A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
| Autor: | Quinn, JP, Billingsley, Kimberley, Chang, D, Nalls, MA, Hallgrímsdóttir, IB, Hunkapiller, J, van der Brug, M, Cai, F, International Parkinson's Disease Genomics Consortium, 23andMe Research Team, Kerchner, GA, Ayalon, G, Bingol, B, Sheng, M, Hinds, D, Behrens, TW, Singleton, AB, Bhangale, TR, Graham, RR |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Risk Linkage disequilibrium Genome-wide association study Disease Biology Quantitative trait locus Article Linkage Disequilibrium Antiparkinson Agents 03 medical and health sciences 0302 clinical medicine Genetics Autophagy Humans Genetic Predisposition to Disease Molecular Targeted Therapy Gene Genetic association Case-control study Parkinson Disease 030104 developmental biology Genetic Loci Meta-analysis Case-Control Studies Lysosomes 030217 neurology & neurosurgery Genome-Wide Association Study Transcription Factors |
| Zdroj: | Nature Genetics |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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