Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

被引：0

作者：

Meng, Xiangrui ^{[1
]}

Navoly, Georgina ^{[2
]}

Giannakopoulou, Olga ^{[1
]}

Levey, Daniel F. ^{[3
,4
]}

Koller, Dora ^{[3
,4
,5
]}

Pathak, Gita A. ^{[3
,4
]}

Koen, Nastassja ^{[6
,7
]}

Lin, Kuang ^{[8
]}

Adams, Mark J. ^{[9
]}

Renteria, Miguel E. ^{[10
]}

Feng, Yanzhe ^{[1
]}

Gaziano, J. Michael ^{[11
,12
,13
]}

Stein, Dan J. ^{[6
,7
]}

Zar, Heather J. ^{[14
]}

Campbell, Megan L. ^{[7
,15
]}

van Heel, David A. ^{[16
]}

Trivedi, Bhavi ^{[16
]}

Finer, Sarah ^{[17
]}

McQuillin, Andrew ^{[1
]}

Bass, Nick ^{[1
]}

Chundru, V. Kartik ^{[18
]}

Martin, Hilary C. ^{[18
]}

Huang, Qin Qin ^{[18
]}

Valkovskaya, Maria ^{[1
]}

Chu, Chia-Yi ^{[1
]}

Kanjira, Susan ^{[9
]}

Kuo, Po-Hsiu ^{[19
,20
,21
]}

Chen, Hsi-Chung ^{[21
,22
]}

Tsai, Shih-Jen ^{[23
,24
,25
]}

Liu, Yu-Li ^{[26
]}

Kendler, Kenneth S. ^{[27
]}

Peterson, Roseann E. ^{[27
,28
]}

Cai, Na ^{[29
,30
,31
]}

Fang, Yu ^{[32
]}

Sen, Srijan ^{[32
,33
]}

Scott, Laura J. ^{[34
,35
]}

Burmeister, Margit ^{[32
,33
,36
,37
]}

Loos, Ruth J. F. ^{[38
,39
]}

Preuss, Michael H. ^{[38
]}

Actkins, Ky'Era V. ^{[40
]}

Davis, Lea K. ^{[41
,42
]}

Uddin, Monica ^{[43
]}

Wani, Agaz H. ^{[43
]}

Wildman, Derek E. ^{[44
]}

Aiello, Allison E. ^{[45
]}

Ursano, Robert J. ^{[46
]}

Kessler, Ronald C. ^{[47
]}

Kanai, Masahiro ^{[48
,49
,50
]}

Okada, Yukinori ^{[48
,51
,52
]}

Sakaue, Saori ^{[48
,50
,53
]}

机构：

[1] UCL, Div Psychiat, London, England

[2] UCL, UCL Genet Inst, London, England

[3] VA CT Healthcare Ctr, Dept Psychiat, West Haven, CT USA

[4] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA

[5] Univ Barcelona, Dept Genet Microbiol & Stat, Barcelona, Spain

[6] Univ Cape Town, SAMRC Unit Risk & Resilience Mental Disorders, Dept Psychiat, Cape Town, South Africa

[7] Univ Cape Town, Neurosci Inst, Cape Town, South Africa

[8] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England

[9] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland

[10] QIMR Berghofer Med Res Inst, Dept Genet & Computat Biol, Brisbane, Qld, Australia

[11] VA Boston Healthcare Syst, Dept Med, Boston, MA USA

[12] Brigham & Womens Hosp, Dept Med, Boston, MA USA

[13] Harvard Med Sch, Dept Med, Boston, MA USA

[14] Univ Cape Town, SAMRC Unit Child & Adolescent Hlth, Dept Paediat & Child Hlth, Cape Town, South Africa

[15] Univ Cape Town, Neurosci Inst, Cape Town, South Africa

[16] Queen Mary Univ London, Blizard Inst, London, England

[17] Queen Mary Univ London, Wolfson Inst Populat Hlth, London, England

[18] Wellcome Sanger Inst, Saffron Walden, Essex, England

[19] Natl Taiwan Univ, Dept Publ Hlth, Taipei, Taiwan

[20] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei, Taiwan

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

[22] Natl Taiwan Univ Hosp, Ctr Sleep Disorders, Taipei, Taiwan

[23] Natl Yang Ming Chiao Tung Univ, Inst Brain Sci, Taipei, Taiwan

[24] Natl Yang Ming Chiao Tung Univ, Div Psychiat, Taipei, Taiwan

[25] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan

[26] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Miaoli, Taiwan

[27] VCU, Dept Psychiat, Richmond, VA USA

[28] SUNY Downstate Hlth Sci Univ, Dept Psychiat, Brooklyn, NY USA

[29] Helmholtz Munich, Helmholtz Pioneer Campus, Neuherberg, Germany

[30] Helmholtz Munich, Computat Hlth Ctr, Neuherberg, Germany

[31] Tech Univ Munich, Dept Med, Munich, Germany

[32] Univ Michigan, Michigan Neurosci Inst, Ann Arbor, MI USA

[33] Univ Michigan, Dept Psychiat, Ann Arbor, MI USA

[34] Univ Michigan, Dept Biostat, Ann Arbor, MI USA

[35] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI USA

[36] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI USA

[37] Univ Michigan, Dept Human Genet, Ann Arbor, MI USA

[38] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA

[39] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[40] Vanderbilt Univ, Med Ctr, Div Med Genet, Dept Med, Nashville, TN USA

[41] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA

[42] Vanderbilt Univ, Med Ctr, Dept Psychiat & Behav Sci, Nashville, TN USA

[43] Univ S Florida, Coll Publ Hlth, Tampa, FL USA

[44] Univ S Florida, Gen Program, Coll Publ Hlth, Tampa, FL USA

[45] Columbia Univ, Mailman Sch Publ Hlth, Robert N Butler Columbia Aging Ctr, Dept Epidemiol, New York, NY USA

[46] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD USA

[47] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA 02115 USA

[48] Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan

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

[50] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA

来源：

NATURE GENETICS | 2024年 / 56卷 / 02期

基金：

中国国家自然科学基金; 美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会; 英国生物技术与生命科学研究理事会; 英国科研创新办公室; 英国医学研究理事会; 欧洲研究理事会; 英国惠康基金;

关键词：

ENVIRONMENT INTERACTION; METAANALYSIS; ARCHITECTURE; EXPRESSION; REGRESSION; SYMPTOMS; GWAS;

D O I：

暂无

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

引用

页码：222 / +

页数：23

共 50 条

[1] Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
Xiangrui Meng
Georgina Navoly
Olga Giannakopoulou
Daniel F. Levey
Dora Koller
Gita A. Pathak
Nastassja Koen
Kuang Lin
Mark J. Adams
Miguel E. Rentería
Yanzhe Feng
J. Michael Gaziano
Dan J. Stein
Heather J. Zar
Megan L. Campbell
David A. van Heel
Bhavi Trivedi
Sarah Finer
Andrew McQuillin
Nick Bass
V. Kartik Chundru
Hilary C. Martin
Qin Qin Huang
Maria Valkovskaya
Chia-Yi Chu
Susan Kanjira
Po-Hsiu Kuo
Hsi-Chung Chen
Shih-Jen Tsai
Yu-Li Liu
Kenneth S. Kendler
Roseann E. Peterson
Na Cai
Yu Fang
Srijan Sen
Laura J. Scott
Margit Burmeister
Ruth J. F. Loos
Michael H. Preuss
Ky’Era V. Actkins
Lea K. Davis
Monica Uddin
Agaz H. Wani
Derek E. Wildman
Allison E. Aiello
Robert J. Ursano
Ronald C. Kessler
Masahiro Kanai
Yukinori Okada
Saori Sakaue
Nature Genetics, 2024, 56 : 222 - 233
[2] MESuSiE enables scalable and powerful multi-ancestry fine-mapping of causal variants in genome-wide association studies
Boran Gao
Xiang Zhou
Nature Genetics, 2024, 56 : 170 - 179
[3] MESuSiE enables scalable and powerful multi-ancestry fine-mapping of causal variants in genome-wide association studies
Gao, Boran
Zhou, Xiang
NATURE GENETICS, 2024, 56 (01) : 170 - 179
[4] Multi-ancestry genome-wide association study of asthma exacerbations
Herrera-Luis, Esther
Ortega, Victor E.
Ampleford, Elizabeth J.
Sio, Yang Yie
Granell, Raquel
de Roos, Emmely
Terzikhan, Natalie
Vergara, Ernesto Elorduy
Hernandez-Pacheco, Natalia
Perez-Garcia, Javier
Martin-Gonzalez, Elena
Lorenzo-Diaz, Fabian
Hashimoto, Simone
Brinkman, Paul
Jorgensen, Andrea L.
Yan, Qi
Forno, Erick
Vijverberg, Susanne J.
Lethem, Ryan
Espuela-Ortiz, Antonio
Gorenjak, Mario
Eng, Celeste
Gonzalez-Perez, Ruperto
Hernandez-Perez, Jose M.
Poza-Guedes, Paloma
Sardon, Olaia
Corcuera, Paula
Hawkins, Greg A.
Marsico, Annalisa
Bahmer, Thomas
Rabe, Klaus F.
Hansen, Gesine
Kopp, Matthias Volkmar
Rios, Raimon
Cruz, Maria Jesus
Gonzalez-Barcala, Francisco-Javier
Maria Olaguibel, Jose
Plaza, Vicente
Quirce, Santiago
Canino, Glorisa
Cloutier, Michelle
Del Pozo, Victoria
Rodriguez-Santana, Jose R.
Korta-Murua, Javier
Villar, Jesus
Potocnik, Uros
Figueiredo, Camila
Kabesch, Michael
Mukhopadhyay, Somnath
Pirmohamed, Munir
PEDIATRIC ALLERGY AND IMMUNOLOGY, 2022, 33 (06)
[5] LARGE-SCALE MULTI-ANCESTRY GENOME-WIDE ASSOCIATION META-ANALYSIS OF MAJOR DEPRESSION
Meng, Xiangrui
Giannakopoulou, Olga
Navoly, Georgina
Koller, Dora
Levey, Daniel
Koen, Nastassja
Loos, Ruth J. F.
Davis, Lea
Martin, Nick
Walters, Robin
Polimanti, Renato
Stein, Murray
Gelernter, Joel
Kuchenbaecker, Karoline
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2022, 63 : E49 - E49
[6] MULTI-ANCESTRY GENOME-WIDE ASSOCIATION STUDY OF ALZHEIMER'S DISEASE
Uffelmann, Emil
Wightman, Douglas
Shadrin, Alexey
Fominykh, Vera
Bahrami, Shahram
Andreassen, Ole
Posthuma, Danielle
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2024, 87 : 182 - 183
[7] A multi-ancestry genome-wide association study in type 1 diabetes
Michalek, Dominika A.
Tern, Courtney
Zhou, Wei
Robertson, Catherine C.
Farber, Emily
Campolieto, Paul
Chen, Wei-Min
Onengut-Gumuscu, Suna
Rich, Stephen S.
HUMAN MOLECULAR GENETICS, 2024, 33 (11) : 958 - 968
[8] Editorial comments on: "Multi-ancestry genome-wide association study of asthma exacerbations"
Birben, Esra
Kalayci, Omer
Eigenmann, Philippe A.
PEDIATRIC ALLERGY AND IMMUNOLOGY, 2022, 33 (07)
[9] Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study
Friligkou, Eleni
Lokhammer, Solveig
Cabrera-Mendoza, Brenda
Shen, Jie
He, Jun
Deiana, Giovanni
Zanoaga, Mihaela Diana
Asgel, Zeynep
Pilcher, Abigail
Di Lascio, Luciana
Makharashvili, Ana
Koller, Dora
Tylee, Daniel S.
Pathak, Gita A.
Polimanti, Renato
NATURE GENETICS, 2024, 56 (10) : 2036 - 2045
[10] Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus
Vergara, Candelaria
Thio, Chloe L.
Johnson, Eric
Kral, Alex H.
O'Brien, Thomas R.
Goedert, James J.
Mangia, Alessandra
Piazzolla, Valeria
Mehta, Shruti H.
Kirk, Gregory D.
Kim, Arthur Y.
Lauer, Georg M.
Chung, Raymond T.
Cox, Andrea L.
Peters, Marion G.
Khakoo, Salim I.
Alric, Laurent
Cramp, Matthew E.
Donfield, Sharyne M.
Edlin, Brian R.
Busch, Michael P.
Alexander, Graeme
Rosen, Hugo R.
Murphy, Edward L.
Latanich, Rachel
Wojcik, Genevieve L.
Taub, Margaret A.
Valencia, Ana
Thomas, David L.
Duggal, Priya
GASTROENTEROLOGY, 2019, 156 (05) : 1496 - +

← 1 2 3 4 5 →