Genome-wide meta-analysis of short-tandem repeats for Parkinson's disease risk

Idiopathic Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease and is determined by a combination of genetic and environmental risk factors. The to date largest genome-wide association study (GWAS) on single nucleotide polymorphisms (SNPs) by Nalls at al., 2019, reported 90 SNPs that were independently associated with PD risk. However, common SNPs account only for 16-36% of the total genetic heritability of the disease suggesting that other genetic variants play a role in PD susceptibility. One example of previously understudied genetic variants are short-tandem repeats (STR, also known as microsatellites), i.e., repeating sequence motifs in the human genome of 1-6 nucleotides in length. Thus, in this study, we performed a GWAS on imputed STRs in a large PD case-control dataset (n=4,757), and meta-analyzed these data with those from a previous study of the International PD Genetics Consortium (Bustos et al., 2023) resulting in a total sample size of  43,844 PD cases and controls. Thus, in this study, we performed a GWAS on imputed STRs in a large PD case-control dataset (n=4,757) from the US (the PEG and a GHC-based study) and Denmark (PASIDA).