Abstract
Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 27-36 |
| Number of pages | 10 |
| Journal | Nature Genetics |
| Volume | 56 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2024 |
Funding
This work was supported by the following grants and institutions: Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging (NIA), NIH, Department of Health and Human Services (A.B.S., C.B. and M.A.N.); National Institute of Neurological Disorders and Stroke (project numbers ZO1 AG000535 and ZIA AG000949 to A.B.S., C.B. and M.A.N.) (grant number R01NS112499 to I.M.); Parkinson’s Foundation (Stanley Fahn Junior Faculty Award and an International Research Grants Program award to I.M.), Michael J Fox Foundation (to I.M. and A.J.N); Aligning Science Across Parkinson’s Global Parkinson’s Genetic Project (ASAP-GP2) (to I.M. and A.J.N); American Parkinson’s Disease Association (to I.M.); National Medical Research Council Singapore (Open Fund Large Collaborative Grant MOH-000207 to E.-K.T.) (Open Fund Individual Research Grant MOH-000559 to J.N.F.); and Singapore Ministry of Education Academic Research Fund (Tier 2 MOE-T2EP30220-0005 and Tier 3 MOE-MOET32020-0004 to J.N.F.). Participation in this project was part of a competitive contract awarded to Data Tecnica International by the NIH to support open science research. This research has been conducted using the UK Biobank Resource under Application Number 33601. We want to acknowledge the participants and investigators of FinnGen study. We thank the research participants and employees of 23andMe. Data used in the preparation of this article were obtained from Global Parkinson’s Genetics Program (GP2). GP2 is funded by the Aligning Science Against Parkinson’s (ASAP) initiative and implemented by the Michael J. Fox Foundation for Parkinson’s Research ( https://gp2.org ). For a complete list of GP2 members, see https://gp2.org . This work used the computational resources of the NIH HPC Biowulf cluster ( http://hpc.nih.gov ).
ASJC Scopus subject areas
- Genetics