Genetic variation associated with depression in Latin American populations: a systematic review of single-nucleotide...

Depression is a significant global health burden, with low- and middle-income countries disproportionately affected due to stigma, limited mental health resources, and imprecise diagnosis and treatment. In Latin America, reliance on non-specialized care further contributes to heterogeneous clinical outcomes. Although personalized medicine offers opportunities to improve depression management, genetic research has largely underrepresented Latin American populations, limiting understanding of ancestry-specific risk and treatment response.

This PRISMA 2020-compliant systematic review identified clinical studies assessing single-nucleotide polymorphisms in individuals of Latin American ancestry with depression through searches of PubMed, Web of Science, and EBSCO. Methodological quality was assessed, and findings were synthesized narratively due to substantial heterogeneity across studies.

Forty-five studies encompassing 26 cohorts (15 from Mexico, 9 from the United States, 1 from Brazil, and 1 from Peru) reported 306 variants, of which 14 were replicated across at least two independent cohorts. Variants in SLC6A4 (rs25531) and COMT (rs4680) were the most consistently reported. Low-expression rs25531 alleles were uncommon in Mexican and Mexican-American populations but more frequent among individuals with African ancestry. The COMT Met allele was repeatedly associated with greater symptom severity, increased suicide risk, and poorer response to selective serotonin reuptake inhibitors. Additional variants in TPH2, APOE, and BDNF showed ancestry- and context-dependent associations.

Despite limitations preventing meta-analysis, this review identifies both shared and population-specific genetic factors associated with depression in Latin American populations, highlighting the need for systematic and inclusive psychiatric genetics research to support the development of personalized interventions in underrepresented and resource-limited settings..