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Sparse whole-genome sequencing identifies two loci for major depressive disorder

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WOS被引频次:287
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成果类型:
期刊论文
作者:
Cai, Na*;Bigdeli, Tim B.;Kretzschmar, Warren;Li, Yihan;Liang, Jieqin;Song, Li;Hu, Jingchu;Li, Qibin;Jin, Wei;Hu, Zhenfei;Wang, Guangbiao;Wang, Linmao;Qian, Puyi;Liu, Yuan;Jiang, Tao;Lu, Yao;Zhang, Xiuqing;Yin, Ye;Li, Yingrui;Xu, Xun;Gao, Jingfang;Reimers, Mark;Webb, Todd;Riley, Brien;Bacanu, Silviu;Peterson, Roseann E.;Chen, Yiping;Zhong, Hui;Liu, Zhengrong;Wang, Gang;Sun, Jing;Sang, Hong;Jiang, Guoqing;Zhou, Xiaoyan;Li, Yi;Zhang, Wei;Wang, Xueyi;Fang, Xiang;Pan, Runde;Miao, Guodong;Zhang, Qiwen;Hu, Jian;Yu, Fengyu;Du, Bo;Sang, Wenhua;Li, Keqing;Chen, Guibing;Cai, Min;Yang, Lijun;Yang, Donglin;Ha, Baowei;Hong, Xiaohong;Deng, Hong;Li, Gongying;Li, Kan;Song, Yan;Gao, Shugui;Zhang, Jinbei;Gan, Zhaoyu;Meng, Huaqing;Pan, Jiyang;Gao, Chengge;Zhang, Kerang;Sun, Ning;Li, Youhui;Niu, Qihui;Zhang, Yutang;Liu, Tieqiao;Hu, Chunmei;Zhang, Zhen;Lv, Luxian;Dong, Jicheng;Wang, Xiaoping;Tao, Ming;Wang, Xumei;Xia, Jing;Rong, Han;He, Qiang;Liu, Tiebang;Huang, Guoping;Mei, Qiyi;Shen, Zhenming;Liu, Ying;Shen, Jianhua;Tian, Tian;Liu, Xiaojuan;Wu, Wenyuan;Gu, Danhua;Fu, Guangyi;Shi, Jianguo;Chen, Yunchun;Gan, Xiangchao;Liu, Lanfen;Wang, Lina;Yang, Fuzhong;Cong, Enzhao;Marchini, Jonathan;Yang, Huanming;Wang, Jian;Shi, Shenxun;Mott, Richard;Xu, Qi;Wang, Jun;Kendler, Kenneth S.;Flint, Jonathan
通讯作者:
Cai, Na
作者机构:
[Fu, Guangyi; Kretzschmar, Warren; Flint, Jonathan; Mott, Richard; Li, Yihan; Cai, Na; Marchini, Jonathan] Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
[Peterson, Roseann E.; Bigdeli, Tim B.; Kendler, Kenneth S.; Webb, Todd; Reimers, Mark; Bacanu, Silviu; Riley, Brien] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA.
[Jin, Wei; Hu, Jingchu; Li, Qibin; Yang, Huanming; Zhang, Xiuqing; Lu, Yao; Wang, Guangbiao; Xu, Xun; Wang, Jian; Li, Yingrui; Liang, Jieqin; Qian, Puyi; Yin, Ye; Song, Li; Jiang, Tao; Wang, Linmao; Liu, Yuan; Hu, Zhenfei; Wang, Jun] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China.
[Gao, Jingfang] Zhejiang Tradit Chinese Med Hosp, Hangzhou 310000, Zhejiang, Peoples R China.
[Chen, Yiping] Univ Oxford, CTSU, Oxford OX3 7LF, England.
通讯机构:
[Cai, Na] Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
语种:
英文
期刊:
Nature
ISSN:
0028-0836
年:
2015
卷:
523
期:
7562
页码:
588-591
文献类别:
WOS:Article
所属学科:
ESI学科类别:分子生物学&遗传学;WOS学科类别:Multidisciplinary Sciences
入藏号:
基金类别:
Wellcome Trust [WT090532/Z/09/Z, WT083573/Z/07/Z, WT089269/Z/09/Z, WT097307]; NIH [MH-100549]; Brain and Behavior Research Foundation; Agency of Science, Technology and Research (A*STAR) Graduate Academy; ERC [617306]; 973 Program [2013CB531301]; NSFC [31430048, 31222031]
机构署名:
本校为其他机构
院系归属:
湘雅二医院(第二临床学院)
摘要:
Major depressive disorder (MDD), one of the most frequently encountered forms ofmental illness and a leading cause of disability worldwide(1), poses a major challenge to genetic analysis. To date, no robustly replicated genetic loci have been identified(2), despite analysis of more than 9,000 cases(3). Here, using low-coverage whole-genome sequencing of 5,303 Chinese women with recurrent MDD selected to reduce phenotypic heterogeneity, and 5,337 controls screened to exclude MDD, we identified, and subsequently replicated in an independent sample, two loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene (P = 2.53 x 10(-10)), the other in an intron of the LHPP gene (P = 6.45 x10(-12)). Analysis of 4,509 cases with a severe subtype of MDD, melancholia, yielded an increased genetic signal at the SIRT1 locus. We attribute our success to the recruitment of relatively homogeneous cases with severe illness.
参考文献:
Kessler, R. C. & Bromet, E. J. The epidemiology of depression across cultures. Annu. Rev. Public Health 34, 119–138 (2013)
Flint, J. & Kendler, K. S. The genetics of major depression. Neuron 81, 484–503 (2014)
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium et al. A mega-analysis of genome-wide association studies for major depressive disorder. Mol. Psychiatry 18, 497–511 (2013)
Foley, D. L. et al. Genetic and environmental risk factors for depression assessed by subject-rated symptom check list versus structured clinical interview. Psychol. Med. 31, 1413–1423 (2001)
Kendler, K. S. et al. Clinical indices of familial depression in the Swedish Twin Registry. Acta Psychiatr. Scand. 115, 214–220 (2007)

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