The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.
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Author
Giannakopoulou, OlgaLin, 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
Journal title
JAMA psychiatryPublication Volume
78Publication Issue
11Publication Begin page
1258Publication End page
1269
Metadata
Show full item recordAbstract
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.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.
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.
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.
Depression status was defined based on health records and self-report questionnaires.
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.
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.
Citation
Giannakopoulou O, Lin K, Meng X, Su MH, Kuo PH, Peterson RE, Awasthi S, Moscati A, Coleman JRI, Bass N, Millwood IY, Chen Y, Chen Z, Chen HC, Lu ML, Huang MC, Chen CH, Stahl EA, Loos RJF, Mullins N, Ursano RJ, Kessler RC, Stein MB, Sen S, Scott LJ, Burmeister M, Fang Y, Tyrrell J, Jiang Y, Tian C, McIntosh AM, Ripke S, Dunn EC, Kendler KS, Walters RG, Lewis CM, Kuchenbaecker K; 23andMe Research Team, China Kadoorie Biobank Collaborative Group, and Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study. JAMA Psychiatry. 2021 Nov 1;78(11):1258-1269. doi: 10.1001/jamapsychiatry.2021.2099. PMID: 34586374; PMCID: PMC8482304.DOI
10.1001/jamapsychiatry.2021.2099ae974a485f413a2113503eed53cd6c53
10.1001/jamapsychiatry.2021.2099
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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International
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