoktistova
2017-01-01
Full Text Available The notion of “the concept on assumed risk” that took over from the outdated concept of absolute security is analyzed, the increasing significance of operating risk assessment at the present stage is noted. Some basic risk assessment techniques are considered. Matrix technique of risk assessment is considered more thoroughly, and it may be used in risk assessment of airlines in the context of labour protection management system.The ability to correctly assess risks and develop appropriate precautionary measures will allow airlines to avoid incidents leading to drastic consequences for staff, as well as to direct and indirect costs for the enterprise among which there could be singled out both direct property damage and loss of profit and expenses connected to incident investigation, penalty and compensation payment, loss of business reputation and so on. To reduce the rate of accidents and to develop safe activities skills for airlines staff a risk assessment chart is supposed to be implemented, which will be an efficient accidents prevention involving the staff in the process and making them follow safe working conditions.Process risk assessment is an integral part of assessment of the whole enterprise activity and work efficiency of a department and particular workers evaluation system. Labour protection activity should be based on risk identification and its control. Risk assessment is a keystone of labour protection activity planning.
Wolfe, Christopher R; Reyna, Valerie F; Widmer, Colin L; Cedillos-Whynott, Elizabeth M; Brust-Renck, Priscila G; Weil, Audrey M; Hu, Xiangen
2016-07-01
The BRCA Gist Intelligent Tutoring System helps women understand and make decisions about genetic testing for breast cancer risk. BRCA Gist is guided by Fuzzy-Trace Theory, (FTT) and built using AutoTutor Lite. It responds differently to participants depending on what they say. Seven tutorial dialogues requiring explanation and argumentation are guided by three FTT concepts: forming gist explanations in one's own words, emphasizing decision-relevant information, and deliberating the consequences of decision alternatives. Participants were randomly assigned to BRCA Gist , a control, or impoverished BRCA Gist conditions removing gist explanation dialogues, argumentation dialogues, or FTT images. All BRCA Gist conditions performed significantly better than controls on knowledge, comprehension, and risk assessment. Significant differences in knowledge, comprehension, and fine-grained dialogue analyses demonstrate the efficacy of gist explanation dialogues. FTT images significantly increased knowledge. Providing more elements in arguments against testing correlated with increased knowledge and comprehension.
Llewellyn, Clare H; Fildes, Alison
2017-03-01
There is considerable variability in human body weight, despite the ubiquity of the 'obesogenic' environment. Human body weight has a strong genetic basis and it has been hypothesised that genetic susceptibility to the environment explains variation in human body weight, with differences in appetite being implicated as the mediating mechanism; so-called 'behavioural susceptibility theory' (BST), first described by Professor Jane Wardle. This review summarises the evidence for the role of appetite as a mediator of genetic risk of obesity. Variation in appetitive traits is observable from infancy, drives early weight gain and is highly heritable in infancy and childhood. Obesity-related common genetic variants identified through genome-wide association studies show associations with appetitive traits, and appetite mediates part of the observed association between genetic risk and adiposity. Obesity results from an interaction between genetic susceptibility to overeating and exposure to an 'obesogenic' food environment.