The case-only independence assumption: associations between genetic polymorphisms and smoking among controls in two population-based studies

International Journal of Molecular Epidemiology and Genetics

Kari E North¹  M Elizabeth Hodgson¹  Tope O Keku¹  Chiu-Kit Tse¹  Andrew F Olshan¹  Robert C Millikan¹  Donglin Zeng¹  Charles L Poole¹  Joseph Galanko¹  Robert Sandler¹ 

关键词: Case-only;    controls;    gene-environment interaction;    genetic polymorphisms;    smoking;   

DOI  :  

学科分类：流行病学

来源: e-Century Publishing Corporation

【 摘 要 】

The independence assumption for a case-only analysis of statistical interaction, i. e. that genetic (G) and environmental exposures (E) are not associated in the source population, is often checked in surrogate populations. Few studies have examined G-E association in empirical data, particularly in controls from population-based studies, the type of controls expected to provide the most valid surrogate estimates of G-E association. We used controls from two population-based case-control studies to evaluate G-E independence for 43 selected genetic polymorphisms and smoking behavior. The odds ratio (OR_z) was used to estimate G-E association and, therefore, the magnitude of bias introduced into the case-only odds ratio (COR). Odds ratios of moderate magnitude [mmOR_z], defined as OR_z≤0.7 or OR_z≥1.4, were found at least one of the six smoking measures (ever, former, current, cig/day, years smoked, pack-years) for 45% and 59% of the SNPs examined in the control groups of two independently conducted North Carolina studies, respectively. Consequently, case-only estimates of G-E interaction in the context of a multiplicative benchmark would be biased for these SNPs and smoking measures. MmOR_zs were found more often for smoking amount than smoking status. We recommend that a stand-alone case-only study should only be conducted when G-E independence can be verified for each polymorphism and exposure metric with population-specific data. Our results suggest that OR_z is specific to each underlying population rather than an estimate of a ‘universal’ OR_z for that SNP and smoking measure. Further, misspecification of smoking is likely to introduce bias into the COR.

【 授权许可】

Unknown