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34586374
TITLE
The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.
ABSTRACT
Importance NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.
Objective NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression.
Design, Setting, and Participants NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021.
Exposures NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts.
Main Outcomes and Measures NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts. Depression status was defined based on health records and self-report questionnaires.
Results NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts. Depression status was defined based on health records and self-report questionnaires. There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = -0.018, SE = 0.003, P = 4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10-9 for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = -0.003, SE = 0.005, P = .53 for rs4656484 and β = -0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = -0.212, SE = 0.084), contrary to findings for individuals of European descent.
Conclusions and Relevance NlmCategory: UNASSIGNED
Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts. Depression status was defined based on health records and self-report questionnaires. There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = -0.018, SE = 0.003, P = 4.43x10-8) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10-9 for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = -0.003, SE = 0.005, P = .53 for rs4656484 and β = -0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = -0.212, SE = 0.084), contrary to findings for individuals of European descent. These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.
DATE PUBLISHED
2021 Nov 01
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2021/09/30 06:00
medline 2021/09/30 06:00
entrez 2021/09/29 12:26
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Giannakopoulou O Giannakopoulou Olga O Division of Psychiatry, University College of London, London, United Kingdom.
Lin K Lin Kuang K Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Meng X Meng Xiangrui X Division of Psychiatry, University College of London, London, United Kingdom.
Su MH Su Mei-Hsin MH Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan.
Kuo PH Kuo Po-Hsiu PH Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
Peterson RE Peterson Roseann E RE Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia.
Awasthi S Awasthi Swapnil S Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Moscati A Moscati Arden A The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Coleman JRI Coleman Jonathan R I JRI National Institute for Health Research Maudsley Biomedical Research Centre, King's College London, London, United Kingdom.
Bass N Bass Nick N Division of Psychiatry, University College of London, London, United Kingdom.
Millwood IY Millwood Iona Y IY MRC Population Health Research Unit, University of Oxford, Oxford, United Kingdom.
Chen Y Chen Yiping Y MRC Population Health Research Unit, University of Oxford, Oxford, United Kingdom.
Chen Z Chen Zhengming Z MRC Population Health Research Unit, University of Oxford, Oxford, United Kingdom.
Chen HC Chen Hsi-Chung HC Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
Lu ML Lu Mong-Liang ML School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Huang MC Huang Ming-Chyi MC Department of Psychiatry, Taipei City Psychiatric Center, Taipei, Taiwan.
Chen CH Chen Chun-Hsin CH School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Stahl EA Stahl Eli A EA The Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, New York.
Loos RJF Loos Ruth J F RJF The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Mullins N Mullins Niamh N The Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, New York.
Ursano RJ Ursano Robert J RJ Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Kessler RC Kessler Ronald C RC Harvard Medical School, Boston, Massachusetts.
Stein MB Stein Murray B MB University of California, San Diego, La Jolla, California.
Sen S Sen Srijan S Michigan Neuroscience Institute, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.
Scott LJ Scott Laura J LJ Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.
Burmeister M Burmeister Margit M Molecular & Behavioral Neuroscience Institute, Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, Michigan.
Fang Y Fang Yu Y Michigan Neuroscience Institute, University of Michigan, Ann Arbor, Michigan.
Tyrrell J Tyrrell Jess J University of Exeter Medical School, University of Exeter, The RILD Building, RD&E Hospital, Exeter, United Kingdom.
Jiang Y Jiang Yunxuan Y 23andme, Inc, Sunnyvale, California.
Tian C Tian Chao C 23andme, Inc, Sunnyvale, California.
McIntosh AM McIntosh Andrew M AM Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Ripke S Ripke Stephan S Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
Dunn EC Dunn Erin C EC Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Kendler KS Kendler Kenneth S KS Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, Virginia.
Walters RG Walters Robin G RG MRC Population Health Research Unit, University of Oxford, Oxford, United Kingdom.
Lewis CM Lewis Cathryn M CM National Institute for Health Research Maudsley Biomedical Research Centre, King's College London, London, United Kingdom.
Kuchenbaecker K Kuchenbaecker Karoline K UCL Genetics Institute, University College of London, London, United Kingdom.
23andMe Research Team, China Kadoorie Biobank Collaborative Group, and Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Wray Naomi R NR
Ripke Stephan S
Mattheisen Manuel M
Trzaskowski Maciej M
Byrne Enda M EM
Abdellaoui Abdel A
Adams Mark J MJ
Agerbo Esben E
Air Tracy M TM
Andlauer Till F M TFM
Bacanu Silviu-Alin SA
Bækvad-Hansen Marie M
Beekman Aartjan T F ATF
Bigdeli Tim B TB
Binder Elisabeth B EB
Bryois Julien J
Buttenschøn Henriette N HN
Bybjerg-Grauholm Jonas J
Cai Na N
Castelao Enrique E
Christensen Jane Hvarregaard JH
Clarke Toni-Kim TK
Coleman Jonathan R I JRI
Colodro-Conde Lucía L
Coon Hilary H
Couvy-Duchesne Baptiste B
Craddock Nick N
Crawford Gregory E GE
Davies Gail G
Deary Ian J IJ
Degenhardt Franziska F
Derks Eske M EM
Direk Nese N
Dolan Conor V CV
Dunn Erin C EC
Eley Thalia C TC
Escott-Price Valentina V
Kiadeh Farnush Farhadi Hassan FFH
Finucane Hilary K HK
Foo Jerome C JC
Forstner Andreas J AJ
Frank Josef J
Gaspar Héléna A HA
Gill Michael M
Goes Fernando S FS
Gordon Scott D SD
Grove Jakob J
Hall Lynsey S LS
Hansen Christine Søholm CS
Hansen Thomas F TF
Herms Stefan S
Hickie Ian B IB
Hoffmann Per P
Homuth Georg G
Horn Carsten C
Hottenga Jouke-Jan JJ
Howard David M DM
Hougaard David M DM
Ising Marcus M
Jansen Rick R
Jones Ian I
Jones Lisa A LA
Jorgenson Eric E
Knowles James A JA
Kohane Isaac S IS
Kraft Julia J
Kretzschmar Warren W WW
Kutalik Zoltán Z
Li Yihan Y
Lind Penelope A PA
Luykx Jurjen J JJ
MacIntyre Donald J DJ
MacKinnon Dean F DF
Maier Robert M RM
Maier Wolfgang W
Marchini Jonathan J
Mbarek Hamdi H
McGrath Patrick P
McGuffin Peter P
Medland Sarah E SE
Mehta Divya D
Middeldorp Christel M CM
Mihailov Evelin E
Milaneschi Yuri Y
Milani Lili L
Mondimore Francis M FM
Montgomery Grant W GW
Mostafavi Sara S
Mullins Niamh N
Nauck Matthias M
Ng Bernard B
Nivard Michel G MG
Nyholt Dale R DR
O'Reilly Paul F PF
Oskarsson Hogni H
Owen Michael J MJ
Painter Jodie N JN
Pedersen Carsten Bøcker CB
Pedersen Marianne Giørtz MG
Peterson Roseann E RE
Pettersson Erik E
Peyrot Wouter J WJ
Pistis Giorgio G
Posthuma Danielle D
Quiroz Jorge A JA
Qvist Per P
Rice John P JP
Riley Brien P BP
Rivera Margarita M
Mirza Saira Saeed SS
Schoevers Robert R
Schulte Eva C EC
Shen Ling L
Shi Jianxin J
Shyn Stanley I SI
Sigurdsson Engilbert E
Sinnamon Grant C B GCB
Smit Johannes H JH
Smith Daniel J DJ
Stefansson Hreinn H
Steinberg Stacy S
Streit Fabian F
Strohmaier Jana J
Tansey Katherine E KE
Teismann Henning H
Teumer Alexander A
Thompson Wesley W
Thompson Pippa A PA
Thorgeirsson Thorgeir E TE
Traylor Matthew M
Treutlein Jens J
Trubetskoy Vassily V
Uitterlinden André G AG
Umbricht Daniel D
Van der Auwera Sandra S
van Hemert Albert M AM
Viktorin Alexander A
Visscher Peter M PM
Wang Yunpeng Y
Webb Bradley T BT
Weinsheimer Shantel Marie SM
Wellmann Jürgen J
Willemsen Gonneke G
Witt Stephanie H SH
Wu Yang Y
Xi Hualin S HS
Yang Jian J
Zhang Futao F
Arolt Volker V
Baune Bernhard T BT
Berger Klaus K
Boomsma Dorret I DI
Cichon Sven S
Dannlowski Udo U
de Geus Ejc E
DePaulo J Raymond JR
Domenici Enrico E
Domschke Katharina K
Esko Tõnu T
Grabe Hans J HJ
Hamilton Steven P SP
Hayward Caroline C
Heath Andrew C AC
Kendler Kenneth S KS
Kloiber Stefan S
Lewis Glyn G
Li Qingqin S QS
Lucae Susanne S
Madden Pamela Af PA
Magnusson Patrik K PK
Martin Nicholas G NG
McIntosh Andrew M AM
Metspalu Andres A
Mors Ole O
Mortensen Preben Bo PB
Müller-Myhsok Bertram B
Nordentoft Merete M
Nöthen Markus M MM
O'Donovan Michael C MC
Paciga Sara A SA
Pedersen Nancy L NL
Penninx Brenda Wjh BW
Perlis Roy H RH
Porteous David J DJ
Potash James B JB
Preisig Martin M
Rietschel Marcella M
Schaefer Catherine C
Schulze Thomas G TG
Smoller Jordan W JW
Stefansson Kari K
Tiemeier Henning H
Uher Rudolf R
Völzke Henry H
Weissman Myrna M MM
Werge Thomas T
Lewis Cathryn M CM
Levinson Douglas F DF
Breen Gerome G
Børglum Anders D AD
Sullivan Patrick F PF
Agee Michelle M
Aslibekyan Stella S
Auton Adam A
Babalola Elizabeth E
Bell Robert K RK
Bielenberg Jessica J
Bryc Katarzyna K
Bullis Emily E
Cameron Briana B
Coker Daniella D
Cuellar Partida Gabriel G
Dhamija Devika D
Das Sayantan S
Elson Sarah L SL
Filshtein Teresa T
Fletez-Brant Kipper K
Fontanillas Pierre P
Freyman Will W
Gandhi Pooja M PM
Heilbron Karl K
Hicks Barry B
Hinds David A DA
Huber Karen E KE
Jewett Ethan M EM
Jiang Yunxuan Y
Kleinman Aaron A
Kukar Katelyn K
Lane Vanessa V
Lin Keng-Han KH
Lowe Maya M
Luff Marie K MK
McCreight Jennifer C JC
McIntyre Matthew H MH
McManus Kimberly F KF
Micheletti Steven J SJ
Moreno Meghan E ME
Mountain Joanna L JL
Mozaffari Sahar V SV
Nandakumar Priyanka P
Noblin Elizabeth S ES
O'Connell Jared J
Petrakovitz Aaron A AA
Poznik G David GD
Schumacher Morgan M
Shastri Anjali J AJ
Shelton Janie F JF
Shi Jingchunzi J
Shringarpure Suyash S
Tian Chao C
Tran Vinh V
Tung Joyce Y JY
Wang Xin X
Wang Wei W
Weldon Catherine H CH
Wilton Peter P
Avery Daniel D
Bennett Derrick D
Bian Zheng Z
Boxall Ruth R
Bragg Fiona F
Chan Ka Hung KH
Chang Liang L
Chang Yumei Y
Chen Biyun B
Chen Jinyan J
Chen Junshi J
Chen Naying N
Chen Ningyu N
Chen Xiaofang X
Chen Yiping Y
Chen Zhengming Z
Cheng Liang L
Clarke Johnathan J
Clarke Robert R
Collins Rory R
Dong Caixia C
Du Huaidong H
Du Ranran R
Fairhurst-Hunter Zammy Z
Fan Lei L
Feng Shixian S
Fu Zhongxi Z
Gan Wei W
Gao Ruqin R
Gao Yulian Y
Ge Pengfei P
Gilbert Simon S
Gong Weiwei W
Gu Qijun Q
Guo Yu Y
Guo Zhendong Z
Guo Ziyan Z
Hacker Alex A
Han Xiao X
Hariri Parisa P
He Pan P
He Tianyou T
Hill Mike M
Holmes Michael M
Hou Can C
Hou Wei W
Hu Chen C
Hu Ruying R
Hu Ximin X
Hu Yihe Y
Hua Hua H
Hua Yujie Y
Huang Yuelong Y
Im Pek Kei PK
Iona Andri A
Jiang Qilian Q
Jin Jianrong J
Kakkoura Maria M
Kang Quan Q
Kartsonaki Christiana C
Kerosi Rene R
Kong Ling L
Lan Jian J
Lancaster Garry G
Li Feifei F
Li Huimei H
Li Jianguo J
Li Liming L
Li Mingqiang M
Li Shanpeng S
Li Yanjie Y
Li Yilei Y
Li Zhongxiao Z
Lin Kuang K
Lingli Lingli L
Liu Chao C
Liu Depei D
Liu Duo D
Liu Fang F
Liu Huilin H
Liu Jiaqiu J
Liu Jingchao J
Liu Yongmei Y
Liu Yun Y
Long Huajun H
Lu Yan Y
Luo Guojin G
Lv Jun J
Lv Silu S
Ma Liangcai L
Mao Enke E
McDonnell John J
Meng Fanwen F
Meng Jinhuai J
Millwood Iona I
Nie Qunhua Q
Ning Feng F
Pan Dongxia D
Pan Rong R
Pang Zengchang Z
Pei Pei P
Peto Richard R
Pozarickij Alfred A
Qian Yijian Y
Qin Yulu Y
Qu Chan C
Ren Xiaolan X
Ryder Paul P
Sansome Sam S
Schmidt Dan D
Sherliker Paul P
Sohoni Rajani R
Stevens Becky B
Su Jian J
Sun Huarong H
Sun Qiang Q
Sun Xiaohui X
Tang Aiyu A
Tang Zhenzhu Z
Tao Ran R
Tian Xiaocao X
Turnbull Iain I
Walters Robin R
Wan Meng M
Wang Chunmei C
Wang Chen C
Wang Hao H
Wang Junzheng J
Wang Lin L
Wang Ping P
Wang Tao T
Wang Shaojie S
Wang Sisi S
Wang Xiaohuan X
Wei Liuping L
Weng Min M
Wright Neil N
Wu Ming M
Wu Xianping X
Wu Shukuan S
Xie Kaixu K
Xu Qiaohua Q
Xu Qinai Q
Xu Xin X
Yan Shichun S
Yang Ling L
Yang Xiaoming X
Yang Jie J
Yao Pang P
Yin Li L
Yu Bo B
Yu Canqing C
Yu Min M
Zhai Yaoming Y
Zhang Hao H
Zhang Hui H
Zhang Jun J
Zhang Libo L
Zhang Ningmei N
Zhang Xi X
Zhang Xiaoyi X
Zhang Xukui X
Zhong Xunfu X
Zhou Ding Zhang DZ
Zhou Gang G
Zhou Jinyi J
Zhou Liyuan L
Zhou Weiwei W
Zhou Xue X
Zhou Yonglin Y
Zou Mingyuan M
JOURNAL
VOLUME: 78
ISSUE: 11
TITLE: JAMA psychiatry
ISOABBREVIATION: JAMA Psychiatry
YEAR: 2021
MONTH: Nov
DAY: 01
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2168-6238
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: JAMA Psychiatry
COUNTRY: United States
ISSNLINKING: 2168-622X
NLMUNIQUEID: 101589550
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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