Genomic determinants of motor and cognitive outcomes in Parkinsons disease
Parkinsonism & Related Disorders, 08/21/2012
Chung SJ et al. – The study suggests that common variants in several genes may be associated with motor and cognitive outcomes in Parkinson’s disease (PD), with biological plausibility.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).
- 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.