File(s) under permanent embargo
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 MorrowUnderstanding 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 GeneticsISSN
0168-9525Publisher
Elsevier (Cell Press)External DOI
Issue
10Volume
30Page range
453-463Department affiliated with
- Evolution, Behaviour and Environment Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2014-11-04First Compliant Deposit (FCD) Date
2014-11-04Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC