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

Autoria(s): Spencer, C. C.; 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, Matthew A; Burn, D.; Casas, J. P.; Chinnery, P. F.; Clarke, C. E.; 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, A. J.; Markus, H. S.; Mathew, C. G.; McCarthy, M. I.; Morrison, K. E.; Palmer, C. N.; Pearson, J. P.; Peltonen, L.; Pirinen, M.; Plomin, R.; Potter, S.; Rautanen, A.; Sawcer, S. J.; Su, Z.; Trembath, R. C.; Viswanathan, A. C.; Williams, N. W.; Morris, H. R.; Donnelly, P.; Wood, N. W.
Data(s)

2011
Resumo

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. © The Author 2010. Published by Oxford University Press.
Identificador

http://eprints.qut.edu.au/89356/
Publicador

Oxford University Press
Relação

DOI:10.1093/hmg/ddq469

Spencer, C. C., 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, Matthew A, Burn, D., Casas, J. P., Chinnery, P. F., Clarke, C. E., 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, A. J., Markus, H. S., Mathew, C. G., McCarthy, M. I., Morrison, K. E., Palmer, C. N., Pearson, J. P., Peltonen, L., Pirinen, M., Plomin, R., Potter, S., Rautanen, A., Sawcer, S. J., Su, Z., Trembath, R. C., Viswanathan, A. C., Williams, N. W., Morris, H. R., Donnelly, P., & Wood, N. W. (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), pp. 345-353.
Fonte

Faculty of Health; Institute of Health and Biomedical Innovation
Palavras-Chave #adult #aged #article #chromosome 17q #cohort analysis #controlled study #female #France #gene replication #genetic association #genetic variability #haplotype #human #major clinical study #male #onset age #Parkinson disease #priority journal #promoter region #risk factor #single nucleotide polymorphism #United Kingdom #Age of Onset #alpha-Synuclein #Case-Control Studies #Chromosomes #Human #Pair 17 #European Continental Ancestry Group #Genetic Predisposition to Disease #Genome-Wide Association Study #Haplotypes #Humans #Polymorphism #Single Nucleotide #Sample Size
Tipo

Journal Article
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