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Nat Genet. 2017 Nov;49(11):1576-1583. doi: 10.1038/ng.3973. Epub 2017 Oct 9.

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

Li Z1,2,3,4, Chen J2,5, Yu H6,7,8, He L2,4, Xu Y5, Zhang D6,7,9, Yi Q10, Li C11, Li X2, Shen J2, Song Z2, Ji W4,12, Wang M2, Zhou J2, Chen B2, Liu Y2, Wang J2, Wang P13, Yang P13, Wang Q2, Feng G5, Liu B14, Sun W14, Li B2, He G2, Li W2, Wan C2, Xu Q15, Li W2, Wen Z2, Liu K2, Huang F2, Ji J2, Ripke S16,17,18, Yue W6,7, Sullivan PF19,20, O'Donovan MC21, Shi Y1,2,3,4,10,12.

Author information

1
Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China.
2
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China.
3
Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.
4
Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, China.
5
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
6
Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
7
Institute of Mental Health, Sixth Hospital, Peking University, Beijing, China.
8
Department of Psychiatry, Jining Medical University, Jining, China.
9
Peking-Tsinghua Joint Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
10
Department of Psychiatry, First Teaching Hospital of Xinjiang Medical University, Urumqi, China.
11
Shandong Provincial Key Laboratory of Metabolic Disease and Metabolic Disease Institute of Qingdao University, Qingdao, China.
12
Changning Mental Health Center, Shanghai, China.
13
Wuhu Fourth People's Hospital, Wuhu, China.
14
Longquan Mountain Hospital of Guangxi Province, Liuzhou, China.
15
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
16
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
17
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
18
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany.
19
Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, North Carolina, USA.
20
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
21
MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.

Abstract

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 ∼50% that achieved nominal significance and ∼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.

PMID:
28991256
DOI:
10.1038/ng.3973
[Indexed for MEDLINE]

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