Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease

We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significant; these and six additional previously reported loci were then tested in an i...

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Detalles Bibliográficos
Autores principales: Nalls, Mike A, Pankratz, Nathan, Lill, Christina M., Do, Chuong B, Hernandez, Dena G., Saad, Mohamad, DeStefano, Anita L., Kara, Eleanna, Bras, Jose, Sharma, Manu, Schulte, Claudia, Keller, Margaux F., Arepalli, Sampath, Letson, Christopher, Edsall, Connor, Stefansson, Hreinn, Liu, Xinmin, Pliner, Hannah, Lee, Joseph H., Cheng, Rong, Ikram, M. Arfan, Ioannidis, John P.A., Hadjigeorgiou, Georgios M., Bis, Joshua C., Martinez, Maria, Perlmutter, Joel S., Goate, Alison, Marder, Karen, Fiske, Brian, Sutherland, Margaret, Xiromerisiou, Georgia, Myers, Richard H., Clark, Lorraine N, Stefansson, Kari, Hardy, John A., Heutink, Peter, Chen, Honglei, Wood, Nicholas W., Houlden, Henry, Payami, Haydeh, Brice, Alexis, Scott, William K, Gasser, Thomas, Bertram, Lars, Eriksson, Nicholas, Foroud, Tatiana, Singleton, Andrew B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146673/
https://www.ncbi.nlm.nih.gov/pubmed/25064009
http://dx.doi.org/10.1038/ng.3043
Descripción
Sumario:We conducted a meta analysis of Parkinson’s disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as genome-wide significant; these and six additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 novel loci. Conditional analyses within loci show four loci including GBA, GAK/DGKQ, SNCA, and HLA contain a secondary independent risk variant. In total we identified and replicated 28 independent risk variants for Parkinson disease across 24 loci. While the effect of each individual locus is small, a risk profile analysis revealed a substantial cummulative risk in a comparison highest versus lowest quintiles of genetic risk (OR=3.31, 95% CI: 2.55, 4.30; p-value = 2×10(−16)). We also show 6 risk loci associated with proximal gene expression or DNA methylation.

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