Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia

被引:339
作者
Li, Zhiqiang [1 ,2 ,3 ,4 ,5 ]
Chen, Jianhua [3 ,6 ]
Yu, Hao [7 ,8 ,9 ]
He, Lin [3 ,5 ]
Xu, Yifeng
Zhang, Dai [7 ,8 ,10 ]
Yi, Qizhong [11 ]
Li, Changgui [12 ,13 ]
Li, Xingwang [3 ]
Shen, Jiawei [3 ]
Song, Zhijian [3 ]
Ji, Weidong [5 ,14 ]
Wang, Meng [3 ]
Zhou, Juan [3 ]
Chen, Boyu [3 ]
Liu, Yahui [3 ]
Wang, Jiqiang [3 ]
Wang, Peng [15 ]
Yang, Ping [15 ]
Wang, Qingzhong [3 ]
Feng, Guoyin [6 ]
Liu, Benxiu [16 ]
Sun, Wensheng [16 ]
Li, Baojie [3 ]
He, Guang [3 ]
Li, Weidong [3 ]
Wan, Chunling [3 ]
Xu, Qi [17 ,18 ]
Li, Wenjin [3 ]
Wen, Zujia [3 ]
Liu, Ke [3 ]
Huang, Fang [3 ]
Ji, Jue [3 ]
Ripke, Stephan [19 ,20 ,21 ]
Yue, Weihua [7 ,8 ]
Sullivan, Patrick F. [22 ,23 ,24 ]
O'Donovan, Michael C. [25 ]
Shi, Yongyong [1 ,2 ,3 ,4 ,5 ,11 ,14 ]
机构
[1] Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China
[2] Qingdao Univ, Biomed Sci Inst, SJTU Bio X Inst, Qingdao Branch, Qingdao, Peoples R China
[3] Shanghai Jiao Tong Univ, Minist Educ, Collaborat Innovat Ctr Brain Sci, Key Lab Genet Dev & Neuropsychiat Disorders,Bio X, Shanghai, Peoples R China
[4] Shanghai Jiao Tong Univ, Inst Social Cognit & Behav Sci, Shanghai, Peoples R China
[5] Shanghai Jiao Tong Univ, Inst Neuropsychiat Sci & Syst Biol Med, Shanghai, Peoples R China
[6] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China
[7] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Joint Ctr Life Sci, Beijing, Peoples R China
[8] Peking Univ, Hosp 6, Inst Mental Hlth, Beijing, Peoples R China
[9] Jining Med Univ, Dept Psychiat, Jining, Peoples R China
[10] Peking Univ, McGovern Inst Brain Res, Peking Tsinghua Joint Ctr Life Sci, PKU IDG, Beijing, Peoples R China
[11] Xinjiang Med Univ, Teaching Hosp 1, Dept Psychiat, Urumqi, Peoples R China
[12] Qingdao Univ, Shandong Prov Key Lab Metab Dis, Qingdao, Peoples R China
[13] Qingdao Univ, Metab Dis Inst, Qingdao, Peoples R China
[14] Changning Mental Hlth Ctr, Shanghai, Peoples R China
[15] Wuhu Fourth Peoples Hosp, Wuhu, Peoples R China
[16] Longquan Mt Hosp Guangxi Prov, Liuzhou, Peoples R China
[17] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing, Peoples R China
[18] Peking Union Med Coll, Beijing, Peoples R China
[19] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA
[20] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA
[21] Charite, Dept Psychiat & Psychotherapy, Berlin, Germany
[22] Univ N Carolina, Dept Genet, Chapel Hill, NC USA
[23] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA
[24] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden
[25] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Gen, Div Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales
基金
瑞典研究理事会; 国家重点研发计划; 中国博士后科学基金;
关键词
COMMON VARIANTS; CONFERRING RISK; HAN CHINESE; DISEASE; METAANALYSIS; 6P22.1; IMMUNE;
D O I
10.1038/ng.3973
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including similar to 50% that achieved nominal significance and similar to 75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses. We observed improvements in the fine-mapping resolution at many susceptibility loci. Our results provide several lines of evidence supporting candidate genes at many loci and highlight some pathways for further research. Together, our findings provide novel insight into the genetic architecture and biological etiology of schizophrenia.
引用
收藏
页码:1576 / +
页数:10
相关论文
共 69 条
[1]   Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs [J].
Adkins, D. E. ;
Aberg, K. ;
McClay, J. L. ;
Bukszar, J. ;
Zhao, Z. ;
Jia, P. ;
Stroup, T. S. ;
Perkins, D. ;
McEvoy, J. P. ;
Lieberman, J. A. ;
Sullivan, P. F. ;
van den Oord, E. J. C. G. .
MOLECULAR PSYCHIATRY, 2011, 16 (03) :321-332
[2]   NMDA receptor regulation by Src kinase signalling in excitatory synaptic transmission and plasticity [J].
Ali, DW ;
Salter, MW .
CURRENT OPINION IN NEUROBIOLOGY, 2001, 11 (03) :336-342
[3]   Hundreds of variants clustered in genomic loci and biological pathways affect human height [J].
Allen, Hana Lango ;
Estrada, Karol ;
Lettre, Guillaume ;
Berndt, Sonja I. ;
Weedon, Michael N. ;
Rivadeneira, Fernando ;
Willer, Cristen J. ;
Jackson, Anne U. ;
Vedantam, Sailaja ;
Raychaudhuri, Soumya ;
Ferreira, Teresa ;
Wood, Andrew R. ;
Weyant, Robert J. ;
Segre, Ayellet V. ;
Speliotes, Elizabeth K. ;
Wheeler, Eleanor ;
Soranzo, Nicole ;
Park, Ju-Hyun ;
Yang, Jian ;
Gudbjartsson, Daniel ;
Heard-Costa, Nancy L. ;
Randall, Joshua C. ;
Qi, Lu ;
Smith, Albert Vernon ;
Maegi, Reedik ;
Pastinen, Tomi ;
Liang, Liming ;
Heid, Iris M. ;
Luan, Jian'an ;
Thorleifsson, Gudmar ;
Winkler, Thomas W. ;
Goddard, Michael E. ;
Lo, Ken Sin ;
Palmer, Cameron ;
Workalemahu, Tsegaselassie ;
Aulchenko, Yurii S. ;
Johansson, Asa ;
Zillikens, M. Carola ;
Feitosa, Mary F. ;
Esko, Tonu ;
Johnson, Toby ;
Ketkar, Shamika ;
Kraft, Peter ;
Mangino, Massimo ;
Prokopenko, Inga ;
Absher, Devin ;
Albrecht, Eva ;
Ernst, Florian ;
Glazer, Nicole L. ;
Hayward, Caroline .
NATURE, 2010, 467 (7317) :832-838
[4]  
[Anonymous], 2012, Nature
[5]   The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].
Ardlie, Kristin G. ;
DeLuca, David S. ;
Segre, Ayellet V. ;
Sullivan, Timothy J. ;
Young, Taylor R. ;
Gelfand, Ellen T. ;
Trowbridge, Casandra A. ;
Maller, Julian B. ;
Tukiainen, Taru ;
Lek, Monkol ;
Ward, Lucas D. ;
Kheradpour, Pouya ;
Iriarte, Benjamin ;
Meng, Yan ;
Palmer, Cameron D. ;
Esko, Tonu ;
Winckler, Wendy ;
Hirschhorn, Joel N. ;
Kellis, Manolis ;
MacArthur, Daniel G. ;
Getz, Gad ;
Shabalin, Andrey A. ;
Li, Gen ;
Zhou, Yi-Hui ;
Nobel, Andrew B. ;
Rusyn, Ivan ;
Wright, Fred A. ;
Lappalainen, Tuuli ;
Ferreira, Pedro G. ;
Ongen, Halit ;
Rivas, Manuel A. ;
Battle, Alexis ;
Mostafavi, Sara ;
Monlong, Jean ;
Sammeth, Michael ;
Mele, Marta ;
Reverter, Ferran ;
Goldmann, Jakob M. ;
Koller, Daphne ;
Guigo, Roderic ;
McCarthy, Mark I. ;
Dermitzakis, Emmanouil T. ;
Gamazon, Eric R. ;
Im, Hae Kyung ;
Konkashbaev, Anuar ;
Nicolae, Dan L. ;
Cox, Nancy J. ;
Flutre, Timothee ;
Wen, Xiaoquan ;
Stephens, Matthew .
SCIENCE, 2015, 348 (6235) :648-660
[6]   Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-mediated endocytosis [J].
Bauss, Katharina ;
Knapp, Barbara ;
Jores, Pia ;
Roepman, Ronald ;
Kremer, Hannie ;
van Wijk, Erwin ;
Maerker, Tina ;
Wolfrum, Uwe .
HUMAN MOLECULAR GENETICS, 2014, 23 (15) :3923-3942
[7]   Cathepsin D and its newly identified transport receptor SEZ6L2 can modulate neurite outgrowth [J].
Boonen, Marielle ;
Staudt, Catherine ;
Gilis, Florentine ;
Oorschot, Viola ;
Klumperman, Judith ;
Jadot, Michel .
JOURNAL OF CELL SCIENCE, 2016, 129 (03) :557-568
[8]   An atlas of genetic correlations across human diseases and traits [J].
Bulik-Sullivan, Brendan ;
Finucane, Hilary K. ;
Anttila, Verneri ;
Gusev, Alexander ;
Day, Felix R. ;
Loh, Po-Ru ;
Duncan, Laramie ;
Perry, John R. B. ;
Patterson, Nick ;
Robinson, Elise B. ;
Daly, Mark J. ;
Price, Alkes L. ;
Neale, Benjamin M. .
NATURE GENETICS, 2015, 47 (11) :1236-+
[9]   LD Score regression distinguishes confounding from polygenicity in genome-wide association studies [J].
Bulik-Sullivan, Brendan K. ;
Loh, Po-Ru ;
Finucane, Hilary K. ;
Ripke, Stephan ;
Yang, Jian ;
Patterson, Nick ;
Daly, Mark J. ;
Price, Alkes L. ;
Neale, Benjamin M. .
NATURE GENETICS, 2015, 47 (03) :291-+
[10]  
Burmeister M, 2008, NAT REV GENET, V9, P527, DOI 10.1038/nrg2381