The genetic architecture of human brainstem structures and their involvement in common brain disorders
The genetic architecture of human brainstem structures and their involvement in common brain disorders
复制标题
DOI：
10.1038/s41467-020-17376-1
复制
发表时间：
2020-08-11
影响因子：
16.6
通讯作者：
Sellgren, C. M.
中科院分区：
文献类型：
--
作者：
Elvsashagen, Torbjorn;Bahrami, Shahram;Sellgren, C. M.
脑干区域支持重要的身体功能，但它们的遗传结构和参与常见的大脑疾病仍然研究不足。在这里，使用来自27，034个个体的发现样本的成像遗传学数据，我们确定了45个脑干相关的遗传基因座，包括第一个与中脑，脑桥和延髓体积相关的基因座，并将它们映射到305个基因。在7432名参与者的重复样本中，大多数位点显示出相同的效应方向，并且在标称阈值下显着。我们检测脑干体积和八个精神和神经系统疾病之间的遗传重叠。在来自5062名患有常见脑部疾病的个体和11，257名健康对照的额外临床数据中，我们观察到精神分裂症，双相情感障碍，多发性硬化症，轻度认知障碍，痴呆症和帕金森病的差异体积改变，支持脑干区域及其遗传结构在常见脑部疾病中的相关性。脑干区域的遗传结构及其与常见脑部疾病的联系尚不清楚。在这里，作者使用来自27，034名个体的MRI和GWAS数据来识别影响常见脑部疾病的遗传和形态脑干特征。
Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.