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Allelic‐based gene‐gene interaction associated with quantitative traits
Author(s) -
Jung Jeesun,
Sun Bin,
Kwon Deukwoo,
Koller Daniel L.,
Foroud Tatiana M.
Publication year - 2009
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20385
Subject(s) - genetics , quantitative trait locus , allele , single nucleotide polymorphism , biology , gene , allelic heterogeneity , genetic association , genotype , gene interaction , phenotype , computational biology
Recent studies have shown that quantitative phenotypes may be influenced not only by multiple single nucleotide polymorphisms (SNPs) within a gene but also by the interaction between SNPs at unlinked genes. We propose a new statistical approach that can detect gene‐gene interactions at the allelic level which contribute to the phenotypic variation in a quantitative trait. By testing for the association of allelic combinations at multiple unlinked loci with a quantitative trait, we can detect the SNP allelic interaction whether or not it can be detected as a main effect. Our proposed method assigns a score to unrelated subjects according to their allelic combination inferred from observed genotypes at two or more unlinked SNPs, and then tests for the association of the allelic score with a quantitative trait. To investigate the statistical properties of the proposed method, we performed a simulation study to estimate type I error rates and power and demonstrated that this allelic approach achieves greater power than the more commonly used genotypic approach to test for gene‐gene interaction. As an example, the proposed method was applied to data obtained as part of a candidate gene study of sodium retention by the kidney. We found that this method detects an interaction between the calcium‐sensing receptor gene ( CaSR ), the chloride channel gene ( CLCNKB ) and the Na, K, 2Cl cotransporter gene ( CLC12A1 ) that contributes to variation in diastolic blood pressure. Genet. Epidemiol . 2009. © 2008 Wiley‐Liss, Inc.