Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Jonggeol Jeffrey Kim; Dan Vitale; Diego Véliz Otani; Michelle Mulan Lian; Karl Heilbron; Hirotaka Iwaki; Julie Lake; Caroline Warly Solsberg; Hampton Leonard; Mary B Makarious; Eng-King Tan; Andrew B Singleton; Sara Bandres-Ciga; Alastair J Noyce; Cornelis Blauwendraat; Mike A Nalls; Jia Nee Foo; Ignacio Mata; Sulev Koks; 23andMe Research Team

doi:10.1038/s41588-023-01584-8

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Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Journal article

Open access

Peer reviewed

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Jonggeol Jeffrey Kim, Dan Vitale, Diego Véliz Otani, Michelle Mulan Lian, Karl Heilbron, Hirotaka Iwaki, Julie Lake, Caroline Warly Solsberg, Hampton Leonard, Mary B Makarious, …

Nature genetics, Vol.56, pp.27-36

2023

DOI: https://doi.org/10.1038/s41588-023-01584-8

PMID: 38155330

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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.

Details

Title: Multi-ancestry genome-wide association meta-analysis of Parkinson's disease
Authors/Creators: Jonggeol Jeffrey Kim - Queen Mary University of London
Dan Vitale - Data Tecnica International (United States)
Diego Véliz Otani - University of Maryland, Baltimore
Michelle Mulan Lian - Nanyang Technological University
Karl Heilbron - 23andMe (United States)
Hirotaka Iwaki - Data Tecnica International (United States)
Julie Lake - National Institute on Aging
Caroline Warly Solsberg - Memory and Aging Center, UCSF, San Francisco, CA, USA
Hampton Leonard - Data Tecnica International (United States)
Mary B Makarious - University of California, San Francisco
Eng-King Tan - Duke-NUS Medical School
Andrew B Singleton - National Institute on Aging
Sara Bandres-Ciga - National Institute of Neurological Disorders and Stroke
Alastair J Noyce - Queen Mary University of London
Cornelis Blauwendraat - National Institute of Neurological Disorders and Stroke
Mike A Nalls - Data Tecnica International (United States)
Jia Nee Foo - Nanyang Technological University
Ignacio Mata - Cleveland Clinic Lerner College of Medicine
Sulev Koks - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
23andMe Research Team
Publication Details: Nature genetics, Vol.56, pp.27-36
Publisher: Springer Nature
Grant note: ZIA AG000949 / Intramural NIH HHS
Identifiers: 991005625168107891
Copyright: This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023
Murdoch Affiliation: Murdoch University; Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article
Note: Sulev Koks appears courtesy of the the Global Parkinson’s Genetics Program (GP2)

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