Chang, D;
Nalls, MA;
Hallgrímsdóttir, IB;
Hunkapiller, J;
van der Brug, M;
Cai, F;
Kerchner, GA;
... Graham, RR; + view all
(2017)
A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.
Nature Genetics
, 49
(10)
pp. 1511-1516.
10.1038/ng.3955.
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Abstract
Common variant genome-wide association studies (GWASs) have, to date, identified >24 risk loci for Parkinson's disease (PD). To discover additional loci, we carried out a GWAS comparing 6,476 PD cases with 302,042 controls, followed by a meta-analysis with a recent study of over 13,000 PD cases and 95,000 controls at 9,830 overlapping variants. We then tested 35 loci (P < 1 × 10−6) in a replication cohort of 5,851 cases and 5,866 controls. We identified 17 novel risk loci (P < 5 × 10−8) in a joint analysis of 26,035 cases and 403,190 controls. We used a neurocentric strategy to assign candidate risk genes to the loci. We identified protein-altering or cis–expression quantitative trait locus (cis-eQTL) variants in linkage disequilibrium with the index variant in 29 of the 41 PD loci. These results indicate a key role for autophagy and lysosomal biology in PD risk, and suggest potential new drug targets for PD.
| Type: | Article |
|---|---|
| Title: | A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ng.3955 |
| Publisher version: | http://dx.doi.org/10.1038/ng.3955 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Genome-wide association studies, Parkinson's disease |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10045138 |
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