Obesity Epidemiology

464 EPIDEMIOLOGIC STUDIES OF DETERMINANTS OF OBESITYTable 22.1 Layouts for a Case-Control Study Assessing the Effect of a Genotype and anEnvironmental FactorG* E* Cases Controls Odds Ratio Contrast Main Information+ + a b ah/bg A A vs. D Joint genotype andenvironmentalfactor vs. none+ – c d ch/dg B B vs. D Genotype alone vs.none– + e f eh/fg C C vs. D Environmentalfactor alone vs.none– – g h 1 D Common referenceOther Measures Odds Ratio Main InformationCase-only odds ratio ag/ce Departure from multiplicative model ofinteractionControl only odds ratio bh/df Independence of factors in the populationMultiplicativeinteractionA(B × C)Deviation from multiplicative model ofinteractionAdditive interaction A – (B + C – 1) Deviation from additive model ofinteractionReproduced with permission from Botto LD, Khoury MJ. Commentary: facing the challenge of gene-environment interaction:the two-by-four table and beyond. Am J Epidemiol. 2001;153:1016-1020. 16ORs for exposure to each individual factor) can be evaluated using the likelihood ratiotest (Chapter 4).Departure from additivity can be evaluated by the synergy index, S (see Chapter 4).S and its corresponding confidence interval can be calculated by using estimated OR andcovariances derived from logistic regression models. 18 S > 1 indicates departure fromadditive effects of the gene and environmental factors. Another measure, relative excessrisk due to interaction (RERI), has also been used to assess additive interactions. 19Study Designs for Evaluating Gene-Environment InteractionsObservational association studies and randomized clinical trials are two main typesof study designs for testing the effects of gene-environment interactions on obesity(Table 22.2). Association studies are conducted either in families or in unrelated individuals.There are two main types of family-based association studies: case-parent trioand affected relative pair; 20 both can be used to evaluate gene-environment interactions.The case-parent trio design uses the parents of case subjects as controls, and ORs of thegenotype are calculated according to strata of an environmental exposure, thus allowingestimation of gene-environment interactions. The advantage of such a design is immunityto population stratification bias. However, it can be difficult to implement because of difficultyin collecting DNA samples from parents, especially for late onset disease. 21 Also,family-based studies generally have less power than case-control studies of unrelated individualswith the same number of subjects. The affected relative pair study, also knownas the affected sibpair method, allows researchers to assess linkage between a locus anddisease as well as departure from multiplicative effects of environmental and genetic factors.However, it cannot assess the effects of either exposure or specific alleles. 20