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- Gilks, William P, et al.
(author)
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Sex differences in disease genetics: evidence, evolution, and detection.
- 2014
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In: Trends in Genetics. - : Elsevier BV. - 1362-4555 .- 0168-9525. ; 30:10, s. 453-463
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Research review (peer-reviewed)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.
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