Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21.
UK Parkinson's Disease Consortium None., Wellcome Trust Case Control Consortium 2 None., Spencer CCA., Plagnol V., Strange A., Gardner M., Paisan-Ruiz C., Band G., Barker RA., Bellenguez C., Bhatia K., Blackburn H., Blackwell JM., Bramon E., Brown MA., Brown MA., Burn D., Casas J-P., Chinnery PF., Clarke CE., Corvin A., Craddock N., Deloukas P., Edkins S., Evans J., Freeman C., Gray E., Hardy J., Hudson G., Hunt S., Jankowski J., Langford C., Lees AJ., Markus HS., Mathew CG., McCarthy MI., Morrison KE., Palmer CNA., Pearson JP., Peltonen L., Pirinen M., Plomin R., Potter S., Rautanen A., Sawcer SJ., Su Z., Trembath RC., Viswanathan AC., Williams NW., Morris HR., Donnelly P., Wood NW.
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.