Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia
A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data identifies 30 new loci for schizophrenia. These analyses improve the fine-mapping of susceptibility loci and implicate multiple pathways in schizoph...
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| Vydáno v: | Nature genetics Ročník 49; číslo 11; s. 1576 - 1583 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
New York
Nature Publishing Group US
01.11.2017
Nature Publishing Group |
| Témata: | |
| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
| On-line přístup: | Získat plný text |
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| Abstract | A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data identifies 30 new loci for schizophrenia. These analyses improve the fine-mapping of susceptibility loci and implicate multiple pathways in schizophrenia biology.
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. |
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| AbstractList | 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.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. 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. A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data identifies 30 new loci for schizophrenia. These analyses improve the fine-mapping of susceptibility loci and implicate multiple pathways in schizophrenia biology. 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. 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. 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]50% that achieved nominal significance and [similar]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. |
| Audience | Academic |
| Author | Li, Changgui Feng, Guoyin Wang, Meng Wang, Qingzhong Shi, Yongyong Shen, Jiawei Ji, Jue He, Lin Ripke, Stephan Li, Zhiqiang Wen, Zujia O'Donovan, Michael C Song, Zhijian Liu, Yahui Wang, Peng Li, Baojie Xu, Qi Yi, Qizhong Chen, Jianhua Chen, Boyu Yu, Hao Wan, Chunling Liu, Benxiu Sullivan, Patrick F Liu, Ke Xu, Yifeng Yang, Ping Zhang, Dai Li, Wenjin Zhou, Juan Li, Weidong Yue, Weihua Wang, Jiqiang Huang, Fang He, Guang Sun, Wensheng Li, Xingwang Ji, Weidong |
| Author_xml | – sequence: 1 givenname: Zhiqiang orcidid: 0000-0002-0174-9254 surname: Li fullname: Li, Zhiqiang organization: Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, 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, Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University – sequence: 2 givenname: Jianhua surname: Chen fullname: Chen, Jianhua organization: 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 Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine – sequence: 3 givenname: Hao surname: Yu fullname: Yu, Hao organization: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Institute of Mental Health, Sixth Hospital, Peking University, Department of Psychiatry, Jining Medical University – sequence: 4 givenname: Lin surname: He fullname: He, Lin organization: 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, Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University – sequence: 5 givenname: Yifeng surname: Xu fullname: Xu, Yifeng organization: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine – sequence: 6 givenname: Dai surname: Zhang fullname: Zhang, Dai organization: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Institute of Mental Health, Sixth Hospital, Peking University, Peking-Tsinghua Joint Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University – sequence: 7 givenname: Qizhong surname: Yi fullname: Yi, Qizhong organization: Department of Psychiatry, First Teaching Hospital of Xinjiang Medical University – sequence: 8 givenname: Changgui surname: Li fullname: Li, Changgui organization: Shandong Provincial Key Laboratory of Metabolic Disease and Metabolic Disease Institute of Qingdao University – sequence: 9 givenname: Xingwang surname: Li fullname: Li, Xingwang organization: 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 – sequence: 10 givenname: Jiawei surname: Shen fullname: Shen, Jiawei organization: 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 – sequence: 11 givenname: Zhijian surname: Song fullname: Song, Zhijian organization: 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 – sequence: 12 givenname: Weidong surname: Ji fullname: Ji, Weidong organization: Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Changning Mental Health Center – sequence: 13 givenname: Meng surname: Wang fullname: Wang, Meng organization: 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 – sequence: 14 givenname: Juan surname: Zhou fullname: Zhou, Juan organization: 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 – sequence: 15 givenname: Boyu surname: Chen fullname: Chen, Boyu organization: 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 – sequence: 16 givenname: Yahui surname: Liu fullname: Liu, Yahui organization: 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 – sequence: 17 givenname: Jiqiang surname: Wang fullname: Wang, Jiqiang organization: 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 – sequence: 18 givenname: Peng surname: Wang fullname: Wang, Peng organization: Wuhu Fourth People's Hospital – sequence: 19 givenname: Ping surname: Yang fullname: Yang, Ping organization: Wuhu Fourth People's Hospital – sequence: 20 givenname: Qingzhong surname: Wang fullname: Wang, Qingzhong organization: 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 – sequence: 21 givenname: Guoyin surname: Feng fullname: Feng, Guoyin organization: Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine – sequence: 22 givenname: Benxiu surname: Liu fullname: Liu, Benxiu organization: Longquan Mountain Hospital of Guangxi Province – sequence: 23 givenname: Wensheng surname: Sun fullname: Sun, Wensheng organization: Longquan Mountain Hospital of Guangxi Province – sequence: 24 givenname: Baojie surname: Li fullname: Li, Baojie organization: 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 – sequence: 25 givenname: Guang surname: He fullname: He, Guang organization: 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 – sequence: 26 givenname: Weidong surname: Li fullname: Li, Weidong organization: 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 – sequence: 27 givenname: Chunling surname: Wan fullname: Wan, Chunling organization: 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 – sequence: 28 givenname: Qi surname: Xu fullname: Xu, Qi organization: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 29 givenname: Wenjin surname: Li fullname: Li, Wenjin organization: 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 – sequence: 30 givenname: Zujia surname: Wen fullname: Wen, Zujia organization: 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 – sequence: 31 givenname: Ke surname: Liu fullname: Liu, Ke organization: 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 – sequence: 32 givenname: Fang surname: Huang fullname: Huang, Fang organization: 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 – sequence: 33 givenname: Jue surname: Ji fullname: Ji, Jue organization: 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 – sequence: 34 givenname: Stephan surname: Ripke fullname: Ripke, Stephan organization: Analytic and Translational Genetics Unit, Massachusetts General Hospital, Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin – sequence: 35 givenname: Weihua surname: Yue fullname: Yue, Weihua organization: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Institute of Mental Health, Sixth Hospital, Peking University – sequence: 36 givenname: Patrick F orcidid: 0000-0002-6619-873X surname: Sullivan fullname: Sullivan, Patrick F organization: Departments of Genetics and Psychiatry, University of North Carolina, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet – sequence: 37 givenname: Michael C orcidid: 0000-0001-7073-2379 surname: O'Donovan fullname: O'Donovan, Michael C organization: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University – sequence: 38 givenname: Yongyong orcidid: 0000-0003-1710-1505 surname: Shi fullname: Shi, Yongyong email: shiyongyong@gmail.com organization: Affiliated Hospital of Qingdao University and Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, 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, Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Department of Psychiatry, First Teaching Hospital of Xinjiang Medical University, Changning Mental Health Center |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28991256$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:136941010$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| Snippet | A genome-wide association analysis using data from Chinese individuals combined with a transethnic meta-analysis of Psychiatry Genomics Consortium data... We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data... |
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| SubjectTerms | 45/43 631/208/205/2138 692/699/476/1799 Agriculture Alleles Animal Genetics and Genomics Asian People Association analysis Biomedicine Cancer Research Chromosome Mapping Consortia Data processing Diabetes Etiology Female Gene Function Gene mapping Gene Regulatory Networks Genetic aspects Genetic Loci Genetic Predisposition to Disease Genome, Human Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotypes Health aspects Human Genetics Humans Loci Male Mental disorders Meta-analysis Metabolism Methods Population Protein Interaction Mapping Psychiatry Risk Assessment Risk factors Schizophrenia Schizophrenia - ethnology Schizophrenia - genetics Schizophrenia - physiopathology Studies |
| Title | Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia |
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