Section on Developmental Neurogenomics, Human Genetics Branch, NIMH Intramural Research Program, NIH, Bethesda, MD, USA.
Data Science and Sharing Team, NIMH, NIH, Bethesda, MD, USA.
Nat Commun. 2024 Sep 13;15(1):8041. doi: 10.1038/s41467-024-52244-2.
Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared male and female participants. Here we screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes in the UK Biobank and establish a general concordance between male and female participants in heritability estimates, genetic correlations, and variant-level effects. Notable exceptions include higher mean heritability in the female group for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and a common variant with stronger effect in male participants mapping to RBFOX1 - a gene linked to multiple neuropsychiatric disorders more common in men. This work suggests that common variant influences on human brain anatomy are largely consistent between males and females, with a few exceptions that will guide future research in growing datasets.
大型生物库极大地促进了我们对遗传因素对人类大脑解剖结构影响的理解。然而，大多数研究都是将男性和女性参与者结合起来，而不是进行比较。在这里，我们在英国生物库中筛选了 1000 多种神经解剖表型的常见遗传结构中的性别差异，并在遗传率估计、遗传相关性和变异水平效应方面建立了男性和女性参与者之间的一般一致性。值得注意的例外包括女性组的区域性体积和表面积表型的平均遗传率较高；脑岛和顶叶皮质的性别间遗传相关性明显低于 1；以及一个常见变异体在男性参与者中的效应更强，该变异体映射到 RBFOX1——一个与男性中更为常见的多种神经精神障碍相关的基因。这项工作表明，常见变异对人类大脑解剖结构的影响在男性和女性之间基本一致，但也有一些例外，这将指导未来在不断增长的数据集的研究。
