Allelic-based gene-gene interaction associated with quantitative traits

Jeesun Jung, Bin Sun, Deukwoo Kwon, Daniel L. Koller, Tatiana M. Foroud

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)332-343
Number of pages12
JournalGenetic epidemiology
Volume33
Issue number4
DOIs
StatePublished - 2009

Keywords

  • Allelic test
  • Blood pressure
  • Interaction effect
  • Quantitative trait loci

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

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