TY - JOUR
T1 - Genomic determinants of motor and cognitive outcomes in Parkinson's disease
AU - Chung, Sun Ju
AU - Armasu, Sebastian M.
AU - Biernacka, Joanna M.
AU - Anderson, Kari J.
AU - Lesnick, Timothy G.
AU - Rider, David N.
AU - Cunningham, Julie M.
AU - Eric Ahlskog, J.
AU - Frigerio, Roberta
AU - Maraganore, Demetrius M.
N1 - Funding Information:
This paper was made possible by a grant from the National Institutes of Health (2R01ES10751) and from the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson’s Disease Solutions). Demetrius M. Maraganore, MD has licensed an invention to Alnylam Pharmaceuticals, Inc. regarding a method to treat Parkinson’s disease (unrelated to the work presented in this manuscript). He has received less than $20,000 in royalties.
PY - 2012/8
Y1 - 2012/8
N2 - Background: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). Objective: To identify common genetic variants associated with motor and cognitive outcomes in PD. Methods: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). Results: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10-6). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10-6). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. Conclusions: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.
AB - Background: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). Objective: To identify common genetic variants associated with motor and cognitive outcomes in PD. Methods: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). Results: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10-6). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10-6). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. Conclusions: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.
KW - Genome-wide association studies
KW - Outcomes
KW - Parkinson's disease
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U2 - 10.1016/j.parkreldis.2012.04.025
DO - 10.1016/j.parkreldis.2012.04.025
M3 - Article
C2 - 22658654
AN - SCOPUS:84865312376
SN - 1353-8020
VL - 18
SP - 881
EP - 886
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 7
ER -