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

Chris C A Spencer, Vincent Plagnol, Amy Strange, Michelle Gardner, Coro Paisan-Ruiz, Gavin Band, Roger A Barker, Celine Bellenguez, Kailash Bhatia, Hannah Blackburn, Jennie M Blackwell, Elvira Bramon, Martin A Brown, Matthew A Brown, David Burn, Juan-Pablo Casas, Patrick F Chinnery, Carl E Clarke, Aiden Corvin, Nicholas CraddockPanos Deloukas, Sarah Edkins, Jonathan Evans, Colin Freeman, Emma Gray, John Hardy, Gavin Hudson, Sarah Hunt, Janusz Jankowski, Cordelia Langford, Andrew J Lees, Hugh S Markus, Christopher G Mathew, Mark I McCarthy, Karen E Morrison, Colin N A Palmer, Justin P Pearson, Leena Peltonen, Matti Pirinen, Robert Plomin, Simon Potter, Anna Rautanen, Stephen J Sawcer, Zhan Su, Richard C Trembath, Ananth C Viswanathan, Nigel W Williams, Huw R Morris, Peter Donnelly, Nicholas W Wood, UK Parkinson's Disease Consortium

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    Abstract

    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.
    Original languageEnglish
    Pages (from-to)345-53
    Number of pages9
    JournalHuman Molecular Genetics
    Volume20
    Issue number2
    DOIs
    Publication statusPublished - 2011

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  • Cite this

    Spencer, C. C. A., Plagnol, V., Strange, A., Gardner, M., Paisan-Ruiz, C., Band, G., Barker, R. A., Bellenguez, C., Bhatia, K., Blackburn, H., Blackwell, J. M., Bramon, E., Brown, M. A., Brown, M. A., Burn, D., Casas, J-P., Chinnery, P. F., Clarke, C. E., Corvin, A., ... UK Parkinson's Disease Consortium (2011). Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21. Human Molecular Genetics, 20(2), 345-53. https://doi.org/10.1093/hmg/ddq469