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Sex differences in disease genetics

journal contribution
posted on 2023-06-09, 03:58 authored by William P Gilks
There is long-standing evidence for the gene-by-sex interactions in disease risk, which can now be tested in genome-wide association studies with participant numbers in the hundreds of thousands. The current methods start with a separate test for each sex, but a more powerful approach is to use sex as an interaction term in a combined sample. The most compelling evidence is for adiposity (predictive of cardiac disease) as well as type II diabetes, asthma and inflammatory bowel disease. Autism exhibits a different kind of sex difference, with hypermasculinisation of the brain, and the intriguing enrichment of structural variants in females. Sexually dimorphic gene expression varies exquisitely and unexpectedly, by tissue, age and chromosome, so sex-dependent genetic effects are expected for a wide range of diseases. Because natural selection against sex-dependent risk alleles is in one sex only, their effect size is expected to be greater than conventional risk loci.

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

eLS

ISSN

1618-0240

Publisher

Wiley

Volume

0

Page range

1-7

Department affiliated with

  • Evolution, Behaviour and Environment Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2016-11-09

First Compliant Deposit (FCD) Date

2016-11-09

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