Uncovering hidden variance: pair-wise SNP analysis accounts for additional variance in nicotine dependence.

ABSTRACT: Results from genome-wide association studies of complex traits account for only a modest proportion of the trait variance predicted to be due to genetics. We hypothesize that joint analysis of polymorphisms may account for more variance. We evaluated this hypothesis on a case-control smoking phenotype by examining pairs of nicotinic receptor single-nucleotide polymorphisms (SNPs) using the Restricted Partition Method (RPM) on data from the Collaborative Genetic Study of Nicotine Dependence (COGEND). We found evidence of joint effects that increase explained variance. Four signals identified in COGEND were testable in independent American Cancer Society (ACS) data, and three of the four signals replicated. Our results highlight two important lessons: joint effects that increase the explaine

SUBMITTER: Culverhouse RC 

PROVIDER: S-EPMC3030551 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature