Thursday, October 2, 2014

Sex differences in human disease genetics

Trends in Genetics' lovely image accompanying our paper.

Posted by Jessica Abbott

Just wanted to write a short post highlighting my new paper with Will Gilks and Ted Morrow. It's a review of the evidence for sex-specific genetic effects on disease risk in humans. However we also discuss the evolutionary origins of such sex-specific differences in genetic architecture, which we suggest is a result of the resolution of sexually antagonistic selection pressures.

I'm very happy to see this paper published, for a couple of reasons. For one thing, this review is something that Ted and I talked about for a long time, so it's great to see how it's taken shape. Will's expertise in human genetics and GWAS contributed a lot to the final product. For another, it seems to have been very timely, since the NIH in the United States just announced over 10 million USD in new funding to include sex and gender differences in ongoing clinical research. Publishing in a "proper" genetics journal such as Trends in Genetics also raises my profile an evolutionary geneticist, I think.

Check it out!

Gilks, W. P., Abbott, J. K., & Morrow, E. H. (2014) Sex differences in disease genetics: evidence, evolution and detection. Trends in Genetics, 30(10):453-463.

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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