The Genetic Architecture of Depression in Individuals of East Asian Ancestry

萧条（经济学）全基因组关联研究人口学逻辑回归医学荟萃分析遗传学生物内科学单核苷酸多态性基因型基因宏观经济学社会学经济

作者

Olga Giannakopoulou,Kuang Lin,Xiangrui Meng,Mei‐Hsin Su,Po‐Hsiu Kuo,Roseann E. Peterson,Swapnil Awasthi,Arden Moscati,Jonathan R. I. Coleman,Nicholas Bass,Iona Y. Millwood,Yiping Chen,Zhengming Chen,Hsi‐Chung Chen,Mong‐Liang Lu,Ming‐Chyi Huang,Chun-Hsin Chen,Eli A. Stahl,Ruth J. F. Loos,Niamh Mullins,Robert J. Ursano,Ronald C. Kessler,Murray B. Stein,Srijan Sen,Laura J. Scott,Margit Burmeister,Yu Fang,Jessica Tyrrell,Yunxuan Jiang,Qingqin S. Li,Andrew M. McIntosh,Stephan Ripke,Erin C. Dunn,Kenneth S. Kendler,Robin Walters,Cathryn M. Lewis,Karoline Kuchenbaecker,Naomi R. Wray,Stephan Ripke,Manuel Mattheisen,Maciej Trzaskowski,Enda M. Byrne,Abdel Abdellaoui,Mark J. Adams,Esben Agerbo,Tracy Air,Till F. M. Andlauer,Silviu‐Alin Bacanu,Marie Bækvad‐Hansen,Aartjan T.F. Beekman,Tim B. Bigdeli,Elisabeth B. Binder,Julien Bryois,Henriette N. Buttenschøn,Jonas Bybjerg‐Grauholm,Na Cai,Enrique Castelao,Jane Christensen,Toni‐Kim Clarke,Jonathan R. I. Coleman,Lucía Colodro‐Conde,Hilary Coon,Baptiste Couvy‐Duchesne,Nick Craddock,Gregory E. Crawford,Gail Davies,Ian J. Deary,Franziska Degenhardt,Eske M. Derks,Neşe Direk,Conor V. Dolan,Erin C. Dunn,Thalia C. Eley,Valentina Escott‐Price,Farnush Farhadi Hassan Kiadeh,Hilary K. Finucane,Jerome C. Foo,Andreas J. Forstner,Josef Frank,Héléna A. Gaspar,Michael O’Donovan,Fernando S. Goes,Scott D. Gordon,Jakob Grove,Lynsey S. Hall,Christine Søholm Hansen,Thomas Hansen,Stefan Herms,Ian B. Hickie,Per Hoffmann,Georg Homuth,Carsten Horn,Jouke‐Jan Hottenga,David M. Howard,David M. Hougaard,Stefan Kloiber,Rick Jansen,Ian Jones,Lisa Jones,Eric Jorgenson,Joshua W. Knowles,Isaac S. Kohane,Julia Kraft,Warren W. Kretzschmar,Zoltán Kutalik,Yihan Li,Penelope A. Lind,Jurjen J. Luykx,Donald J. MacIntyre,Dean F. MacKinnon,Robert Maier,Wolfgang Maier,Jonathan Marchini,Hamdi Mbarek,Patrick J. McGrath,Peter McGuffin,Sarah E. Medland,Divya Mehta,Christel M. Middeldorp,Reedik Mägi,Yuri Milaneschi,Lili Milani,Francis J. McMahon,Grant W. Montgomery,Sara Mostafavi,Niamh Mullins,Matthias Nauck,Bernard Ng,Michel G. Nivard,Dale R. Nyholt,Paul F. O’Reilly,Högni Óskarsson,Michael J. Owen,Jodie N. Painter,Carsten Bøcker Pedersen,Carsten Bøcker Pedersen,Roseann E. Peterson,Erik Pettersson,David Schlessinger,Giorgio Pistis,Daniëlle Posthuma,Jorge A. Quiroz,Per Qvist,John P. Rice,Brien P. Riley,Margarita Rivera,Saira Saeed Mirza,Robert A. Schoevers,Eva C. Schulte,Ling Shen,Jianxin Shi,Stanley I. Shyn,Engilbert Sigurðsson,Grant Sinnamon,Johannes H. Smit,Daniel J. Smıth,Hreinn Stefánsson,Stacy Steinberg,Fabian Streit,Jana Strohmaier,Katherine E. Tansey,Henning Teismann,Alexander Teumer,Wesley K. Thompson,Pippa A. Thompson,Thorgeir E. Thorgeirsson,Matthew Traylor,Jens Treutlein,Vassily Trubetskoy,André G. Uitterlinden,Daniel Umbricht,Sandra Van der Auwera,Albert M. van Hemert,Alexander Viktorin,Peter M. Visscher,Yunpeng Wang,Bradley T. Webb,Shantel Weinsheimer,Jürgen Wellmann,Gonneke Willemsen,Stephanie H. Witt,Yang Wu,Hualin Simon Xi,Jian Yang,Futao Zhang,Volker Arolt,Bernhard T. Baune,Klaus Peter Berger,Dorret I. Boomsma,Sven Cichon,Udo Dannlowski,Eco J. C. de Geus,J. Raymond DePaulo,Enrico Domenici,Katharina Domschke,Tõnu Esko,Hans J. Grabe,Steven P. Hamilton,Caroline Hayward,Andrew C. Heath,Kenneth S. Kendler,Stefan Kloiber,Glyn Lewis,Qingqin S. Li,Susanne Lucae,Paul A. Madden,Patrik K. E. Magnusson,Nicholas G. Martin,Andrew M. McIntosh,Andres Metspalu,Ole Mors,Preben Bo Mortensen,Bertram Müller-Myhsok,Merete Nordentoft,Markus M. Nöthen,Michael O’Donovan,Sara A. Paciga,Nancy L. Pedersen,Brenda W.J.H. Penninx,Roy H. Perlis,Martin Preisig,James B. Potash,Martin Preisig,Marcella Rietschel,Eva C. Schulte,Thomas G. Schulze,Jordan W. Smoller,Kāri Stefánsson,Henning Tiemeier,Rudolf Uher,Henry Völzke,Myrna M. Weissman,Thomas Hansen,Cathryn M. Lewis,Douglas F. Levinson,Gerome Breen,Anders D. Børglum,Patrick F. Sullivan,Michelle Agee,Stella Aslibekyan,Adam Auton,Elizabeth Babalola,Lavínia Schüler Faccini,Jessica Bielenberg,Katarzyna Bryc,Emily Bullis,Briana Cameron,Daniella Coker,Gabriel Cuéllar-Partida,Devika Dhamija,Sayantan Das,Sarah L. Elson,Teresa Filshtein,Kipper Fletez‐Brant,Pierre Fontanillas,Will Freyman,Pooja M. Gandhi,Karl Heilbron,Barry Hicks,David A. Hinds,Karen E. Huber,Ethan M. Jewett,Yunxuan Jiang,Aaron Kleinman,Katelyn Kukar,Vanessa Lane,Keng‐Han Lin,Maya Lowe,Marie K. Luff,Jennifer C. McCreight,Matthew H. McIntyre,Kimberly F. McManus,Steven J. Micheletti,Meghan E. Moreno,Joanna L. Mountain,Sahar V. Mozaffari,Christopher P. Nelson,Jin Li,Jared O’Connell,Aaron A. Petrakovitz,G. David Poznik,Morgan Schumacher,Anjali J. Shastri,Janie F. Shelton,Jingchunzi Shi,Suyash Shringarpure,Chao Tian,Vinh Tran,Joyce Y. Tung,Xin Wang,Wei Wang,Catherine H. Weldon,Peter Wilton,Daniel Avery,Derrick Bennett,Zheng Bian,Ruth Boxall,Fiona Bragg,Ka Hung Chan,Liang Chang,Yumei Chang,Biyun Chen,Jinyan Chen,Jun Lv,Naying Chen,Ningyu Chen,Xiaofang Chen,Yi‐Ping Phoebe Chen,Zhengming Chen,Liang Cheng,Johnathan Clarke,Robert Clarke,Rory Collins,Caixia Dong,Huaidong Du,Ranran Du,Zammy Fairhurst-Hunter,Lei Fan,Shixian Feng,Zhongxi Fu,Wei Gan,Ruqin Gao,Yulian Gao,Pengfei Ge,Simon Gilbert,Weiwei Gong,Qijun Gu,Yu Guo,Zhendong Guo,Ziyan Guo,Om Kurmi,Xiao Han,Parisa Hariri,Pan He,Tianyou He,Mike Hill,Mike Holmes,Can Hou,Wei Hou,Chen Hu,Ruying Hu,Ximin Hu,Yihe Hu,Hua Hua,Yujie Hua,Yuelong Huang,Pek Kei Im,Andri Iona,Qilian Jiang,Jianrong Jin,Maria Kakkoura,Quan Kang,Christiana Kartsonaki,Rene Kerosi,Lingquan Kong,Jian Lan,Garry Lancaster,Feifei Li,Huimei Li,Jianguo Li,Liming Li,Mingqiang Li,Siu-Lung Li,Yanjie Li,Yilei Li,Zhongxiao Li,Wei‐Yu Lin,Ling Li,Chao Liu,De‐Pei Liu,Duo Liu,Fang Liu,Huilin Liu,Jiaqiu Liu,Jingchao Liu,Yongmei Liu,Yun Liu,Huajun Long,Yan Lü,Guojin Luo,Jun Lv,Silu Lv,Liangcai Ma,Enke Mao,J. A. M. McDonnell,Fanwen Meng,Jinhuai Meng,Iona Y. Millwood,Qunhua Nie,Feng Ning,Dongxia Pan,Rong Pan,Zengchang Pang,Pei Pei,Richard Gray,Alfred Pozarickij,Yijian Qian,Yulu Qin,Chan Qu,Xiaolan Ren,Paul Ryder,Sam Sansome,D. R. Schmidt,Paul Sherliker,Rajani Sohoni,Becky Stevens,Jian Su,Huarong Sun,Qiang Sun,Xiaohui Sun,Aiyu Tang,Zhenzhu Tang,Ran Tao,Xiaocao Tian,Iain Turnbull,Robin Walters,Wan Meng,Chunmei Wang,Chen Wang,Hao Wang,Junzheng Wang,Lin Wang,Ping Wang,Tao Wang,Shaojie Wang,Sisi Wang,Xiaohuan Wang,Liuping Wei,Meng‐Yu Weng,Neil Wright,Ming Wu,Xianping Wu,Shukuan Wu,Kaixu Xie,Qiaohua Xu,Qinai Xu,Xin Xu,Shichun Yan,Ling Yang,Xiaoming Yang,Jie Yang,Pang Yao,Li Yin,Bo Yu,Canqing Yu,Man Yu,Yaoming Zhai,Hao Zhang,Hui Zhang,Jun Zhang,Libo Zhang,Ningmei Zhang,Xi Zhang,Xiaoyi Zhang,Xukui Zhang,Xunfu Zhong,Ding Zhang Zhou,Gang Zhou,Jinyi Zhou,Liyuan Zhou,Weiwei Zhou,Xue Zhou,Yuan Zhou,Mingyuan Zou

出处

期刊：JAMA Psychiatry [American Medical Association]
日期：2021-09-29 卷期号：78 (11): 1258-1258 被引量：117

链接

jamanetwork.com au.dk handle.net ac.uk ac.uk handle.net suny.edu europepmc.org nih.gov ac.uk nih.govdoi.org

标识

DOI：10.1001/jamapsychiatry.2021.2099

摘要

Importance

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

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

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

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

Depression status was defined based on health records and self-report questionnaires.

Results

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 = 6.48x10⁻⁹for 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 wasr = 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

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.

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