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The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study

IMPORTANCE: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. OBJECTIVE: To inve...

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Autores principales: Giannakopoulou, Olga, Lin, Kuang, Meng, Xiangrui, Su, Mei-Hsin, Kuo, Po-Hsiu, Peterson, Roseann E., Awasthi, Swapnil, Moscati, Arden, Coleman, Jonathan R. I., Bass, Nick, Millwood, Iona Y., Chen, Yiping, Chen, Zhengming, Chen, Hsi-Chung, Lu, Mong-Liang, Huang, Ming-Chyi, Chen, Chun-Hsin, Stahl, Eli A., Loos, Ruth J. F., Mullins, Niamh, Ursano, Robert J., Kessler, Ronald C., Stein, Murray B., Sen, Srijan, Scott, Laura J., Burmeister, Margit, Fang, Yu, Tyrrell, Jess, Jiang, Yunxuan, Tian, Chao, McIntosh, Andrew M., Ripke, Stephan, Dunn, Erin C., Kendler, Kenneth S., Walters, Robin G., Lewis, Cathryn M., Kuchenbaecker, Karoline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482304/
https://www.ncbi.nlm.nih.gov/pubmed/34586374
http://dx.doi.org/10.1001/jamapsychiatry.2021.2099
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author Giannakopoulou, Olga
Lin, Kuang
Meng, Xiangrui
Su, Mei-Hsin
Kuo, Po-Hsiu
Peterson, Roseann E.
Awasthi, Swapnil
Moscati, Arden
Coleman, Jonathan R. I.
Bass, Nick
Millwood, Iona Y.
Chen, Yiping
Chen, Zhengming
Chen, Hsi-Chung
Lu, Mong-Liang
Huang, Ming-Chyi
Chen, Chun-Hsin
Stahl, Eli A.
Loos, Ruth J. F.
Mullins, Niamh
Ursano, Robert J.
Kessler, Ronald C.
Stein, Murray B.
Sen, Srijan
Scott, Laura J.
Burmeister, Margit
Fang, Yu
Tyrrell, Jess
Jiang, Yunxuan
Tian, Chao
McIntosh, Andrew M.
Ripke, Stephan
Dunn, Erin C.
Kendler, Kenneth S.
Walters, Robin G.
Lewis, Cathryn M.
Kuchenbaecker, Karoline
author_facet Giannakopoulou, Olga
Lin, Kuang
Meng, Xiangrui
Su, Mei-Hsin
Kuo, Po-Hsiu
Peterson, Roseann E.
Awasthi, Swapnil
Moscati, Arden
Coleman, Jonathan R. I.
Bass, Nick
Millwood, Iona Y.
Chen, Yiping
Chen, Zhengming
Chen, Hsi-Chung
Lu, Mong-Liang
Huang, Ming-Chyi
Chen, Chun-Hsin
Stahl, Eli A.
Loos, Ruth J. F.
Mullins, Niamh
Ursano, Robert J.
Kessler, Ronald C.
Stein, Murray B.
Sen, Srijan
Scott, Laura J.
Burmeister, Margit
Fang, Yu
Tyrrell, Jess
Jiang, Yunxuan
Tian, Chao
McIntosh, Andrew M.
Ripke, Stephan
Dunn, Erin C.
Kendler, Kenneth S.
Walters, Robin G.
Lewis, Cathryn M.
Kuchenbaecker, Karoline
author_sort Giannakopoulou, Olga
collection PubMed
description IMPORTANCE: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. OBJECTIVE: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. EXPOSURES: Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts. MAIN OUTCOMES AND MEASURES: Depression status was defined based on health records and self-report questionnaires. RESULTS: There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = −0.018, SE = 0.003, P = 4.43x10(−8)) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10(−9) for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = −0.003, SE = 0.005, P = .53 for rs4656484 and β = −0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = −0.212, SE = 0.084), contrary to findings for individuals of European descent. CONCLUSIONS AND RELEVANCE: These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping.
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spelling pubmed-84823042021-10-08 The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study Giannakopoulou, Olga Lin, Kuang Meng, Xiangrui Su, Mei-Hsin Kuo, Po-Hsiu Peterson, Roseann E. Awasthi, Swapnil Moscati, Arden Coleman, Jonathan R. I. Bass, Nick Millwood, Iona Y. Chen, Yiping Chen, Zhengming Chen, Hsi-Chung Lu, Mong-Liang Huang, Ming-Chyi Chen, Chun-Hsin Stahl, Eli A. Loos, Ruth J. F. Mullins, Niamh Ursano, Robert J. Kessler, Ronald C. Stein, Murray B. Sen, Srijan Scott, Laura J. Burmeister, Margit Fang, Yu Tyrrell, Jess Jiang, Yunxuan Tian, Chao McIntosh, Andrew M. Ripke, Stephan Dunn, Erin C. Kendler, Kenneth S. Walters, Robin G. Lewis, Cathryn M. Kuchenbaecker, Karoline JAMA Psychiatry Original Investigation IMPORTANCE: Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations. OBJECTIVE: To investigate the genetics of depression among individuals of East Asian and European descent living in different geographic locations, and with different outcome definitions for depression. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association analyses followed by meta-analysis, which included data from 9 cohort and case-control data sets comprising individuals with depression and control individuals of East Asian descent. This study was conducted between January 2019 and May 2021. EXPOSURES: Associations of genetic variants with depression risk were assessed using generalized linear mixed models and logistic regression. The results were combined across studies using fixed-effects meta-analyses. These were subsequently also meta-analyzed with the largest published GWAS for depression among individuals of European descent. Additional meta-analyses were carried out separately by outcome definition (clinical depression vs symptom-based depression) and region (East Asian countries vs Western countries) for East Asian ancestry cohorts. MAIN OUTCOMES AND MEASURES: Depression status was defined based on health records and self-report questionnaires. RESULTS: There were a total of 194 548 study participants (approximate mean age, 51.3 years; 62.8% women). Participants included 15 771 individuals with depression and 178 777 control individuals of East Asian descent. Five novel associations were identified, including 1 in the meta-analysis for broad depression among those of East Asian descent: rs4656484 (β = −0.018, SE = 0.003, P = 4.43x10(−8)) at 1q24.1. Another locus at 7p21.2 was associated in a meta-analysis restricted to geographically East Asian studies (β = 0.028, SE = 0.005, P = 6.48x10(−9) for rs10240457). The lead variants of these 2 novel loci were not associated with depression risk in European ancestry cohorts (β = −0.003, SE = 0.005, P = .53 for rs4656484 and β = −0.005, SE = 0.004, P = .28 for rs10240457). Only 11% of depression loci previously identified in individuals of European descent reached nominal significance levels in the individuals of East Asian descent. The transancestry genetic correlation between cohorts of East Asian and European descent for clinical depression was r = 0.413 (SE = 0.159). Clinical depression risk was negatively genetically correlated with body mass index in individuals of East Asian descent (r = −0.212, SE = 0.084), contrary to findings for individuals of European descent. CONCLUSIONS AND RELEVANCE: These results support caution against generalizing findings about depression risk factors across populations and highlight the need to increase the ancestral and geographic diversity of samples with consistent phenotyping. American Medical Association 2021-11 2021-09-29 /pmc/articles/PMC8482304/ /pubmed/34586374 http://dx.doi.org/10.1001/jamapsychiatry.2021.2099 Text en Copyright 2021 Giannakopoulou O et al. JAMA Psychiatry. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Giannakopoulou, Olga
Lin, Kuang
Meng, Xiangrui
Su, Mei-Hsin
Kuo, Po-Hsiu
Peterson, Roseann E.
Awasthi, Swapnil
Moscati, Arden
Coleman, Jonathan R. I.
Bass, Nick
Millwood, Iona Y.
Chen, Yiping
Chen, Zhengming
Chen, Hsi-Chung
Lu, Mong-Liang
Huang, Ming-Chyi
Chen, Chun-Hsin
Stahl, Eli A.
Loos, Ruth J. F.
Mullins, Niamh
Ursano, Robert J.
Kessler, Ronald C.
Stein, Murray B.
Sen, Srijan
Scott, Laura J.
Burmeister, Margit
Fang, Yu
Tyrrell, Jess
Jiang, Yunxuan
Tian, Chao
McIntosh, Andrew M.
Ripke, Stephan
Dunn, Erin C.
Kendler, Kenneth S.
Walters, Robin G.
Lewis, Cathryn M.
Kuchenbaecker, Karoline
The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study
title The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study
title_full The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study
title_fullStr The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study
title_full_unstemmed The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study
title_short The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study
title_sort genetic architecture of depression in individuals of east asian ancestry: a genome-wide association study
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482304/
https://www.ncbi.nlm.nih.gov/pubmed/34586374
http://dx.doi.org/10.1001/jamapsychiatry.2021.2099
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