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

被引：321

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

来源：

NATURE GENETICS | 2017年 / 49卷 / 11期

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

页码：1576 / +

页数：10

共 50 条

[21] Genome-wide meta-analysis identifies new susceptibility loci for migraine
Anttila, Verneri
Winsvold, Bendik S.
Gormley, Padhraig
Kurth, Tobias
Bettella, Francesco
McMahon, George
Kallela, Mikko
Malik, Rainer
de Vries, Boukje
Terwindt, Gisela
Medland, Sarah E.
Todt, Unda
McArdle, Wendy L.
Quaye, Lydia
Koiranen, Markku
Ikram, M. Arfan
Lehtimaki, Terho
Stam, Anine H.
Ligthart, Lannie
Wedenoja, Juho
Dunham, Ian
Neale, Benjamin M.
Palta, Priit
Hamalainen, Eija
Schuerks, Markus
Rose, Lynda M.
Buring, Julie E.
Ridker, Paul M.
Steinberg, Stacy
Stefansson, Hreinn
Jakobsson, Finnbogi
Lawlor, Debbie A.
Evans, David M.
Ring, Susan M.
Farkkila, Markus
Artto, Ville
Kaunisto, Mari A.
Freilinger, Tobias
Schoenen, Jean
Frants, Rune R.
Pelzer, Nadine
Weller, Claudia M.
Zielman, Ronald
Heath, Andrew C.
Madden, Pamela A. F.
Montgomery, Grant W.
Martin, Nicholas G.
Borck, Guntram
Goebel, Hartmut
Heinze, Axel
NATURE GENETICS, 2013, 45 (08) : 912 - U255
[22] Genome-wide Association Study Identifies New Susceptibility Loci for Posttraumatic Stress Disorder
Xie, Pingxing
Kranzler, Henry R.
Yang, Can
Zhao, Hongyu
Farrer, Lindsay A.
Gelernter, Joel
BIOLOGICAL PSYCHIATRY, 2013, 74 (09) : 656 - 663
[23] Genome-wide association study identifies five new breast cancer susceptibility loci
Clare Turnbull
Shahana Ahmed
Jonathan Morrison
David Pernet
Anthony Renwick
Mel Maranian
Sheila Seal
Maya Ghoussaini
Sarah Hines
Catherine S Healey
Deborah Hughes
Margaret Warren-Perry
William Tapper
Diana Eccles
D Gareth Evans
Maartje Hooning
Mieke Schutte
Ans van den Ouweland
Richard Houlston
Gillian Ross
Cordelia Langford
Paul D P Pharoah
Michael R Stratton
Alison M Dunning
Nazneen Rahman
Douglas F Easton
Nature Genetics, 2010, 42 : 504 - 507
[24] Genome-wide meta-analysis identifies new susceptibility loci for migraine
Verneri Anttila
Bendik S Winsvold
Padhraig Gormley
Tobias Kurth
Francesco Bettella
George McMahon
Mikko Kallela
Rainer Malik
Boukje de Vries
Gisela Terwindt
Sarah E Medland
Unda Todt
Wendy L McArdle
Lydia Quaye
Markku Koiranen
M Arfan Ikram
Terho Lehtimäki
Anine H Stam
Lannie Ligthart
Juho Wedenoja
Ian Dunham
Benjamin M Neale
Priit Palta
Eija Hamalainen
Markus Schürks
Lynda M Rose
Julie E Buring
Paul M Ridker
Stacy Steinberg
Hreinn Stefansson
Finnbogi Jakobsson
Debbie A Lawlor
David M Evans
Susan M Ring
Markus Färkkilä
Ville Artto
Mari A Kaunisto
Tobias Freilinger
Jean Schoenen
Rune R Frants
Nadine Pelzer
Claudia M Weller
Ronald Zielman
Andrew C Heath
Pamela A F Madden
Grant W Montgomery
Nicholas G Martin
Guntram Borck
Hartmut Göbel
Axel Heinze
Nature Genetics, 2013, 45 : 912 - 917
[25] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus
Kunz, Manfred
Koenig, Inke R.
Schillert, Arne
Kruppa, Jochen
Ziegler, Andreas
Grallert, Harald
Mueller-Nurasyid, Martina
Lieb, Wolfgang
Franke, Andre
Ranki, Annamari
Panelius, Jaana
Koskenmies, Sari
Hasan, Taina
Kere, Juha
Roenn, Ann-Charlotte
Simon, Jan C.
Schmidt, Enno
Wenzel, Joerg
Tueting, Thomas
Landsberg, Jennifer
Zeller, Tanja
Blankenberg, Stefan
Glaeser, Regine
Patsinakidis, Nikolaos
Kuhn, Annegret
Ibrahim, Saleh M.
EXPERIMENTAL DERMATOLOGY, 2015, 24 (07) : 510 - 515
[26] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci
Jin-Xin Bei
Yi Li
Wei-Hua Jia
Bing-Jian Feng
Gangqiao Zhou
Li-Zhen Chen
Qi-Sheng Feng
Hui-Qi Low
Hongxing Zhang
Fuchu He
E Shyong Tai
Tiebang Kang
Edison T Liu
Jianjun Liu
Yi-Xin Zeng
Nature Genetics, 2010, 42 : 599 - 603
[27] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus
Kunz, M.
Koenig, I. R.
Ziegler, A.
Ranki, A.
Koskenmies, S.
Ronn, A.
Simon, J. C.
Wenzel, J.
Landsberg, J.
Zeller, T.
Glaeser, R.
Kuhn, A.
Ibrahim, S.
EXPERIMENTAL DERMATOLOGY, 2016, 25 (03) : E18 - E18
[28] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci
Bei, Jin-Xin
Li, Yi
Jia, Wei-Hua
Feng, Bing-Jian
Zhou, Gangqiao
Chen, Li-Zhen
Feng, Qi-Sheng
Low, Hui-Qi
Zhang, Hongxing
He, Fuchu
Tai, E. Shyong
Kang, Tiebang
Liu, Edison T.
Liu, Jianjun
Zeng, Yi-Xin
NATURE GENETICS, 2010, 42 (07) : 599 - U173
[29] Genome-wide association study identifies five new breast cancer susceptibility loci
Turnbull, Clare
Ahmed, Shahana
Morrison, Jonathan
Pernet, David
Renwick, Anthony
Maranian, Mel
Seal, Sheila
Ghoussaini, Maya
Hines, Sarah
Healey, Catherine S.
Hughes, Deborah
Warren-Perry, Margaret
Tapper, William
Eccles, Diana
Evans, D. Gareth
Hooning, Maartje
Schutte, Mieke
van den Ouweland, Ans
Houlston, Richard
Ross, Gillian
Langford, Cordelia
Pharoah, Paul D. P.
Stratton, Michael R.
Dunning, Alison M.
Rahman, Nazneen
Easton, Douglas F.
NATURE GENETICS, 2010, 42 (06) : 504 - U47
[30] Genome-wide association study of colorectal cancer identifies six new susceptibility loci
Fredrick R. Schumacher
Stephanie L. Schmit
Shuo Jiao
Christopher K. Edlund
Hansong Wang
Ben Zhang
Li Hsu
Shu-Chen Huang
Christopher P. Fischer
John F. Harju
Gregory E. Idos
Flavio Lejbkowicz
Frank J. Manion
Kevin McDonnell
Caroline E. McNeil
Marilena Melas
Hedy S. Rennert
Wei Shi
Duncan C. Thomas
David J. Van Den Berg
Carolyn M. Hutter
Aaron K. Aragaki
Katja Butterbach
Bette J. Caan
Christopher S. Carlson
Stephen J. Chanock
Keith R. Curtis
Charles S. Fuchs
Manish Gala
Edward L. Giovannucci
Stephanie M. Gogarten
Richard B. Hayes
Brian Henderson
David J. Hunter
Rebecca D. Jackson
Laurence N. Kolonel
Charles Kooperberg
Sébastien Küry
Andrea LaCroix
Cathy C. Laurie
Cecelia A. Laurie
Mathieu Lemire
David Levine
Jing Ma
Karen W. Makar
Conghui Qu
Darin Taverna
Cornelia M. Ulrich
Kana Wu
Suminori Kono
Nature Communications, 6

← 1 2 3 4 5 →