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

Authors :
Meng, Xiangrui
Navoly, Georgina
Giannakopoulou, Olga
Levey, Daniel F.
Koller, Dora
Pathak, Gita A.
Koen, Nastassja
Lin, Kuang
Adams, Mark J.
Rentería, Miguel E.
Feng, Yanzhe
Gaziano, J. Michael
Stein, Dan J.
Zar, Heather J.
Campbell, Megan L.
van Heel, David A.
Trivedi, Bhavi
Finer, Sarah
McQuillin, Andrew
Bass, Nick
Chundru, V. Kartik
Martin, Hilary C.
Huang, Qin Qin
Valkovskaya, Maria
Chu, Chia Yi
Kanjira, Susan
Kuo, Po Hsiu
Chen, Hsi Chung
Tsai, Shih Jen
Liu, Yu Li
Kendler, Kenneth S.
Peterson, Roseann E.
Cai, Na
Fang, Yu
Sen, Srijan
Scott, Laura J.
Burmeister, Margit
Loos, Ruth J.F.
Preuss, Michael H.
Actkins, Ky’Era E.V.
Davis, Lea K.
Uddin, Monica
Wani, Agaz H.
Wildman, Derek E.
Aiello, Allison E.
Ursano, Robert J.
Kessler, Ronald C.
Kanai, Masahiro
Okada, Yukinori
Sakaue, Saori
Rabinowitz, Jill A.
Maher, Brion S.
Uhl, George
Eaton, William
Cruz-Fuentes, Carlos S.
Martinez-Levy, Gabriela A.
Campos, Adrian I.
Millwood, Iona Y.
Chen, Zhengming
Li, Liming
Wassertheil-Smoller, Sylvia
Jiang, Yunxuan
Tian, Chao
Martin, Nicholas G.
Mitchell, Brittany L.
Byrne, Enda M.
Awasthi, Swapnil
Coleman, Jonathan R.I.
Ripke, Stephan
Sofer, Tamar
Walters, Robin G.
McIntosh, Andrew M.
Polimanti, Renato
Dunn, Erin C.
Stein, Murray B.
Gelernter, Joel
Lewis, Cathryn M.
Kuchenbaecker, Karoline
Meng, Xiangrui
Navoly, Georgina
Giannakopoulou, Olga
Levey, Daniel F.
Koller, Dora
Pathak, Gita A.
Koen, Nastassja
Lin, Kuang
Adams, Mark J.
Rentería, Miguel E.
Feng, Yanzhe
Gaziano, J. Michael
Stein, Dan J.
Zar, Heather J.
Campbell, Megan L.
van Heel, David A.
Trivedi, Bhavi
Finer, Sarah
McQuillin, Andrew
Bass, Nick
Chundru, V. Kartik
Martin, Hilary C.
Huang, Qin Qin
Valkovskaya, Maria
Chu, Chia Yi
Kanjira, Susan
Kuo, Po Hsiu
Chen, Hsi Chung
Tsai, Shih Jen
Liu, Yu Li
Kendler, Kenneth S.
Peterson, Roseann E.
Cai, Na
Fang, Yu
Sen, Srijan
Scott, Laura J.
Burmeister, Margit
Loos, Ruth J.F.
Preuss, Michael H.
Actkins, Ky’Era E.V.
Davis, Lea K.
Uddin, Monica
Wani, Agaz H.
Wildman, Derek E.
Aiello, Allison E.
Ursano, Robert J.
Kessler, Ronald C.
Kanai, Masahiro
Okada, Yukinori
Sakaue, Saori
Rabinowitz, Jill A.
Maher, Brion S.
Uhl, George
Eaton, William
Cruz-Fuentes, Carlos S.
Martinez-Levy, Gabriela A.
Campos, Adrian I.
Millwood, Iona Y.
Chen, Zhengming
Li, Liming
Wassertheil-Smoller, Sylvia
Jiang, Yunxuan
Tian, Chao
Martin, Nicholas G.
Mitchell, Brittany L.
Byrne, Enda M.
Awasthi, Swapnil
Coleman, Jonathan R.I.
Ripke, Stephan
Sofer, Tamar
Walters, Robin G.
McIntosh, Andrew M.
Polimanti, Renato
Dunn, Erin C.
Stein, Murray B.
Gelernter, Joel
Lewis, Cathryn M.
Kuchenbaecker, Karoline
Source :
Meng , X , Navoly , G , Giannakopoulou , O , Levey , D F , Koller , D , Pathak , G A , Koen , N , Lin , K , Adams , M J , Rentería , M E , Feng , Y , Gaziano , J M , Stein , D J , Zar , H J , Campbell , M L , van Heel , D A , Trivedi , B , Finer , S , McQuillin , A , Bass , N , Chundru , V K , Martin , H C , Huang , Q Q , Valkovskaya , M , Chu , C Y , Kanjira , S , Kuo , P H , Chen , H C , Tsai , S J , Liu , Y L , Kendler , K S , Peterson , R E , Cai , N , Fang , Y , Sen , S , Scott , L J , Burmeister , M , Loos , R J F , Preuss , M H , Actkins , KE E V , Davis , L K , Uddin , M , Wani , A H , Wildman , D E , Aiello , A E , Ursano , R J , Kessler , R C , Kanai , M , Okada , Y , Sakaue , S , Rabinowitz , J A , Maher , B S , Uhl , G , Eaton , W , Cruz-Fuentes , C S , Martinez-Levy , G A , Campos , A I , Millwood , I Y , Chen , Z , Li , L , Wassertheil-Smoller , S , Jiang , Y , Tian , C , Martin , N G , Mitchell , B L , Byrne , E M , Awasthi , S , Coleman , J R I , Ripke , S , Sofer , T , Walters , R G , McIntosh , A M , Polimanti , R , Dunn , E C , Stein , M B , Gelernter , J , Lewis , C M & Kuchenbaecker , K 2024 , ' Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference ' , Nature Genetics , vol. 56 , no. 2 , pp. 222–233 .
Publication Year :
2024

Abstract

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.<br />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.

Details

Database :
OAIster
Journal :
Meng , X , Navoly , G , Giannakopoulou , O , Levey , D F , Koller , D , Pathak , G A , Koen , N , Lin , K , Adams , M J , Rentería , M E , Feng , Y , Gaziano , J M , Stein , D J , Zar , H J , Campbell , M L , van Heel , D A , Trivedi , B , Finer , S , McQuillin , A , Bass , N , Chundru , V K , Martin , H C , Huang , Q Q , Valkovskaya , M , Chu , C Y , Kanjira , S , Kuo , P H , Chen , H C , Tsai , S J , Liu , Y L , Kendler , K S , Peterson , R E , Cai , N , Fang , Y , Sen , S , Scott , L J , Burmeister , M , Loos , R J F , Preuss , M H , Actkins , KE E V , Davis , L K , Uddin , M , Wani , A H , Wildman , D E , Aiello , A E , Ursano , R J , Kessler , R C , Kanai , M , Okada , Y , Sakaue , S , Rabinowitz , J A , Maher , B S , Uhl , G , Eaton , W , Cruz-Fuentes , C S , Martinez-Levy , G A , Campos , A I , Millwood , I Y , Chen , Z , Li , L , Wassertheil-Smoller , S , Jiang , Y , Tian , C , Martin , N G , Mitchell , B L , Byrne , E M , Awasthi , S , Coleman , J R I , Ripke , S , Sofer , T , Walters , R G , McIntosh , A M , Polimanti , R , Dunn , E C , Stein , M B , Gelernter , J , Lewis , C M & Kuchenbaecker , K 2024 , ' Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference ' , Nature Genetics , vol. 56 , no. 2 , pp. 222–233 .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1439553657
Document Type :
Electronic Resource