Genetic Risk and High Burden of Depression and Suicide in the Maya‐Mestizo Population of Yucatán, México

Major depression and suicide are critical public health concerns, particularly in underrepresented populations with unique genetic and sociocultural contexts. The Maya-mestizo population presents the highest suicide rates in the country but remains understudied in psychiatric genetics. This study evaluated the association between three genetic variants, rs7305115 (TPH2), rs6265 (BDNF), and rs2428707 (HTR2C), and the presence of major depression, melancholic subtype, and suicide risk in Maya-mestizo adults. A total of 598 participants were recruited from urban and rural areas. Psychiatric evaluations were performed using the MINI 5.0 (DSM-IV), and functional status was assessed with the Karnofsky scale. Genotyping was performed with TaqMan assays, and ancestry was confirmed with ancestry-informative markers. Analyses included Hardy-Weinberg equilibrium testing and logistic regression models adjusted for sex and included age, body mass index, Karnofsky performance scale score, and sociodemographic variables as covariates. The prevalence of major depression was 38.9%, while suicide risk reached 24.7%. The rs2428707 variant of HTR2C was significantly associated with major depression (OR 2.31, 95% CI 1.03-5.18, p = 0.041). Variants in TPH2 and BDNF were associated with the melancholic subtype. No statistically significant associations were found with suicide risk, though overlap with depressive phenotypes suggests shared vulnerability. This first report of psychiatric genetics in the Maya-mestizo population highlights the need for culturally and genetically tailored interventions.