title: A computational model for sex-specific genetic architecture of complex traits in humans: implications for mapping pain sensitivity.
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.
authors.affiliation: Department of Statistics, University of Florida, Gainesville, FL 32611 USA. cgwang@cog.ufl.edu
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Cheng
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Roger B
authors.initials: RB
authors.lastname: Fillingim
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wallace
authors.forename: Roland
authors.initials: R
authors.lastname: Staud
authors.forename: Lee
authors.initials: L
authors.lastname: Kaplan
authors.forename: Rongling
authors.initials: R
authors.lastname: Wu
mesh_terms: D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D017288:Pain Threshold; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012727:Sex Characteristics