TY - JOUR
T1 - The Genetic Architecture of Depression in Individuals of East Asian Ancestry
T2 - A Genome-Wide Association Study
AU - Giannakopoulou, Olga
AU - Lin, Kuang
AU - Meng, Xiangrui
AU - Su, Mei-Hsin
AU - Kuo, Po-Hsiu
AU - Peterson, Roseann E
AU - Awasthi, Swapnil
AU - Moscati, Arden
AU - Coleman, Jonathan R I
AU - Bass, Nick
AU - Millwood, Iona Y
AU - Chen, Yiping
AU - Chen, Zhengming
AU - Chen, Hsi-Chung
AU - Lu, Mong-Liang
AU - Huang, Ming-Chyi
AU - Chen, Chun-Hsin
AU - Stahl, Eli A
AU - Loos, Ruth J F
AU - Mullins, Niamh
AU - Ursano, Robert J
AU - Kessler, Ronald C
AU - Stein, Murray B
AU - Sen, Srijan
AU - Scott, Laura J
AU - Burmeister, Margit
AU - Fang, Yu
AU - Tyrrell, Jess
AU - Jiang, Yunxuan
AU - Tian, Chao
AU - McIntosh, Andrew M
AU - Ripke, Stephan
AU - Dunn, Erin C
AU - Kendler, Kenneth S
AU - Walters, Robin G
AU - Lewis, Cathryn M
AU - Kuchenbaecker, Karoline
AU - 23andMe Research Team, China Kadoorie Biobank Collaborative Group, and Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
A2 - Hansen, Thomas Folkmann
A2 - Werge, Thomas Mears
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - Adult
KW - Asians/ethnology
KW - Depression/ethnology
KW - Depressive Disorder/ethnology
KW - Far East/ethnology
KW - Female
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Middle Aged
KW - Whites/genetics
UR - http://www.scopus.com/inward/record.url?scp=85116536140&partnerID=8YFLogxK
U2 - 10.1001/jamapsychiatry.2021.2099
DO - 10.1001/jamapsychiatry.2021.2099
M3 - Journal article
C2 - 34586374
SN - 2168-622X
VL - 78
SP - 1258
EP - 1269
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 11
ER -