title: Heritability estimation of sex-specific effects on human quantitative traits.
abstract: Recent studies have suggested that sex-specific genetic architecture could be because of the effects of autosomal genes that are differentially expressed in males and females. Yet, few studies have explored the effects of X-linked genes on sex-specific genetic architecture. In this study, we extended the variance component, maximum likelihood method to evaluate the relative contributions of sex-specific effects on both autosomes and the X chromosome to estimates of heritability of 20 quantitative human phenotypes in the Hutterites. Seventeen of these traits were previously analyzed in this population under a model that did not include X chromosomal effects; three traits are analyzed for the first time (age at menarche, percent fat and fat-free mass [FFM]). Seven traits (systolic blood pressure (SBP), adult height, fasting insulin, triglycerides, lipoprotein (a) [Lp(a)], serotonin, and age at menarche) showed significant X-linked effects; three of these (SBP, adult height, and triglycerides) showed X-linked effects only in males. Four traits (Lp(a), low-density lipoprotein cholesterol, ratio of percent predicted forced expiratory volume at 1 s/forced vital capacity, and FFM) showed significant sex-environment interactions, and two traits (high-density lipoprotein cholesterol and FFM) showed significant sex-specific autosomal effects. Our analyses demonstrate that sex-specific genetic effects may not only be common in human quantitative traits, but also that the X chromosome both plays a large role in these effects and has a variable influence between the sexes.
authors.affiliation: Department of Human Genetics, The University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: Mark
authors.initials: M
authors.lastname: Abney
mesh_terms: D000328:Adult; D041321:Chromosomes, Human, X; D005260:Female; D018703:Founder Effect; D050172:Genes, X-Linked; D006801:Humans; D008297:Male; D008957:Models, Genetic; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012727:Sex Characteristics; D013023:South Dakota