Genome-wide assessment identifies novel runs of homozygosity linked to Parkinson’s disease etiology across diverse ancestral populations

We conducted the first large-scale, multi-ancestral investigation of Parkinson’s disease (PD) to examine the impact of genome-wide homozygosity on disease risk and age at onset. Using genotyping, imputed, and whole-genome sequencing (WGS) data from 16,599 PD cases and 13,585 controls across nine ancestral populations from the Global Parkinson’s Genetics Program, we aimed to identify novel regions of homozygosity contributing to PD heritability. Our findings suggest that ROH regions contribute to PD heritability in a global context, with a portion attributed to recessive allelic architecture. We developed an open-science framework for unbiased homozygosity mapping. Future studies should use larger, diverse cohorts and WGS data to uncover rare recessive variants linked to PD susceptibility.