Genomic determinants of motor and cognitive outcomes in Parkinson's disease.
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.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Sun Ju
SJ
Chung
Sebastian M
SM
Armasu
Joanna M
JM
Biernacka
Kari J
KJ
Anderson
Timothy G
TG
Lesnick
David N
DN
Rider
Julie M
JM
Cunningham
J
J
Eric Ahlskog
Roberta
R
Frigerio
Demetrius M
DM
Maraganore
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009043:Motor Activity / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C579285:CLRN3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C418741:TCIM protein, human