Sex differences in genetic architecture in the UK Biobank
Sex differences in genetic architecture in the UK Biobank
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DOI：
10.1038/s41588-021-00912-0
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发表时间：
2021-09-01
期刊：
影响因子：
30.8
通讯作者：
Tenesa, Albert
中科院分区：
文献类型：
--
作者：
Bernabeu, Elena;Canela-Xandri, Oriol;Tenesa, Albert
来自英国生物库的452,264个欧洲血统个体中的530个特征的性别分层Gwas分析提供了对按性别(GXS)交互作用的基因型范围和性别差异的遗传学的洞察。男性和女性在复杂特征和患一系列疾病的风险上存在差异。性别基因(GXS)的相互作用被认为是造成这些差异的原因之一。然而，GXS的范围和基础还知之甚少。在本研究中，我们提供了对GXS的范围和机制的见解，涉及大约450,000个欧洲血统的个体和英国生物库中的530个复杂性状。我们发现，不同性状之间的遗传结构存在微小但广泛的差异。我们还发现，在某些情况下，性别不可知性分析可能遗漏了与特征相关的基因座，并研究了在预测高水平表型方面的可能改进。最后，我们通过性别偏见的基因表达和基因水平分析，研究了差异的潜在功能作用。我们的结果表明，有必要在未来的研究中考虑性别感知分析，以阐明可能的性别特异性分子机制。
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.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.