英国爱丁堡大学Albert Tenesa团队揭示英国生物银行中遗传结构的性别差异。该研究于2021年9月7日发表于国际一流学术期刊《自然—遗传学》。

研究人员对基因型与性别（GxS）的范围和机制进行了深入研究，这涉及到英国生物库中大约45万名具有欧洲血统的个体和530个复杂特征的基因组。研究人员发现不同性状的遗传结构有微小而广泛的差异。研究人员还发现，在某些情况下，性别诊断分析可能会遗漏与性状相关的位点，并研究了在预测高水平表型方面可能的改进。

最后，研究人员揭示了通过性别偏向的基因表达和基因水平分析观察到的差异的潜在功能作用。这些结果表明，在未来的研究中需要考虑性别相关的分析，从而阐明可能的性别特异性分子机制。

据介绍，男性和女性在复杂的性状和各种疾病的风险方面存在差异。GxS的相互作用被认为是这些差异的一部分原因。然而，人们对GxS的程度和基础了解甚少。

附：英文原文

Title: Sex differences in genetic architecture in the UK Biobank

Author: Bernabeu, Elena, Canela-Xandri, Oriol, Rawlik, Konrad, Talenti, Andrea, Prendergast, James, Tenesa, Albert

Issue&Volume: 2021-09-07

Abstract: Males and females present differences in complex traits and in the risk of a wide array of diseases. Genotype by sex (GxS) interactions are thought to account for some of these differences. However, the extent and basis of GxS are poorly understood. In the present study, we provide insights into both the scope and the mechanism of GxS across the genome of about 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits. We also found that, in some cases, sex-agnostic analyses may be missing trait-associated loci and looked into possible improvements in the prediction of high-level phenotypes. Finally, we studied the potential functional role of the differences observed through sex-biased gene expression and gene-level analyses. Our results suggest the need to consider sex-aware analyses for future studies to shed light onto possible sex-specific molecular mechanisms. Sex-stratified GWAS analyses for 530 traits within 452,264 individuals of European ancestry from the UK Biobank provide insights into the scope of genotype by sex (GxS) interactions and the genetics of sex differences.

DOI: 10.1038/s41588-021-00912-0

Source: https://www.nature.com/articles/s41588-021-00912-0