Comparative genetic architectures of schizophrenia in East Asian and European populations View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-11-18

AUTHORS

Max Lam, Chia-Yen Chen, Zhiqiang Li, Alicia R. Martin, Julien Bryois, Xixian Ma, Helena Gaspar, Masashi Ikeda, Beben Benyamin, Brielin C. Brown, Ruize Liu, Wei Zhou, Lili Guan, Yoichiro Kamatani, Sung-Wan Kim, Michiaki Kubo, Agung A. A. A. Kusumawardhani, Chih-Min Liu, Hong Ma, Sathish Periyasamy, Atsushi Takahashi, Zhida Xu, Hao Yu, Feng Zhu, Wei J. Chen, Stephen Faraone, Stephen J. Glatt, Lin He, Steven E. Hyman, Hai-Gwo Hwu, Steven A. McCarroll, Benjamin M. Neale, Pamela Sklar, Dieter B. Wildenauer, Xin Yu, Dai Zhang, Bryan J. Mowry, Jimmy Lee, Peter Holmans, Shuhua Xu, Patrick F. Sullivan, Stephan Ripke, Michael C. O’Donovan, Mark J. Daly, Shengying Qin, Pak Sham, Nakao Iwata, Kyung S. Hong, Sibylle G. Schwab, Weihua Yue, Ming Tsuang, Jianjun Liu, Xiancang Ma, René S. Kahn, Yongyong Shi, Hailiang Huang

ABSTRACT

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations. More... »

PAGES

1670-1678

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    12

    VOLUME

    51

    Author Affiliations

  • Research Division, Institute of Mental Health Singapore, Singapore, Singapore
  • Biogen, Cambridge, MA, USA
  • Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China
  • Department of Medicine, Harvard Medical School, Boston, MA, USA
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
  • Social Genetic and Developmental Psychiatry, King’s College London, London, UK
  • Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan
  • South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  • New York Genome Center, New York, NY, USA
  • Stanley Center for Psychiatric Research, the Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
  • RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Psychiatry, Cipto Mangunkusumo General Hospital, Universitas Indonesia, Jakarta, Indonesia
  • Department of Psychiatry, National Taiwan University College of Medicine, Taipei, Taiwan
  • Queensland Center for Mental Health Research, The University of Queensland, Wacol, Queensland, Australia
  • Department of Genomic Medicine, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan
  • Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands
  • Center for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  • Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
  • The State University of New York, Syracuse, NY, USA
  • Psychiatric Genetic Epidemiology and Neurobiology Laboratory (PsychGENe lab), Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA
  • Baoan Maternal and Child Health Hospital, Jinan University, Shenzhen, China
  • Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
  • Department of Genetics, Harvard Medical School, Boston, MA, USA
  • Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • University of Western Australia, Perth, Western Australia, Australia
  • Institute of Mental Health, Singapore, Singapore
  • MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK
  • Collaborative Innovation Center of Genetics and Development, Shanghai, China
  • Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
  • Department of Psychiatry and Psychotherapy Charité – Universitätsmedizin, Berlin, Germany
  • Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland
  • Collaborative Innovation Center, Jining Medical University, Jining, China
  • Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
  • Department of Psychiatry, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
  • Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia
  • IDG/McGovern Institute for Brain Research at Peking University, Beijing, China
  • Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, San Diego, CA, USA
  • Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • Clinical Research Center for Mental Disease of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  • Department of Psychiatry, Brain Center Rudolf Magnus, UMC Utrecht, Utrecht, the Netherlands
  • Department of Psychiatry, First Teaching Hospital of Xinjiang Medical University, Ürümqi, China
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-019-0512-x

    DOI

    http://dx.doi.org/10.1038/s41588-019-0512-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1122664870

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31740837


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