title: Sex differences in disease genetics: evidence, evolution, and detection.
abstract: Understanding the genetic architecture of disease is an enormous challenge, and should be guided by evolutionary principles. Recent studies in evolutionary genetics show that sexual selection can have a profound influence on the genetic architecture of complex traits. Here, we summarise data from heritability studies and genome-wide association studies (GWASs) showing that common genetic variation influences many diseases and medically relevant traits in a sex-dependent manner. In addition, we discuss how the discovery of sex-dependent effects in population samples is improved by joint interaction analysis (rather than separate-sex), as well as by recently developed software. Finally, we argue that although genetic variation that has sex-dependent effects on disease risk could be maintained by mutation-selection balance and genetic drift, recent evidence indicates that intra-locus sexual conflict could be a powerful influence on complex trait architecture, and maintain sex-dependent disease risk alleles in a population because they are beneficial to the opposite sex.
authors.affiliation: Evolution, Behaviour, and Environment Group, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK. Electronic address: w.gilks@sussex.ac.uk.
authors.forename: William P
authors.initials: WP
authors.lastname: Gilks
authors.affiliation: Experimental Evolution, Ecology, and Behaviour Group, Department of Biology, Section for Evolutionary Ecology, Lund University, Sölvegatan 37, 22362 Lund, Sweden.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Abbott
authors.affiliation: Evolution, Behaviour, and Environment Group, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Morrow
mesh_terms: D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D058685:Genetic Pleiotropy; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D012737:Sex Factors
keywords: GWAS; GxS; complex trait; disease; intra-locus sexual conflict; sexual selection