Summary
A medRxiv preprint reports five genetic loci associated with age at Parkinson’s disease onset in a meta-analysis of 50,859 people with the disease. The findings include signals near SNCA, GBA1 and HIP1R, while the APOE association may reflect effects on longevity.
A medRxiv preprint reports five genetic loci associated with the age at which Parkinson’s disease (PD) begins, based on a genome-wide association study meta-analysis of 50,859 people with PD. The analysis found signals near SNCA and GBA1, replicated an earlier SNCA association, and nominated HIP1R and a region near FSCB as additional candidates. The authors also found an association at APOE, which they say may reflect the gene’s relationship with longevity rather than PD onset itself.
What the analysis found
The researchers combined data from the Global Parkinson’s Genetics Program, the International Parkinson’s Disease Genomics Consortium, UK Biobank, Fox Insight Genetics Study, FinnGen and deCODE Genetics. The study focused on age at onset among people who already had PD, rather than on genetic risk of developing the disease.
The preprint reports five genome-wide significant loci. At SNCA, it replicated an association at rs356182. At GBA1, it reports a genome-wide significant association at rs76763715 and an additional independent association at rs35777901. It nominates rs10847864 near HIP1R—a gene previously implicated in PD risk—and rs10083396, whose nearest annotated gene is FSCB, as new candidates associated with age at onset.
The authors also report a significant association at APOE, a known Alzheimer’s disease risk locus. Their analysis indicates that this signal may be driven by the effect of APOE genotype on longevity, independent of PD status. That distinction matters: an association with age at onset among people with PD need not reflect a biological process that directly changes when PD begins.
Why age at onset is a separate genetic question
A genome-wide association study (GWAS) tests whether genetic variants occur more often alongside a measured trait. In this study, the trait was age at onset, not disease occurrence. A variant associated with PD risk therefore need not also influence when symptoms begin, and a signal tied to age at onset does not by itself explain the mechanism behind that timing.
The findings point to some overlap between the genetics of PD risk and the genetics of onset timing, particularly around SNCA, GBA1 and HIP1R. The researchers say the newly nominated HIP1R and FSCB-region signals need functional follow-up. Such work could help determine how the associated regions relate to disease biology; the preprint itself reports genetic associations, not established causal mechanisms or clinical tests.
The study concerns European-ancestry populations, so its results do not establish that the same signals or effects apply across other ancestry groups. The work is posted as a preprint on medRxiv.