Evolution, Behaviour, and Environment Group, School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
Experimental Evolution, Ecology, and Behaviour Group, Department of Biology, Section for Evolutionary Ecology, Lund University, Sölvegatan 37, 22362 Lund, Sweden.
Trends Genet. 2014 Oct;30(10):453-63. doi: 10.1016/j.tig.2014.08.006. Epub 2014 Sep 16.
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.
理解疾病的遗传结构是一个巨大的挑战，应该以进化原则为指导。进化遗传学的最新研究表明，性选择可以对复杂性状的遗传结构产生深远影响。在这里，我们总结了来自遗传力研究和全基因组关联研究（GWAS）的数据，表明常见的遗传变异以性别依赖的方式影响许多疾病和与医学相关的特征。此外，我们还讨论了如何通过联合相互作用分析（而不是单独的性别分析）以及最近开发的软件来提高在群体样本中发现性别相关效应的能力。最后，我们认为，尽管对疾病风险具有性别依赖性影响的遗传变异可以通过突变-选择平衡和遗传漂变来维持，但最近的证据表明，基因内的性冲突可能是对复杂性状结构产生强大影响的因素，并在种群中维持性别相关的疾病风险等位基因，因为它们对异性有利。
