A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson's disease
- Holmans, P.
- Moskvina, V.
- Jones, L.
- Sharma, M.
- Vedernikov, A.
- Buchel, F.
- Sadd, M.
- Bras, J.M.
- Bettella, F.
- Nicolaou, N.
- Simon-Sanchez, J.
- Mittag, F.
- Gibbs, J.R.
- Schulte, C.
- Durr, A.
- Guerreiro, R.
- Hernandez, D.
- Brice, A.
- Stefansson, H.
- Majamaa, K.
- Gasser, T.
- Heutink, P.
- Wood, N.W.
- Martinez, M.
- Singleton, A.B.
- Nalls, M. A.
- Hardy, J.
- Morris, H.R.
- Williams, N.M.
- Arepalli, S.
- Barker, R.
- Barrett, J.
- Ben-Shlomo, Y.
- Berendse, H.W.
- Berg, D.
- Bhatia, K.
- de Bie, R.M.A.
- Biffi, A.
- Bloem, B.
- Bochdanovits, Z.
- Bonin, M.
- Brockmann, K.
- Brooks, J.
- Burn, D.J.
- Charlesworth, G.
- Chen, H.
- Chinnery, P. F.
- Chong, S.
- Clarke, C. E.
- Cookson, M.R.
- Cooper, J.M.
- Corvol, J.-C.
- Counsell, C.
- Damier, P.
- Dartigues, J.F.
- Deloukas, P.
- Deuschl, G.
- Dexter, D.T.
- van Dijk, K.D.
- Dillman, A.
- Durif, F.
- Edkins, S.
- Evans, J.R.
- Foltynie, T.
- Gao, J.
- Gardner, M.
- Goate, A.
- Gray, E.
- Gustafsson, O.
- Harris, C.
- Hernandez, D.G.
- van Hilten, J.J.
- Hofman, A.
- Hollenbeck, A.
- Holton, J.
- Hu, M.
- Huber, H.
- Hudson, G.
- Hunt, S.E.
- Huttenlocher, J.
- Illig, T.
- Langford, C.
- Lees, A.
- Lesage, S.
- Lichtner, P.
- Limousin, P.
- Lopez, G.
- Lorenz, D.
- McNeill, A.
- Moorby, C.
- Moore, M.
- Morris, H.
- Morrison, K.E.
- Mudanohwo, E.
- Nalls, M.A.
- Pearson, J.
- Perlmutter, J.S.
- Petursson, H.
- Plagnol, V.
- Pollak, P.
- Post, B.
- Potter, S.
- Ravina, B.
- Revesz, T.
- Riess, O.
- Rivadeneira, F.
- Rizzu, P.
- Ryten, M.
- Saad, M.
- Sawcer, S.
- Schapira, A.
- Scheffer, H.
- Shaw, K.
- Sheerin, U.-M.
- Shoulson, I.
- Sidransky, E.
- Smith, C.
- Stefansson, K.
- Steinberg, S.
- Stockton, J.D.
- Sveinbjornsdottir, S.
- Talbot, K.
- Tanner, C.M.
- Tashakkori-Ghanbaria, A.
- Tison, F.
- Trabzuni, D.
- Traynor, B.J.
- Uitterlinden, A.G.
- Velseboer, D.
- Vidailhet, M.
- Walker, R.
- van de Warrenburg, B.
- Wickremaratchi, M.
- Williams, N.
- Williams-Gray, C.H.
- Winder-Rhodes, S.
- Wood, N.
DOIAbstract
Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1–2% in people >60 and 3–4% in people >80. Genome-wide association (GWA) studies have now implicated significant evidence for association in at least 18 genomic regions. We have studied a large PD-meta analysis and identified a significant excess of SNPs (P < 1 × 10?16) that are associated with PD but fall short of the genome-wide significance threshold. This result was independent of variants at the 18 previously implicated regions and implies the presence of additional polygenic risk alleles. To understand how these loci increase risk of PD, we applied a pathway-based analysis, testing for biological functions that were significantly enriched f...
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