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...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
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Springer Nature
2024
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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 |
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