Gene-environment interactions for complex traits: Definitions, methodological requirements and challenges
Astrid Dempfle,André Scherag,André Scherag,Rebecca Hein,Lars Beckmann,Jenny Chang-Claude,Helmut Schäfer +6 more
TLDR
This review discusses methodological issues involved in investigating gene–environment (G × E) interactions in genetic–epidemiological studies of complex diseases and their potential relevance for clinical application and attempts to clarify conceptual differences of the term ‘interaction’ in the statistical and biological sciences.Abstract:
Genetic and environmental risk factors and their interactions contribute to the development of complex diseases In this review, we discuss methodological issues involved in investigating gene-environment (G x E) interactions in genetic-epidemiological studies of complex diseases and their potential relevance for clinical application Although there are some important examples of interactions and applications, the widespread use of the knowledge about G x E interaction for targeted intervention or personalized treatment (pharmacogenetics) is still beyond current means This is due to the fact that convincing evidence and high predictive or discriminative power are necessary conditions for usefulness in clinical practice We attempt to clarify conceptual differences of the term 'interaction' in the statistical and biological sciences, since precise definitions are important for the interpretation of results We argue that the investigation of G x E interactions is more rewarding for the detailed characterization of identified disease genes (ie at advanced stages of genetic research) and the stratified analysis of environmental effects by genotype or vice versa Advantages and disadvantages of different epidemiological study designs are given and sample size requirements are exemplified These issues as well as a critical appraisal of common methodological concerns are finally discussedread more
Citations
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Unravelling the complex genetics of common kidney diseases: from variants to mechanisms
TL;DR: The authors propose that identification of causal variants, genetic regulatory mechanisms, target-gene products and disease-associated phenotypes is crucial to this process and the use of advanced computational approaches to combine datasets orthogonal to GWAS data, including molecular quantitative trait studies, single-cell transcriptomics and epigenetic information, is necessary for the prioritization of GWAS variants.
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Environmental exposures to metals in Native communities and implications for child development: basis for the Navajo birth cohort study.
Johnnye Lewis,Melissa Gonzales,Courtney P. Burnette,Malcolm Benally,Paula Seanez,Christopher Shuey,Helen Nez,Christopher Nez,Seraphina Nez +8 more
TL;DR: Concern has emerged among tribal populations that metals exposure from abandoned mines might threaten development of future generations.
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Genetically modulated educational attainment and coronary disease risk.
Lingyao Zeng,Ioanna Ntalla,Thorsten Kessler,Adnan Kastrati,Jeanette Erdmann,John Danesh,John Danesh,Hugh Watkins,Hugh Watkins,Nilesh J. Samani,Nilesh J. Samani,Panos Deloukas,Panos Deloukas,Heribert Schunkert +13 more
TL;DR: In contrast, a model adjusting for BMI and smoking abolished the association signal between the 'genetic education score' and CAD risk suggesting an intermediary role of these two risk factors.
A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder Christian P. JacobThuy Trang NguyenAstrid DempfleMonika HeineChristine Windemuth-Kieselbach • Katarina BaumannFlorian JacobJulian PrechtlMaike WittlichMartin J. Herrmann • Silke Gross-LeschKlaus-Peter LeschAndreas Reif
C. P. Jacob,Monika Heine,K. Baumann,F. Jacob,J. Prechtl,M. Wittlich,M. J. Herrmann,Silke Gross-Lesch,P. Lesch,A. Reif,T. T. Nguyen,Astrid Dempfle,Christine Windemuth-Kieselbach +12 more
TL;DR: In this article, the effect of genes with adverse life events (e.g., stressors) on personality and related disorders was investigated in two independent samples consisting of 183 patients suffering from person-ality disorders and 123 patients with adult attention deficit/hyperactivity disorder (aADHD).
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Polymorphisms in the Caspase Genes and the Risk of Lung Cancer
Shin Yup Lee,Yi Young Choi,Jin Eun Choi,Min Jung Kim,Jongsik Kim,Deuk Kju Jung,Hyo-Gyoung Kang,Hyo-Sung Jeon,Won Kee Lee,Guang Jin,Guang Jin,Seung Ick Cha,Chang Ho Kim,Tae Hoon Jung,Jae Yong Park,Jae Yong Park +15 more
TL;DR: A combined analysis of these three CASP gene polymorphisms might better predict the risk of lung cancer than analysis of a single polymorphism.
References
More filters
Journal ArticleDOI
‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?
George Davey Smith,Shah Ebrahim +1 more
TL;DR: Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.
Journal ArticleDOI
Sick individuals and sick populations
TL;DR: Aetiology confronts two distinct issues: the determinant of individual cases, and the determinants of incidence rate: if exposure to a necessary agent is homogeneous within a population, then case/control and cohort methods will fail to detect it.
Journal ArticleDOI
Replication validity of genetic association studies.
John P. A. Ioannidis,Evangelia E. Ntzani,Thomas A Trikalinos,Despina G. Contopoulos-Ioannidis,Despina G. Contopoulos-Ioannidis +4 more
TL;DR: It is concluded that a systematic meta-analytic approach may assist in estimating population-wide effects of genetic risk factors in human disease.
Journal ArticleDOI
European prospective investigation into cancer and nutrition (EPIC): study populations and data collection
Elio Riboli,Kelly J. Hunt,Nadia Slimani,Pietro Ferrari,Teresa Norat,Michael T. Fahey,Charrondière Ur,Bertrand Hémon,Corinne Casagrande,Jérôme Vignat,Kim Overvad,Anne Tjønneland,Françoise Clavel-Chapelon,Anne C. M. Thiébaut,Jürgen Wahrendorf,Heiner Boeing,Dimitrios Trichopoulos,Dimitrios Trichopoulos,Antonia Trichopoulou,Paolo Vineis,Domenico Palli,H. B. Bueno-De-Mesquita,Petra H.M. Peeters,Eiliv Lund,Dagrun Engeset,Carlos A. González,Aurelio Barricarte,Göran Berglund,Göran Hallmans,Nicholas E. Day,Timothy J. Key,Rudolf Kaaks,R. Saracci +32 more
TL;DR: The present paper provides a description of theEPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
Journal ArticleDOI
Epistasis: what it means, what it doesn't mean, and statistical methods to detect it in humans
TL;DR: It is noted that the degree to which statistical tests of epistasis can elucidate underlying biological interactions may be more limited than previously assumed.
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