An epidemiologic approach to gene‐environment interaction

Ottman, Ruth

doi:10.1002/gepi.1370070302

Cited by 180 publications

(108 citation statements)

References 22 publications

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“…A good overview of possible causal relationships and interaction mechanisms is given by Ottman. 16 Such etiological mechanisms have to be explored by functional studies.…”

Section: Definition and Meaning Of Interactionmentioning

confidence: 99%

Gene–environment interactions for complex traits: definitions, methodological requirements and challenges

et al. 2008

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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 Â 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 Â 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 Â 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 discussed.

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“…A good overview of possible causal relationships and interaction mechanisms is given by Ottman. 16 Such etiological mechanisms have to be explored by functional studies.…”

Section: Definition and Meaning Of Interactionmentioning

confidence: 99%

Gene–environment interactions for complex traits: definitions, methodological requirements and challenges

et al. 2008

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“…Two types of models were used to simulate data under the alternative hypothesis when a gene-environment interaction is present. These models are described in Ottman (1990Ottman ( , 1996 and studied in Gauderman & Siegmund (2001) in the context of linkage tests. The first gene-environment interaction model (the pure interaction model) assumes that the risk of becoming affected is a function of the product of the numerical coding of the genotype and the environmental exposure and does not depend on main effects of the gene or environmental exposure.…”

Section: Design Of Simulationsmentioning

confidence: 99%

Tests of Gene‐Environment Interaction for Case‐Parent Triads with General Environmental Exposures

Lake

Laird

2004

Annals of Human Genetics

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SummaryAs knowledge of the human genome continues to grow, more progress is being made towards not only identifying the genes involved in disease susceptibility but also in defining the synergistic role genes play with environmental exposures. The detection of gene-environment interactions is important as it can offer clinicians a potential means of intervention. The discovery of interactions relies heavily on powerful statistical methods. We present a test, FBAT-I, that can be used to investigate gene-environment interaction. The test uses the case-parent triad design and protects the statistical inference from potential spurious results due to population admixture.

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“…This information improved the likelihood of detecting effects of these indicators. 10,11 For example, the indicator variable about daily smoking for the adoptee and for the biological relative was combined as follows: 1) both non-smokers; 2) mixed group, with either the adoptee or the biological relative being smokers and 3) both smokers. Similar combinations were constructed for year of birth and occupational rating.…”

Section: Strategy Of Analysismentioning

confidence: 99%

Adoption study of environmental modifications of the genetic influences on obesity

1997

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BACKGROUND: Adult body mass index (BMI weight (kg)aheight 2 (m 2 )) usually shows familial correlations below 0.3, which are almost entirely due to genetic in¯uences. The considerable remaining non-familial individual variation may be due to non-shared environmental in¯uences which, however, may interact with or modify the genetic in¯uence. OBJECTIVE: To investigate whether the genetic in¯uence on adult BMI is modi®ed by various obesity-related environmental conditions during childhood and adulthood. DESIGN: Adoption study, in which the genetic in¯uence is assessed by the correlations in adult BMI between adoptees and their biological fathers, mothers and full siblings. These correlations were compared between groups of families characterized by differences in rearing or adult environment of the adoptees and/or their biological relatives. SUBJECTS: Height, current weight and greatest weight ever, were obtained in 3651 subjects, who were adopted by non-related families in Copenhagen between 1924 and 1947. Groups representing thin, medium weight, overweight and obese proband adoptees were selected by current BMI (n 540) and by maximum BMI (n 524). The members of the biological and adoptive families of the proband adoptees were identi®ed and their BMI was computed from height and weight obtained by mailed questionnaires. MAIN VARIABLES: Indicators related to the rearing environment of the adoptees were age of the adoptee at transfer to the adoptive family, region of residence, presence of adoptive siblings and, for the adoptive parents, year of birth, age at time of adoption, occupational rating, smoking habits and BMI. Indicators of the environment of both the adoptee and the biological relatives were: year of birth; occupational rating and smoking habits, and, of the environment of the biological parents, age and parity at birth of the adoptee. RESULTS: The correlations in BMI between adoptees and the biological fathers, mothers and siblings were 0.11, 0.15 and 0.26 for adoptees selected by current BMI, and 0.13, 0.16, and 0.27 for adoptees selected by maximum BMI, respectively (all P`0.001), demonstrating the previously reported genetic in¯uence. None of the environmental indicators showed consistent and signi®cant effects on these six correlations. The same negative results were obtained in analysis of environmental indicators applied to the two adoptive parents together or to the adoptee and the biological relatives together. CONCLUSION: The genetic in¯uence on BMI was unaffected by several different environmental conditions otherwise associated with obesity.

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An epidemiologic approach to gene‐environment interaction

Cited by 180 publications

References 22 publications

Gene–environment interactions for complex traits: definitions, methodological requirements and challenges

Gene–environment interactions for complex traits: definitions, methodological requirements and challenges

Tests of Gene‐Environment Interaction for Case‐Parent Triads with General Environmental Exposures

Adoption study of environmental modifications of the genetic influences on obesity

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