Selected SNPs in the BDNF and DRD2 genes and their associations with antipsychotic-induced weight gain in a Sri Lankan cohort

Abstract

Antipsychotic-induced weight gain (AIWG) is a prevalent and clinically significant side effect that compromises treatment adherence and exacerbates metabolic health risks in individuals receiving antipsychotic medication. While several genetic variants have been implicated in modulating AIWG risk, their population-specific pharmacogenetic architecture remains underexplored in South Asian settings. This study investigated the associations of four SNPs from two genes, rs6265 (BDNF gene), rs1799732, rs1800497, and rs4436578 (DRD2 gene), with AIWG in a Sri Lankan schizophrenia cohort (n = 304). SNPs were genotyped via competitive amplification of differentially melting amplicons (CADMA) with high-resolution melt analysis (HRMA) and validated via the MassARRAY System. Statistical analyses, including association, and interaction analyses, were performed using the SNPstats online tool. Genotyping and association analyses revealed marginal association of rs6265 (T allele) with weight gain (OR = 3.25, 95 % CI: 0.85–12.51, p = 0.068), while a protective role for the A allele of rs1800497 was also identified (OR = 0.58, 95 % CI: 0.36–0.91, p = 0.018). This study highlights the utility of integrating genetic screening into psychiatric care to guide personalized treatment strategies and mitigate adverse drug effects in underrepresented populations.