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

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 measu...

Full description

Bibliographic Details
Main Authors: Meng, X, Navoly, G, Giannakopoulou, O, Levey, DF, Koller, D, Pathak, GA, Koen, N, Lin, K, Adams, MJ, Rentería, ME, Feng, Y, Gaziano, JM, Stein, DJ, Zar, HJ, Campbell, ML, van Heel, DA, Trivedi, B, Finer, S, McQuillin, A, Bass, N, Chundru, VK, Martin, HC, Huang, QQ, Valkovskaya, M, Chu, C-Y, Kanjira, S, Kuo, P-H, Chen, H-C, Tsai, S-J, Liu, Y-L, Kendler, KS, Peterson, RE, Cai, N, Fang, Y, Sen, S, Scott, LJ, Burmeister, M, Loos, RJF, Preuss, MH, Actkins, KV, Davis, LK, Uddin, M, Wani, AH, Wildman, DE, Aiello, AE, Ursano, RJ, Kessler, RC, Kanai, M, Okada, Y, Sakaue, S, Millwood, IY, Chen, Z, Walters, RG
Other Authors: PGC-MDD Working Group
Format: Journal article
Language:English
Published: Springer Nature 2024
_version_ 1797112508666871808
author Meng, X
Navoly, G
Giannakopoulou, O
Levey, DF
Koller, D
Pathak, GA
Koen, N
Lin, K
Adams, MJ
Rentería, ME
Feng, Y
Gaziano, JM
Stein, DJ
Zar, HJ
Campbell, ML
van Heel, DA
Trivedi, B
Finer, S
McQuillin, A
Bass, N
Chundru, VK
Martin, HC
Huang, QQ
Valkovskaya, M
Chu, C-Y
Kanjira, S
Kuo, P-H
Chen, H-C
Tsai, S-J
Liu, Y-L
Kendler, KS
Peterson, RE
Cai, N
Fang, Y
Sen, S
Scott, LJ
Burmeister, M
Loos, RJF
Preuss, MH
Actkins, KV
Davis, LK
Uddin, M
Wani, AH
Wildman, DE
Aiello, AE
Ursano, RJ
Kessler, RC
Kanai, M
Okada, Y
Sakaue, S
Millwood, IY
Chen, Z
Walters, RG
author2 PGC-MDD Working Group
author_facet PGC-MDD Working Group
Meng, X
Navoly, G
Giannakopoulou, O
Levey, DF
Koller, D
Pathak, GA
Koen, N
Lin, K
Adams, MJ
Rentería, ME
Feng, Y
Gaziano, JM
Stein, DJ
Zar, HJ
Campbell, ML
van Heel, DA
Trivedi, B
Finer, S
McQuillin, A
Bass, N
Chundru, VK
Martin, HC
Huang, QQ
Valkovskaya, M
Chu, C-Y
Kanjira, S
Kuo, P-H
Chen, H-C
Tsai, S-J
Liu, Y-L
Kendler, KS
Peterson, RE
Cai, N
Fang, Y
Sen, S
Scott, LJ
Burmeister, M
Loos, RJF
Preuss, MH
Actkins, KV
Davis, LK
Uddin, M
Wani, AH
Wildman, DE
Aiello, AE
Ursano, RJ
Kessler, RC
Kanai, M
Okada, Y
Sakaue, S
Millwood, IY
Chen, Z
Walters, RG
author_sort Meng, X
collection OXFORD
description 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.
first_indexed 2024-03-07T08:26:37Z
format Journal article
id oxford-uuid:af386660-deb0-45d0-94d8-35f84c48a5ca
institution University of Oxford
language English
last_indexed 2024-03-07T08:26:37Z
publishDate 2024
publisher Springer Nature
record_format dspace
spelling oxford-uuid:af386660-deb0-45d0-94d8-35f84c48a5ca2024-02-15T11:31:25ZMulti-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inferenceJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:af386660-deb0-45d0-94d8-35f84c48a5caEnglishSymplectic ElementsSpringer Nature2024Meng, XNavoly, GGiannakopoulou, OLevey, DFKoller, DPathak, GAKoen, NLin, KAdams, MJRentería, MEFeng, YGaziano, JMStein, DJZar, HJCampbell, MLvan Heel, DATrivedi, BFiner, SMcQuillin, ABass, NChundru, VKMartin, HCHuang, QQValkovskaya, MChu, C-YKanjira, SKuo, P-HChen, H-CTsai, S-JLiu, Y-LKendler, KSPeterson, RECai, NFang, YSen, SScott, LJBurmeister, MLoos, RJFPreuss, MHActkins, KVDavis, LKUddin, MWani, AHWildman, DEAiello, AEUrsano, RJKessler, RCKanai, MOkada, YSakaue, SMillwood, IYChen, ZWalters, RGPGC-MDD Working GroupChina Kadoorie Biobank Collaborative Groupthe 23andMe Research TeamGenes and Health Research TeamBioBank Japan ProjectMost 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.
spellingShingle Meng, X
Navoly, G
Giannakopoulou, O
Levey, DF
Koller, D
Pathak, GA
Koen, N
Lin, K
Adams, MJ
Rentería, ME
Feng, Y
Gaziano, JM
Stein, DJ
Zar, HJ
Campbell, ML
van Heel, DA
Trivedi, B
Finer, S
McQuillin, A
Bass, N
Chundru, VK
Martin, HC
Huang, QQ
Valkovskaya, M
Chu, C-Y
Kanjira, S
Kuo, P-H
Chen, H-C
Tsai, S-J
Liu, Y-L
Kendler, KS
Peterson, RE
Cai, N
Fang, Y
Sen, S
Scott, LJ
Burmeister, M
Loos, RJF
Preuss, MH
Actkins, KV
Davis, LK
Uddin, M
Wani, AH
Wildman, DE
Aiello, AE
Ursano, RJ
Kessler, RC
Kanai, M
Okada, Y
Sakaue, S
Millwood, IY
Chen, Z
Walters, RG
Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
title Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
title_full Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
title_fullStr Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
title_full_unstemmed Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
title_short Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference
title_sort multi ancestry genome wide association study of major depression aids locus discovery fine mapping gene prioritization and causal inference
work_keys_str_mv AT mengx multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT navolyg multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT giannakopoulouo multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT leveydf multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT kollerd multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT pathakga multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT koenn multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT link multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT adamsmj multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT renteriame multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT fengy multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT gazianojm multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT steindj multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT zarhj multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT campbellml multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT vanheelda multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT trivedib multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT finers multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT mcquillina multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT bassn multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT chundruvk multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT martinhc multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT huangqq multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT valkovskayam multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT chucy multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT kanjiras multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT kuoph multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT chenhc multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT tsaisj multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT liuyl multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT kendlerks multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT petersonre multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT cain multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT fangy multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT sens multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT scottlj multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT burmeisterm multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT loosrjf multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT preussmh multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT actkinskv multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT davislk multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT uddinm multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT waniah multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT wildmande multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT aielloae multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT ursanorj multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT kesslerrc multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT kanaim multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT okaday multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT sakaues multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT millwoodiy multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT chenz multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference
AT waltersrg multiancestrygenomewideassociationstudyofmajordepressionaidslocusdiscoveryfinemappinggeneprioritizationandcausalinference