Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21

• Published in: Human molecular genetics 2011-01, Vol.20 (2), p.345-353
• Main Authors: Spencer, Chris C A, Plagnol, Vincent, Strange, Amy, Gardner, Michelle, Paisan-Ruiz, Coro, Band, Gavin, Barker, Roger A, Bellenguez, Celine, Bhatia, Kailash, Blackburn, Hannah, Blackwell, Jennie M, Bramon, Elvira, Brown, Martin A, Brown, Matthew A, Burn, David, Casas, Juan-Pablo, Chinnery, Patrick F, Clarke, Carl E, Corvin, Aiden, Craddock, Nicholas, Deloukas, Panos, Edkins, Sarah, Evans, Jonathan, Freeman, Colin, Gray, Emma, Hardy, John, Hudson, Gavin, Hunt, Sarah, Jankowski, Janusz, Langford, Cordelia, Lees, Andrew J, Markus, Hugh S, Mathew, Christopher G, McCarthy, Mark I, Morrison, Karen E, Palmer, Colin N A, Pearson, Justin P, Peltonen, Leena, Pirinen, Matti, Plomin, Robert, Potter, Simon, Rautanen, Anna, Sawcer, Stephen J, Su, Zhan, Trembath, Richard C, Viswanathan, Ananth C, Williams, Nigel W, Morris, Huw R, Donnelly, Peter, Wood, Nicholas W
• Format: Article
• Language: English
• Subjects: Age of Onset; alpha-Synuclein - genetics; Biological and medical sciences; Case-Control Studies; Chromosomes, Human, Pair 17 - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Haplotypes; Humans; Medical sciences; Molecular and cellular biology; Neurology; Parkinson Disease - genetics; Polymorphism, Single Nucleotide; Sample Size; Whites
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddq469

We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P< 10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P< 10(-10)) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.