Methodology

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

Chenguang Wang¹ , Yun Cheng¹ , Tian Liu¹ , Qin Li¹ , Roger B Fillingim² , Margaret R Wallace³ , Roland Staud³ , Lee Kaplan³ and Rongling Wu¹

¹  Department of Statistics, University of Florida, Gainesville, FL 32611 USA

²  Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville, FL 32611, USA

³  Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611, USA

author email corresponding author email

Molecular Pain 2008, 4:13doi:10.1186/1744-8069-4-13

Published:	16 April 2008

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.