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.
DESIGN: Cross-sectional analysis was carried out using the first wave data from MELoR which is a longitudinal study.
SETTING: Urban community dwellers in a middle-income South East Asian country.
PARTICIPANTS: 1565 participants aged ≥55 years were selected by simple random sampling from the electoral rolls of three parliamentary constituencies.
OUTCOME MEASURES: Consenting participants from the MELoR study were asked the question 'Have you fallen down in the past 12 months?' during their computer-assisted home-based interviews. Logistic regression analyses were conducted to compare the prevalence of falls among various ethnic groups.
RESULTS: The overall estimated prevalence of falls for individuals aged 55 years and over adjusted to the population of Kuala Lumpur was 18.9%. The estimated prevalence of falls for the three ethnic populations of Malays, Chinese and Indian aged 55 years and over was 16.2%, 19.4% and 23.8%, respectively. Following adjustment for ethnic discrepancies in age, gender, marital status and education attainment, the Indian ethnicity remained an independent predictor of falls in our population (relative risk=1.45, 95% CI 1.08 to 1.85).
CONCLUSION: The prevalence of falls in this study is comparable to other previous Asian studies, but appears lower than Western studies. The predisposition of the Indian ethnic group to falls has not been previously reported. Further studies may be needed to elucidate the causes for the ethnic differences in fall prevalence.