Genetic variants associated with idiopathic Parkinson's disease in Latin America: A systematic review

Idiopathic Parkinson's disease (PD) constitutes a complex trait influenced by genetic, environmental, and lifestyle factors, with an estimated heritability of nearly 30%. However, a large proportion of the heritable variation linked to PD remains uncertain, partly due to ancestral bias. Expanding research into Hispanic populations can contribute to address this gap. To review the evidence of genetic variants associated with idiopathic PD in Latin America. A PRISMA-compliant systematic review was conducted in MEDLINE, EMBASE and LILACS, compiling studies published up to February 7, 2025. Nineteen case-control studies were included. Two hypothesis-free studies identified rs525496 near H2BW1 as a protective factor and rs356182 in SNCA as a risk factor through XWAS and GWAS, respectively. Seventeen hypothesis-driven studies examined over three hundred variants, identifying nineteen genetic markers; risk factors included one INDEL in NR4A2, CNV burdens in PRKN, SNCA, and PLA2G6, along with fourteen variants in six loci including GBA, APOEε4, MTHFR, LRRK2, and SNCA. Three SNPs in the PICALM, ALDH1A1, and APOE-ε3 loci were identified as protective factors. Additionally, six SNCA variant haplotypes appear to increase PD risk, while two NR4A2 INDELs haplotypes showed mixed effects. This review summarized genetic loci associated with idiopathic PD in Latin American populations evidencing an overlap with European findings as well as novel loci, although awaiting replication and validation. These observations contribute to the understanding of genetic configuration of the disease and highlight the need for further genomic research in underrepresented groups that include local ancestry analysis within admixed cohorts to guide development of personalized treatments and population-specific interventions.