The Genetic Architecture of Depression in Individuals of East Asian Ancestry: A Genome-Wide Association Study.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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, 23andMe Research Team, China Kadoorie Biobank Collaborative Group, and Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Аннотация
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.