The genetic architecture of the human thalamus and its overlap with ten common brain disorders.
The genetic architecture of the human thalamus and its overlap with ten common brain disorders.
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DOI：
10.1038/s41467-021-23175-z
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发表时间：
2021-05-18
影响因子：
16.6
通讯作者：
Kaufmann T
中科院分区：
文献类型：
--
作者：
Elvsåshagen T;Shadrin A;Frei O;van der Meer D;Bahrami S;Kumar VJ;Smeland O;Westlye LT;Andreassen OA;Kaufmann T
丘脑是大脑中心的重要通信枢纽，由对意识和高级皮质功能至关重要的不同核团组成。丘脑结构和功能的改变参与了常见脑疾病的发病机制，但丘脑的遗传结构仍然在很大程度上未知。在这里，我们使用来自30，114名个体的脑部扫描和基因型数据，在42个遗传基因座和与丘脑及其核体积相关的391个基因中确定了55个主要单核苷酸多态性（SNP）。在一个独立的验证样本（n = 5173）中，发现样本的55个前导SNP中有53个显示出相同的效应方向（符号检验，P = 8.6e-14）。我们绘制了丘脑核团和180个大脑皮层区域之间的遗传关系，并发现重叠的遗传结构与丘脑皮层连接一致。丘脑体积和10个精神和神经系统疾病之间的多效性分析揭示了所有疾病的共同变体。总之，这些分析确定了与丘脑核团相关的遗传位点，并证实了丘脑在皮质功能和常见脑疾病中发挥核心作用的新观点。在几种精神疾病中已经观察到丘脑结构的差异，但尚未探索遗传重叠。在这里，作者对丘脑核体积进行了全基因组关联研究，并发现了丘脑体积和大脑疾病之间的共同遗传位点。
The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identify 55 lead single nucleotide polymorphisms (SNPs) within 42 genetic loci and 391 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5173) 53 out of the 55 lead SNPs of the discovery sample show the same effect direction (sign test, P = 8.6e-14). We map the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and find overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders reveal shared variants for all disorders. Together, these analyses identify genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders. Differences in thalamic structure have been observed in several psychiatric disorders, but the genetic overlap has not been explored. Here, the authors perform a genome-wide association study on thalamic nuclei volume and find genetic loci in common between thalamic volumes and brain disorders.
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影响因子：
11
作者：
Hibar, D. P.;Westlye, L. T.;van Erp, T. G. M.;Rasmussen, J.;Leonardo, C. D.;Faskowitz, J.;Haukvik, U. K.;Hartberg, C. B.;Doan, N. T.;Agartz, I.;Dale, A. M.;Gruber, O.;Kraemer, B.;Trost, S.;Liberg, B.;Abe, C.;Ekman, C. J.;Ingvar, M.;Landen, M.;Fears, S. C.;Freimer, N. B.;Bearden, C. E.;Sprooten, E.;Glahn, D. C.;Pearlson, G. D.;Emsell, L.;Kenney, J.;Scanlon, C.;McDonald, C.;Cannon, D. M.;Almeida, J.;Versace, A.;Caseras, X.;Lawrence, N. S.;Phillips, M. L.;Dima, D.;Delvecchio, G.;Frangou, S.;Satterthwaite, T. D.;Wolf, D.;Houenou, J.;Henry, C.;Malt, U. F.;Boen, E.;Elvsashagen, T.;Young, A. H.;Lloyd, A. J.;Goodwin, G. M.;Mackay, C. E.;Bourne, C.;Bilderbeck, A.;Abramovic, L.;Boks, M. P.;van Haren, N. E. M.;Ophoff, R. A.;Kahn, R. S.;Bauer, M.;Pfennig, A.;Alda, M.;Hajek, T.;Mwangi, B.;Soares, J. C.;Nickson, T.;Dimitrova, R.;Sussmann, J. E.;Hagenaars, S.;Whalley, H. C.;McIntosh, A. M.;Thompson, P. M.;Andreassen, O. A.
通讯作者：
Andreassen, O. A.
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
6.2
作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
通讯作者：
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium
影响因子：
16.6
作者：
Elvsashagen, Torbjorn;Bahrami, Shahram;Sellgren, C. M.
通讯作者：
Sellgren, C. M.
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M