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Sex differences in disease genetics: evidence, evolution, and detection

journal contribution
posted on 2023-06-08, 18:51 authored by William P Gilks, Jessica K Abbott, Ted Morrow
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.

Funding

2Sexes_1Genome: Sex-specific genetic effects on fitness and human disease; G0781; EUROPEAN UNION; 2011-STG280632

History

Publication status

  • Published

File Version

  • Published version

Journal

Trends in Genetics

ISSN

0168-9525

Publisher

Elsevier (Cell Press)

Issue

10

Volume

30

Page range

453-463

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2014-11-04

First Compliant Deposit (FCD) Date

2014-11-04

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