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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Social, Behavioral, and Genetic Linkages from Adolescence Into Adulthood
Kathleen Mullan Harris,Carolyn Tucker Halpern,Jon M. Hussey,Eric A. Whitsel,Ley A. Killeya-Jones,Joyce W. Tabor,Glen H. Elder,John K. Hewitt,Michael J. Shanahan,Redford B. Williams,Ilene C. Siegler,Andrew Smolen +11 more
TL;DR: This work describes the Add Health study as an exemplar to illustrate approaches to understanding health through investigation of the interplay among biological, psychosocial, and physical, contextual, or cultural experiences.
Journal ArticleDOI
Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development
Harriet Cullen,Michelle L. Krishnan,Michelle L. Krishnan,Saskia Selzam,Gareth Ball,Alessia Visconti,Alka Saxena,Serena J. Counsell,Jo Hajnal,Gerome Breen,Gerome Breen,Robert Plomin,A. David Edwards +12 more
TL;DR: Deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness and genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress.
Journal ArticleDOI
Gene-environment interactions in cardiovascular disease
TL;DR: Theoretical underpinnings of gene–environment interactions, models of interaction, methods for studying gene– Environment interactions, and the related concept of interactions between epigenetic mechanisms and the environment are described.
Journal ArticleDOI
Serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on adulthood social attachment.
TL;DR: This work examined whether the T102C variant of the serotonin receptor 2A gene moderates the effect of childhood maternal nurturance on social attachment in adulthood and suggested that T/T genotype carriers were more influenced by their childhood nurturing environment than their C allele carrying counterparts.
Journal ArticleDOI
A gene–environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactive disorder
Christian Jacob,Thuy Trang Nguyen,Astrid Dempfle,Monika Heine,Christine Windemuth-Kieselbach,Katarina Baumann,Florian Jacob,Julian Prechtl,Maike Wittlich,Martin J. Herrmann,Silke Gross-Lesch,Klaus-Peter Lesch,Andreas Reif +12 more
TL;DR: Main effects as well as main effects of 5-HTT-LPR and the TPH2 SNP rs4570625 on the occurrence of personality disorders are observed and a G × E interaction term is taken into account, since this approach may better fit the data indicating that the effect of a gene is modified by stressful life events or, vice versa, that stressfulLife events only have an effect in the presence of a susceptibility genotype.
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