Title | Studying gene and gene-environment effects of uncommon and common variants on continuous traits: a marker-set approach using gene-trait similarity regression. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Tzeng, Jung-Ying, Daowen Zhang, Monnat Pongpanich, Chris Smith, Mark I. McCarthy, Michèle M. Sale, Bradford B. Worrall, Fang-Chi Hsu, Duncan C. Thomas, and Patrick F. Sullivan |
Journal | Am J Hum Genet |
Volume | 89 |
Issue | 2 |
Pagination | 277-88 |
Date Published | 2011 Aug 12 |
ISSN | 1537-6605 |
Keywords | Chromosomes, Human, Pair 21, Computer Simulation, Databases, Genetic, Environment, Genes, Genetic Markers, Humans, Models, Genetic, Mutation, Quantitative Trait, Heritable, Regression Analysis |
Abstract | Genomic association analyses of complex traits demand statistical tools that are capable of detecting small effects of common and rare variants and modeling complex interaction effects and yet are computationally feasible. In this work, we introduce a similarity-based regression method for assessing the main genetic and interaction effects of a group of markers on quantitative traits. The method uses genetic similarity to aggregate information from multiple polymorphic sites and integrates adaptive weights that depend on allele frequencies to accomodate common and uncommon variants. Collapsing information at the similarity level instead of the genotype level avoids canceling signals that have the opposite etiological effects and is applicable to any class of genetic variants without the need for dichotomizing the allele types. To assess gene-trait associations, we regress trait similarities for pairs of unrelated individuals on their genetic similarities and assess association by using a score test whose limiting distribution is derived in this work. The proposed regression framework allows for covariates, has the capacity to model both main and interaction effects, can be applied to a mixture of different polymorphism types, and is computationally efficient. These features make it an ideal tool for evaluating associations between phenotype and marker sets defined by linkage disequilibrium (LD) blocks, genes, or pathways in whole-genome analysis. |
DOI | 10.1016/j.ajhg.2011.07.007 |
Alternate Journal | Am J Hum Genet |
Original Publication | Studying gene and gene-environment effects of uncommon and common variants on continuous traits: a marker-set approach using gene-trait similarity regression. |
PubMed ID | 21835306 |
PubMed Central ID | PMC3155192 |
Grant List | R01 CA85848 / CA / NCI NIH HHS / United States R01 MH084022 / MH / NIMH NIH HHS / United States R01 MH084022-02 / MH / NIMH NIH HHS / United States R01 CA085848 / CA / NCI NIH HHS / United States R01 ES019876 / ES / NIEHS NIH HHS / United States M01 RR007122 / RR / NCRR NIH HHS / United States P01 CA142538 / CA / NCI NIH HHS / United States R01 MH084022-01A1 / MH / NIMH NIH HHS / United States R01 MH074027 / MH / NIMH NIH HHS / United States U01 HG005160 / HG / NHGRI NIH HHS / United States 090532 / / Wellcome Trust / United Kingdom R01 MH084022-03 / MH / NIMH NIH HHS / United States R37 AI031789-20 / AI / NIAID NIH HHS / United States R37 AI031789 / AI / NIAID NIH HHS / United States M01 RR07122 / RR / NCRR NIH HHS / United States |
Studying gene and gene-environment effects of uncommon and common variants on continuous traits: a marker-set approach using gene-trait similarity regression.
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