Comparative genetic architectures of schizophrenia in East Asian and European populations

被引：413

作者：

Lam, Max ^{[1
,2
,3
,4
,5
,6
]}

Chen, Chia-Yen ^{[5
,6
,7
,8
,9
]}

Li, Zhiqiang ^{[10
,11
,12
,13
]}

Martin, Alicia R. ^{[5
,6
,7
]}

Bryois, Julien ^{[14
]}

Ma, Xixian ^{[15
]}

Gaspar, Helena ^{[16
]}

Ikeda, Masashi ^{[17
]}

Benyamin, Beben ^{[18
,19
,20
]}

Brown, Brielin C. ^{[21
,22
]}

Liu, Ruize ^{[5
,6
]}

Zhou, Wei ^{[12
,13
,23
]}

Guan, Lili ^{[24
,25
,26
,27
]}

Kamatani, Yoichiro ^{[28
,29
]}

Kim, Sung-Wan ^{[30
]}

Kubo, Michiaki ^{[31
]}

Kusumawardhani, Agung A. A. A. ^{[32
]}

Liu, Chih-Min ^{[33
,34
]}

Ma, Hong ^{[24
,25
,26
,27
]}

Periyasamy, Sathish ^{[35
,36
]}

Takahashi, Atsushi ^{[29
,37
]}

Xu, Zhida ^{[38
]}

Yu, Hao ^{[24
,25
,26
,27
]}

ZhU, Feng ^{[39
,40
,41
]}

Chen, Wei J. ^{[33
,34
,42
]}

Faraone, Stephen ^{[43
]}

Glatt, Stephen J. ^{[44
]}

He, Lin ^{[12
,13
,45
,46
]}

Hyman, Steven E. ^{[6
,47
]}

Hwu, Hai-Gwo ^{[33
,34
,42
]}

McCarro, Steven A. ^{[6
,48
]}

Neale, Benjamin M. ^{[5
,6
,7
]}

Sklar, Pamela ^{[49
]}

Wildenauer, Dieter B. ^{[50
]}

Yu, Xin ^{[24
,25
,26
,27
]}

Zhang, Dai ^{[24
,25
,26
,27
]}

Mowry, Bryan J. ^{[35
,36
]}

Lee, Jimmy ^{[51
]}

Holmans, Peter ^{[52
]}

Xu, Shuhua ^{[15
,53
,54
,55
]}

Sullivan, Patrick F. ^{[56
]}

Ripke, Stephan ^{[5
,6
,57
]}

O'Donovan, Michael C. ^{[52
]}

Daly, Mark J. ^{[5
,6
,7
,58
]}

Qin, Shengying ^{[12
,13
,59
]}

Sham, Pak ^{[60
,61
]}

Iwata, Nakao ^{[17
]}

Hong, Kyung S. ^{[62
]}

Schwab, Sibylle G. ^{[63
,64
,65
]}

Yue, Weihua ^{[24
,25
,26
,27
,66
]}

机构：

[1] Shanghai Jiao Tong Univ, Bio X Inst, Shanghai, Peoples R China

[2] Inst Mental Hlth Singapore, Res Div, Singapore, Singapore

[3] Genome Inst Singapore, Human Genet, Singapore, Singapore

[4] Northwell Hlth, Div Psychiat Res, Zucker Hillside Hosp, Glen Oaks, NY USA

[5] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[6] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[7] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[8] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[9] Biogen, Cambridge, MA USA

[10] Qingdao Univ, Biomed Sci Inst, Qingdao Branch, Shanghai Jiao Tong Univ,Bio X Inst, Qingdao, Shandong, Peoples R China

[11] Qingdao Univ, Affiliated Hosp, Qingdao, Shandong, Peoples R China

[12] Shanghai Jiao Tong Univ, Bio X Inst, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai, Peoples R China

[13] Shanghai Jiao Tong Univ, Bio X Inst, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China

[14] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[15] Univ Chinese Acad Sci, Chinese Acad Sci, CAS MPG Partner Inst Computat Biol,Shanghai Inst, Shanghai Inst Nutr & Hlth,Key Lab Computat Biol, Shanghai, Peoples R China

[16] Kings Coll London, Social Genet & Dev Psychiat, London, England

[17] Fujita Hlth Univ, Dept Psychiat, Sch Med, Toyoake, Aichi, Japan

[18] Univ South Australia, Australian Ctr Precis Hlth, Sch Hlth Sci, Canc Res Inst, Adelaide, SA, Australia

[19] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[20] South Australian Hlth & Med Res Inst, Adelaide, SA, Australia

[21] Columbia Univ, Data Sci Inst, New York, NY USA

[22] New York Genome Ctr, New York, NY USA

[23] Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Shanghai Key Lab Psychot Disorders, Sch Med, Shanghai, Peoples R China

[24] Peking Univ, Hosp 6, Beijing, Peoples R China

[25] Inst Mental Hlth, Beijing, Peoples R China

[26] Peking Univ, Natl Hlth Commiss, Key Lab Mental Hlth, Beijing, Peoples R China

[27] Peking Univ, Hosp 6, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China

[28] Univ Tokyo, Grad Sch Frontier Sci, Lab Complex Trait Genom, Tokyo, Japan

[29] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[30] Chonnam Natl Univ, Dept Psychiat, Med Sch, Gwangju, South Korea

[31] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[32] Univ Indonesia, Cipto Mangunkusumo Gen Hosp, Dept Psychiat, Jakarta, Indonesia

[33] Natl Taiwan Univ Hosp, Dept Psychiat, Taipei, Taiwan

[34] Natl Taiwan Univ, Dept Psychiat, Coll Med, Taipei, Taiwan

[35] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[36] Univ Queensland, Queensland Ctr Mental Hlth Res, Wacol, Qld, Australia

[37] Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Genom Med, Osaka, Japan

[38] Univ Med Ctr Utrecht, Dept Psychiat, Utrecht, Netherlands

[39] Xi An Jiao Tong Univ, Ctr Translat Med, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China

[40] Xi An Jiao Tong Univ, Dept Psychiat, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China

[41] Xi An Jiao Tong Univ, Ctr Brain Sci, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China

[42] Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan

[43] SUNY Syracuse, Syracuse, NY USA

[44] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Psychiat Genet Epidemiol & Neurobiol Lab PsychGEN, Syracuse, NY 13210 USA

[45] Shanghai Ctr Women & Childrens Hlth, Shanghai, Peoples R China

[46] Jinan Univ, Baoan Maternal & Child Hlth Hosp, Shenzhen, Guangdong, Peoples R China

[47] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[48] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[49] Icahn Sch Med Mt Sinai, Genet & Genom Sci, New York, NY 10029 USA

[50] Univ Western Australia, Perth, WA, Australia

来源：

NATURE GENETICS | 2019年 / 51卷 / 12期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会; 中国国家自然科学基金; 新加坡国家研究基金会;

关键词：

GENOME-WIDE ASSOCIATION; POLYGENIC RISK SCORES; INFLAMMATORY-BOWEL-DISEASE; 38 SUSCEPTIBILITY LOCI; GENOTYPE IMPUTATION; COMMON VARIANTS; HAN CHINESE; METAANALYSIS; INDIVIDUALS; SELECTION;

D O I：

10.1038/s41588-019-0512-x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1670 / +

页数：22

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