TY - JOUR
T1 - Common variants in PARK loci and related genes and Parkinson's disease
AU - Chung, Sun Ju
AU - Armasu, Sebastian M.
AU - Biernacka, Joanna M.
AU - Lesnick, Timothy G.
AU - Rider, David N.
AU - Lincoln, Sarah J.
AU - Ortolaza, Alexandra I.
AU - Farrer, Matthew J.
AU - Cunningham, Julie M.
AU - Rocca, Walter A.
AU - Maraganore, Demetrius M.
PY - 2011/2/1
Y1 - 2011/2/1
N2 - Rare mutations in PARK loci genes cause Parkinson's disease (PD) in some families and isolated populations. We investigated the association of common variants in PARK loci and related genes with PD susceptibility and age at onset in an outbred population. A total of 1,103 PD cases from the upper Midwest, USA, were individually matched to unaffected siblings (n = 654) or unrelated controls (n = 449) from the same region. Using a sequencing approach in 25 cases and 25 controls, single nucleotide polymorphisms (SNPs) in species-conserved regions of PARK loci and related genes were detected. We selected additional tag SNPs from the HapMap. We genotyped a total of 235 SNPs and two variable number tandem repeats in the ATP13A2, DJ1, LRRK1, LRRK2, MAPT, Omi/HtrA2, PARK2, PINK1, SNCA, SNCB, SNCG, SPR, and UCHL1 genes in all 2,206 subjects. Case-control analyses were performed to study association with PD susceptibility, while cases-only analyses were used to study association with age at onset. Only MAPT SNP rs2435200 was associated with PD susceptibility after correction for multiple testing (OR = 0.74, 95% CI = 0.64-0.86, uncorrected P < 0.0001, log additive model); however, 16 additional MAPT variants, seven SNCA variants, and one LRRK2, PARK2, and UCHL1 variants each had significant uncorrected P-values. There were no significant associations for age at onset after correction for multiple testing. Our results confirm the association of MAPT and SNCA genes with PD susceptibility but show limited association of other PARK loci and related genes with PD.
AB - Rare mutations in PARK loci genes cause Parkinson's disease (PD) in some families and isolated populations. We investigated the association of common variants in PARK loci and related genes with PD susceptibility and age at onset in an outbred population. A total of 1,103 PD cases from the upper Midwest, USA, were individually matched to unaffected siblings (n = 654) or unrelated controls (n = 449) from the same region. Using a sequencing approach in 25 cases and 25 controls, single nucleotide polymorphisms (SNPs) in species-conserved regions of PARK loci and related genes were detected. We selected additional tag SNPs from the HapMap. We genotyped a total of 235 SNPs and two variable number tandem repeats in the ATP13A2, DJ1, LRRK1, LRRK2, MAPT, Omi/HtrA2, PARK2, PINK1, SNCA, SNCB, SNCG, SPR, and UCHL1 genes in all 2,206 subjects. Case-control analyses were performed to study association with PD susceptibility, while cases-only analyses were used to study association with age at onset. Only MAPT SNP rs2435200 was associated with PD susceptibility after correction for multiple testing (OR = 0.74, 95% CI = 0.64-0.86, uncorrected P < 0.0001, log additive model); however, 16 additional MAPT variants, seven SNCA variants, and one LRRK2, PARK2, and UCHL1 variants each had significant uncorrected P-values. There were no significant associations for age at onset after correction for multiple testing. Our results confirm the association of MAPT and SNCA genes with PD susceptibility but show limited association of other PARK loci and related genes with PD.
KW - Age at onset of parkinson's disease
KW - Common genetic variants
KW - PARK loci genes
KW - Parkinson's disease
KW - Susceptibility to parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=79951474478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951474478&partnerID=8YFLogxK
U2 - 10.1002/mds.23376
DO - 10.1002/mds.23376
M3 - Article
C2 - 21412835
AN - SCOPUS:79951474478
VL - 26
SP - 280
EP - 288
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 2
ER -