Brain ventricular and subcortical structures are heritable both in size and shape. Genetic influences on brain region size have been studied using conventional volumetric measures, but little is known about the genetic basis of ventricular and subcortical shapes. Here we developed pipelines to extract seven complementary shape measures for lateral ventricles, subcortical structures, and hippocampal subfields. Based on over 45,000 subjects in the UK Biobank and ABCD studies, 60 genetic loci were identified to be associated with brain shape features, 19 of which were not detectable by volumetric measures of these brain structures. Ventricular and subcortical shape features were genetically related to cognitive functions, mental health traits, and multiple brain disorders, such as the attention-deficit/hyperactivity disorder. Vertex-based shape analysis was performed to precisely localize the brain regions with these shared genetic influences. Mendelian randomization suggests brain shape causally contributes to neurological and neuropsychiatric disorders, including Alzheimer's disease and schizophrenia. Our results uncover the genetic architecture of brain shape for ventricular and subcortical structures and prioritize the genetic factors underlying disease-related shape variations.

中文翻译：

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遗传对脑室和皮层下结构形状的影响

脑室和皮层下结构在大小和形状上都是可遗传的。已经使用传统的体积测量方法研究了遗传对大脑区域大小的影响，但对心室和皮层下形状的遗传基础知之甚少。在这里，我们开发了管道来提取侧脑室、皮层下结构和海马亚场的七种互补形状测量值。根据英国生物银行和 ABCD 研究中的 45,000 多名受试者，确定了 60 个基因位点与大脑形状特征相关，其中 19 个无法通过这些大脑结构的体积测量来检测。心室和皮质下的形状特征与认知功能、心理健康特征和多种脑部疾病（如注意力缺陷/多动障碍）有遗传相关性。执行基于顶点的形状分析以精确定位具有这些共享遗传影响的大脑区域。孟德尔随机化表明大脑形状会导致神经和神经精神疾病，包括阿尔茨海默病和精神分裂症。我们的研究结果揭示了脑室和皮层下结构的大脑形状的遗传结构，并优先考虑了与疾病相关的形状变化的遗传因素。