Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank
Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank
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DOI：
10.1038/srep42140
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发表时间：
2017-02-10
影响因子：
4.6
通讯作者：
McIntosh, A. M.
中科院分区：
文献类型：
--
作者：
Reus, L. M.;Shen, X.;McIntosh, A. M.
重性抑郁症（MDD）、精神分裂症（SCZ）和双相情感障碍（BP）是常见的致残性和遗传性精神疾病，具有复杂的重叠多基因结构。患有这些疾病的个体，以及他们未受影响的亲属，在皮质纹状体和边缘系统网络中表现出广泛的结构差异。这些大脑区域的结构变异也是可遗传的和多基因的，但它们的遗传结构是否与主要精神疾病的遗传结构重叠尚不清楚。我们试图通过研究MDD、SCZ和BP的多基因风险对皮质下脑体积和白色物质（WM）显微结构的影响来解决这个问题，这是一个大样本的神经影像学数据;英国生物银行影像学研究。英国生物银行成像数据的第一个版本包括参与者重叠的遗传数据和皮质下体积（N = 978）和WM措施（N = 816）。多基因风险评分的计算是基于精神病基因组学联盟产生的全基因组关联研究结果。我们的研究结果表明，无论是皮质下体积或WM微结构，和MDD，SCZ或BP的多基因风险之间没有统计学显着的关联。这些发现表明，皮质下脑容量和WM微结构可能没有密切联系的主要精神疾病的遗传机制。
Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.