• Chenguang Wang, Yun Cheng, Tian Liu, Qin Li, Roger B Fillingim, Margaret R Wallace, Roland Staud, Lee Kaplan, and Rongling Wu.
• Department of Statistics, University of Florida, Gainesville, FL 32611 USA. cgwang@cog.ufl.edu
• Mol Pain. 2008 Apr 16; 4: 13.

AbstractUnderstanding 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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