rs11650438 (PIGL): Parkinson's Disease Risk Variant

Key takeaways

• rs11650438 near PIGL is one of 12 newly identified potentially novel Parkinson's disease risk loci from a multi-ancestry study of nearly 2.5 million people
• The finding spans four ancestral populations (European, East Asian, Latin American, and African), making it broader than most prior Parkinson's genetic studies
• This variant is linked to reduced expression of CENPV in the caudate basal ganglia, a brain region heavily affected in Parkinson's disease
• The locus is classified as "potentially novel" and requires independent replication to be considered confirmed

What the research says A large multi-ancestry genome-wide association study (GWAS) meta-analysis of Parkinson's disease (PD), drawing on 49,049 cases, 18,618 proxy cases (first-degree relatives of PD patients, counted as indirect family-history evidence), and 2,458,063 neurologically healthy controls across European, East Asian, Latin American, and African populations, identified the PIGL gene region as one of 12 potentially novel PD risk loci among 78 total genome-wide significant signals. By pairing GWAS results with expression quantitative trait locus (eQTL) data, a type of data that connects genetic variants to changes in how actively a gene is expressed in tissue, the study nominated 25 putative risk genes across all novel loci whose expression levels are associated with PD susceptibility. The per-allele effect size for rs11650438 specifically was not recoverable from the provided study text.

Reported associations

• Parkinson's disease: rs11650438 identified as one of 12 potentially novel risk loci in a multi-ancestry meta-analysis (49,049 cases, 18,618 proxy cases, 2,458,063 controls); the per-allele effect size for this locus was not available in the provided study excerpt

Evidence quality The PD association rests on a well-powered, multi-ancestry meta-analysis totaling more than 2.5 million individuals, using both a random-effects model and MR-MEGA (a statistical method designed to detect genetic signals that vary across ancestries by accounting for population-level genetic differences). This locus is one of 12 described as "potentially novel," a term the study authors use to distinguish new discoveries from the 66 known PD loci also detected. These 12 loci have not yet been independently replicated in separate cohorts. The overall study applied a Bonferroni-adjusted genome-wide significance threshold of P < 5 x 10-9. No conflicting findings were identified in the provided evidence.

Tissue-specific expression effects

• CENPV: reduced expression in tibial artery, in the caudate nucleus of the basal ganglia (a brain region central to Parkinson's disease), and in the aorta GTEx Portal
• ADORA2B: reduced expression in thyroid, tibial artery, skeletal muscle, and the muscularis layer of the esophagus GTEx Portal
• ZSWIM7: reduced expression in skeletal muscle GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.