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Comparison of the power of haplotype-based versus single- and multilocus association methods for gene × environment (gene × sex) interactions and application to gene × smoking and gene × sex interactions in rheumatoid arthritis

By Astrid Dempfle, Rebecca Hein, Lars Beckmann, André Scherag, Thuy Trang Nguyen, Helmut Schäfer and Jenny Chang-Claude

Abstract

Accounting for interactions with environmental factors in association studies may improve the power to detect genetic effects and may help identifying important environmental effect modifiers. The power of unphased genotype-versus haplotype-based methods in regions with high linkage disequilibrium (LD), as measured by D', for analyzing gene × environment (gene × sex) interactions was compared using the Genetic Analysis Workshop 15 (GAW15) simulated data on rheumatoid arthritis with prior knowledge of the answers. Stepwise and regular conditional logistic regression (CLR) was performed using a matched case-control sample for a HLA region interacting with sex. Haplotype-based analyses were performed using a haplotype-sharing-based Mantel statistic and a test for haplotype-trait association in a general linear model framework. A step-down minP algorithm was applied to derive adjusted p-values and to allow for power comparisons. These methods were also applied to the GAW15 real data set for PTPN22

Topics: Proceedings
Publisher: BioMed Central
OAI identifier: oai:pubmedcentral.nih.gov:2367597
Provided by: PubMed Central

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