Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21.
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.
26 references, click to expand
-
The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts.Neurobiol Dis. 2007 Mar;25(3):561-70 PMID: 17174556
-
Genomic architecture of human 17q21 linked to frontotemporal dementia uncovers a highly homologous family of low-copy repeats in the tau region.Hum Mol Genet. 2005 Jul 1;14(13):1753-62 PMID: 15888485
-
A common LRRK2 mutation in idiopathic Parkinson's disease.Lancet. 2005 Jan 29-Feb 4;365(9457):415-6 PMID: 15680457
-
Multiple regions of alpha-synuclein are associated with Parkinson's disease.Ann Neurol. 2005 Apr;57(4):535-41 PMID: 15786467
-
Genome-wide association study reveals genetic risk underlying Parkinson's disease.Nat Genet. 2009 Dec;41(12):1308-12 PMID: 19915575
-
Evolutionary toggling of the MAPT 17q21.31 inversion region.Nat Genet. 2008 Sep;40(9):1076-83 PMID: 19165922
-
A flexible and accurate genotype imputation method for the next generation of genome-wide association studies.PLoS Genet. 2009 Jun;5(6):e1000529 PMID: 19543373
-
Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease.Nat Genet. 2009 Dec;41(12):1303-7 PMID: 19915576
-
Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4 PMID: 1564476
-
The tau H2 haplotype is almost exclusively Caucasian in origin.Neurosci Lett. 2004 Oct 21;369(3):183-5 PMID: 15464261
-
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
-
The distribution and most recent common ancestor of the 17q21 inversion in humans.Am J Hum Genet. 2010 Feb 12;86(2):161-71 PMID: 20116045
-
Principal components analysis corrects for stratification in genome-wide association studies.Nat Genet. 2006 Aug;38(8):904-9 PMID: 16862161
-
Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration.J Med Genet. 2005 Nov;42(11):837-46 PMID: 15792962
-
Association of MAPT haplotype-tagging SNPs with sporadic Parkinson's disease.Neurobiol Aging. 2009 Sep;30(9):1477-82 PMID: 18162161
-
Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication.Neurology. 2007 Mar 20;68(12):916-22 PMID: 17251522
-
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.Nature. 2010 Apr 1;464(7289):713-20 PMID: 20360734
-
The structure of the tau haplotype in controls and in progressive supranuclear palsy.Hum Mol Genet. 2004 Jun 15;13(12):1267-74 PMID: 15115761
-
alpha-Synuclein locus triplication causes Parkinson's disease.Science. 2003 Oct 31;302(5646):841 PMID: 14593171
-
Detecting gene-gene interactions that underlie human diseases.Nat Rev Genet. 2009 Jun;10(6):392-404 PMID: 19434077
-
Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease.Ann Hum Genet. 2010 Mar;74(2):97-109 PMID: 20070850
-
A genotype calling algorithm for the Illumina BeadArray platform.Bioinformatics. 2007 Oct 15;23(20):2741-6 PMID: 17846035
-
PLINK: a tool set for whole-genome association and population-based linkage analyses.Am J Hum Genet. 2007 Sep;81(3):559-75 PMID: 17701901
-
A common inversion under selection in Europeans.Nat Genet. 2005 Feb;37(2):129-37 PMID: 15654335
-
A new multipoint method for genome-wide association studies by imputation of genotypes.Nat Genet. 2007 Jul;39(7):906-13 PMID: 17572673
-
Different MAPT haplotypes are associated with Parkinson's disease and progressive supranuclear palsy.Neurobiol Aging. 2011 Mar;32(3):547.e11-6 PMID: 19879020
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