TY - JOUR
T1 - A computational model for sex-specific genetic architecture of complex traits in humans
T2 - Implications for mapping pain sensitivity
AU - Wang, Chenguang
AU - Cheng, Yun
AU - Liu, Tian
AU - Li, Qin
AU - Fillingim, Roger B.
AU - Wallace, Margaret R.
AU - Staud, Roland
AU - Kaplan, Lee
AU - Wu, Rongling
PY - 2008/4/16
Y1 - 2008/4/16
N2 - 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.
AB - 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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U2 - 10.1186/1744-8069-4-13
DO - 10.1186/1744-8069-4-13
M3 - Article
C2 - 18416828
AN - SCOPUS:44949217429
SN - 1744-8069
VL - 4
JO - Molecular Pain
JF - Molecular Pain
M1 - 13
ER -