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A computational model for sex-specific genetic architecture of complex traits in humans: Implications for mapping pain sensitivity

Author(s): Wang Chenguang | Cheng Yun | Liu Tian | Li Qin | Fillingim Roger | Wallace Margaret | Staud Roland | Kaplan Lee | Wu Rongling

Journal: Molecular Pain
ISSN 1744-8069

Volume: 4;
Issue: 1;
Start page: 13;
Date: 2008;
Original page

Abstract Understanding differences in the genetic architecture of complex traits between the two sexes has significant implications for evolutionary studies and clinical diagnosis. However, our knowledge about sex-specific genetic architecture is limited largely because of a lack of analytical models that can detect and quantify the effects of sex on the complexity of quantitative genetic variation. Here, we derived a statistical model for mapping DNA sequence variants that contribute to sex-specific differences in allele frequencies, linkage disequilibria, and additive and dominance genetic effects due to haplotype diversity. This model allows a genome-wide search for functional haplotypes and the estimation and test of haplotype by sex interactions and sex-specific heritability. The model, validated by simulation studies, was used to detect sex-specific functional haplotypes that encode a pain sensitivity trait in humans. The model could have important implications for mapping complex trait genes and studying the detailed genetic architecture of sex-specific differences.

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Tango Rapperswil

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