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 |
| Externally published | Yes |
ASJC Scopus subject areas
- Genetics
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In: Nature Genetics, Vol. 56, No. 1, 01.2024, p. 27-36.
Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
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AU - Vitale, Dan
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AU - Tung, Joyce Y.
AU - Wang, Xin
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AU - Weldon, Catherine H.
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AU - Kim, Yun Joong
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AU - Zweier, Christiane
AU - Tinkhauser, Gerd
AU - Krack, Paul
AU - Lin, Chin Hsien
AU - Wu, Hsiu Chuan
AU - Kung, Pin Jui
AU - Wu, Ruey Meei
AU - Wu, Yihru
AU - Amouri, Rim
AU - Sassi, Samia Ben
AU - Başak, A. Nazl
AU - Genc, Gencer
AU - Çakmak, Özgür Öztop
AU - Ertan, Sibel
AU - Martínez-Carrasco, Alejandro
AU - Schrag, Anette
AU - Schapira, Anthony
AU - Carroll, Camille
AU - Bale, Claire
AU - Grosset, Donald
AU - Stafford, Eleanor J.
AU - Houlden, Henry
AU - Morris, Huw R.
AU - Hardy, John
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AU - Shulman, Joshua
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AU - Louie, Naomi
AU - Mencacci, Niccolò Emanuele
AU - Albin, Roger
AU - Alcalay, Roy
AU - Walker, Ruth
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AU - Dumanis, Sonya
AU - Lubbe, Steven
AU - Xie, Tao
AU - Foroud, Tatiana
AU - Beach, Thomas
AU - Sherer, Todd
AU - Song, Yeajin
AU - Nguyen, Duan
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N1 - Publisher Copyright: © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85180652227&partnerID=8YFLogxK
U2 - 10.1038/s41588-023-01584-8
DO - 10.1038/s41588-023-01584-8
M3 - Article
C2 - 38155330
AN - SCOPUS:85180652227
SN - 1061-4036
VL - 56
SP - 27
EP - 36
JO - Nature Genetics
JF - Nature Genetics
IS - 1
ER -