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

Chenguang Wang, Yun Cheng, Tian Liu, Qin Li, Roger B. Fillingim, Margaret R. Wallace, Roland Staud, Lee Kaplan, Rongling Wu

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article number13
JournalMolecular Pain
Volume4
DOIs
StatePublished - Apr 16 2008

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine

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