Journal
TRENDS IN GENETICS
Volume 30, Issue 10, Pages 453-463Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tig.2014.08.006
Keywords
intra-locus sexual conflict; GWAS; sexual selection; GxS; complex trait; disease
Categories
Funding
- European Research Council [280632]
- Royal Society University Research Fellowship
- Swedish Research Council
- Volkswagen Foundation
- European Research Council (ERC) [280632] Funding Source: European Research Council (ERC)
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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 intralocus 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.
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