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 E.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; Jill A. Rabinowitz; Brion S. Maher; George Uhl; William Eaton; Carlos S. Cruz-Fuentes; Gabriela A. Martinez-Levy; Adrian I. Campos; Iona Y. Millwood; Zhengming Chen; Liming Li; Sylvia Wassertheil-Smoller; Yunxuan Jiang; Chao Tian; Nicholas G. Martin; Brittany L. Mitchell; Enda M. Byrne; Swapnil Awasthi; Jonathan R.I. Coleman; Stephan Ripke; Tamar Sofer; Robin G. Walters; Andrew M. McIntosh; Renato Polimanti; Erin C. Dunn; Murray B. Stein; Joel Gelernter; Cathryn M. Lewis; Karoline Kuchenbaecker

doi:10.1038/s41588-023-01596-4

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 BassV. 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 E.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, Jill A. Rabinowitz, Brion S. Maher, George Uhl, William Eaton, Carlos S. Cruz-Fuentes, Gabriela A. Martinez-Levy, Adrian I. Campos, Iona Y. Millwood, Zhengming Chen, Liming Li, Sylvia Wassertheil-Smoller, Yunxuan Jiang, Chao Tian, Nicholas G. Martin, Brittany L. Mitchell, Enda M. Byrne, Swapnil Awasthi, Jonathan R.I. Coleman, Stephan Ripke, Tamar Sofer, Robin G. Walters, Andrew M. McIntosh, Renato Polimanti, Erin C. Dunn, Murray B. Stein, Joel Gelernter, Cathryn M. Lewis, Karoline Kuchenbaecker^*

^*Corresponding author af dette arbejde

Loos Group

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

87 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	56
Udgave nummer	2
Sider (fra-til)	222–233
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-023-01596-4
Status	Udgivet - 2024

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Publisher Copyright:
© 2024, The Author(s).

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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., ... Kuchenbaecker, K. (2024). Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference. Nature Genetics, 56(2), 222–233. https://doi.org/10.1038/s41588-023-01596-4

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, CY, Kanjira, S, Kuo, PH, Chen, HC, Tsai, SJ, Liu, YL, Kendler, KS, Peterson, RE, Cai, N, Fang, Y, Sen, S, Scott, LJ, Burmeister, M, Loos, RJF, Preuss, MH, Actkins, KEEV, Davis, LK, Uddin, M, Wani, AH, Wildman, DE, Aiello, AE, Ursano, RJ, Kessler, RC, Kanai, M, Okada, Y, Sakaue, S, Rabinowitz, JA, Maher, BS, Uhl, G, Eaton, W, Cruz-Fuentes, CS, Martinez-Levy, GA, Campos, AI, Millwood, IY, Chen, Z, Li, L, Wassertheil-Smoller, S, Jiang, Y, Tian, C, Martin, NG, Mitchell, BL, Byrne, EM, Awasthi, S, Coleman, JRI, Ripke, S, Sofer, T, Walters, RG, McIntosh, AM, Polimanti, R, Dunn, EC, Stein, MB, Gelernter, J, Lewis, CM & Kuchenbaecker, K 2024, 'Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference', Nature Genetics, bind 56, nr. 2, s. 222–233. https://doi.org/10.1038/s41588-023-01596-4

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

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.",

author = "Xiangrui Meng and Georgina Navoly and Olga Giannakopoulou and Levey, {Daniel F.} and Dora Koller and Pathak, {Gita A.} and Nastassja Koen and Kuang Lin and Adams, {Mark J.} and Renter{\'i}a, {Miguel E.} and Yanzhe Feng and Gaziano, {J. Michael} and Stein, {Dan J.} and Zar, {Heather J.} and Campbell, {Megan L.} and {van Heel}, {David A.} and Bhavi Trivedi and Sarah Finer and Andrew McQuillin and Nick Bass and Chundru, {V. Kartik} and Martin, {Hilary C.} and Huang, {Qin Qin} and Maria Valkovskaya and Chu, {Chia Yi} and Susan Kanjira and Kuo, {Po Hsiu} and Chen, {Hsi Chung} and Tsai, {Shih Jen} and Liu, {Yu Li} and Kendler, {Kenneth S.} and Peterson, {Roseann E.} and Na Cai and Yu Fang and Srijan Sen and Scott, {Laura J.} and Margit Burmeister and Loos, {Ruth J.F.} and Preuss, {Michael H.} and Actkins, {Ky{\textquoteright}Era E.V.} and Davis, {Lea K.} and Monica Uddin and Wani, {Agaz H.} and Wildman, {Derek E.} and Aiello, {Allison E.} and Ursano, {Robert J.} and Kessler, {Ronald C.} and Masahiro Kanai and Yukinori Okada and Saori Sakaue and Rabinowitz, {Jill A.} and Maher, {Brion S.} and George Uhl and William Eaton and Cruz-Fuentes, {Carlos S.} and Martinez-Levy, {Gabriela A.} and Campos, {Adrian I.} and Millwood, {Iona Y.} and Zhengming Chen and Liming Li and Sylvia Wassertheil-Smoller and Yunxuan Jiang and Chao Tian and Martin, {Nicholas G.} and Mitchell, {Brittany L.} and Byrne, {Enda M.} and Swapnil Awasthi and Coleman, {Jonathan R.I.} and Stephan Ripke and Tamar Sofer and Walters, {Robin G.} and McIntosh, {Andrew M.} and Renato Polimanti and Dunn, {Erin C.} and Stein, {Murray B.} and Joel Gelernter and Lewis, {Cathryn M.} and Karoline Kuchenbaecker",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

doi = "10.1038/s41588-023-01596-4",

language = "English",

volume = "56",

pages = "222–233",

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T1 - Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference

AU - Meng, Xiangrui

AU - Navoly, Georgina

AU - Giannakopoulou, Olga

AU - Levey, Daniel F.

AU - Koller, Dora

AU - Pathak, Gita A.

AU - Koen, Nastassja

AU - Lin, Kuang

AU - Adams, Mark J.

AU - Rentería, Miguel E.

AU - Feng, Yanzhe

AU - Gaziano, J. Michael

AU - Stein, Dan J.

AU - Zar, Heather J.

AU - Campbell, Megan L.

AU - van Heel, David A.

AU - Trivedi, Bhavi

AU - Finer, Sarah

AU - McQuillin, Andrew

AU - Bass, Nick

AU - Chundru, V. Kartik

AU - Martin, Hilary C.

AU - Huang, Qin Qin

AU - Valkovskaya, Maria

AU - Chu, Chia Yi

AU - Kanjira, Susan

AU - Kuo, Po Hsiu

AU - Chen, Hsi Chung

AU - Tsai, Shih Jen

AU - Liu, Yu Li

AU - Kendler, Kenneth S.

AU - Peterson, Roseann E.

AU - Cai, Na

AU - Fang, Yu

AU - Sen, Srijan

AU - Scott, Laura J.

AU - Burmeister, Margit

AU - Loos, Ruth J.F.

AU - Preuss, Michael H.

AU - Actkins, Ky’Era E.V.

AU - Davis, Lea K.

AU - Uddin, Monica

AU - Wani, Agaz H.

AU - Wildman, Derek E.

AU - Aiello, Allison E.

AU - Ursano, Robert J.

AU - Kessler, Ronald C.

AU - Kanai, Masahiro

AU - Okada, Yukinori

AU - Sakaue, Saori

AU - Rabinowitz, Jill A.

AU - Maher, Brion S.

AU - Uhl, George

AU - Eaton, William

AU - Cruz-Fuentes, Carlos S.

AU - Martinez-Levy, Gabriela A.

AU - Campos, Adrian I.

AU - Millwood, Iona Y.

AU - Chen, Zhengming

AU - Li, Liming

AU - Wassertheil-Smoller, Sylvia

AU - Jiang, Yunxuan

AU - Tian, Chao

AU - Martin, Nicholas G.

AU - Mitchell, Brittany L.

AU - Byrne, Enda M.

AU - Awasthi, Swapnil

AU - Coleman, Jonathan R.I.

AU - Ripke, Stephan

AU - Sofer, Tamar

AU - Walters, Robin G.

AU - McIntosh, Andrew M.

AU - Polimanti, Renato

AU - Dunn, Erin C.

AU - Stein, Murray B.

AU - Gelernter, Joel

AU - Lewis, Cathryn M.

AU - Kuchenbaecker, Karoline

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-023-01596-4

DO - 10.1038/s41588-023-01596-4

M3 - Journal article

C2 - 38177345

AN - SCOPUS:85181441322

SN - 1061-4036

VL - 56

SP - 222

EP - 233

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -