Sexually antagonistic selection, occurring when a version of a trait is advantageous to one sex but detrimental to the other, is at the origin of biological differences between the sexes. Despite their significance in shaping genetic diversity, the specific genetic loci evolving under sexually antagonistic selection are unknown and their implications in phenotypic variations in humans remain largely unexplored. Yet, differences in disease incidence between the sexes, such as the higher rates of cardiovascular diseases in men and autoimmune disorders in women, may reflect underlying sexually antagonistic dynamics. This project aims at investigating a genomic signature of sexually antagonistic selection: sex-biased transmission distortion within parents-child duos or trios. We previously developed a method (Lucotte et al. 2022) that allows to discriminate between different types of sex-biased selection, and to extract genomic regions specifically undergoing sexually antagonistic selection by identify sex-biased transmission distortion within parents-child trios or duos. Having access to the UK Biobank dataset will provide unprecedented power, because it includes genetic and medical data from 897 trios. We will identify genomic regions undergoing sex-biased transmission distortion and determine when transmission distortion takes place during the life cycle, by distinguishing alleles transmitted by the mother and the father thanks to a recent unpublished method development. Then, we will correlate these genomic signatures with phenotypic data present in the UK Biobank, focusing on sex-biased diseases and complications during pregnancy. We will also investigate specific phenotypes thought to be evolving under sexually antagonistic selection, such as adult height. This project seeks to uncover the genetic bases of phenotype variations between the sexes, including diseases with sex-biased incidence and infertility.
