High-Resolution Whole-Genome Association Study Of Parkinson Disease
Demetrius M. Maraganore (1), Mariza de Andrade (2), Timothy G. Lesnick (2), Kari J. Strain (2), Matthew J. Farrer (3), Walter A. Rocca (1,2), P. V. Krishna Pant (4), Kelly A. Frazer (4), David R. Cox (4), and Dennis G. Ballinger (4)
Departments of (1) Neurology and (2) Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN; (3) Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL; and (4) Perlegen Sciences, Mountain View, CA
The authors performed a two-tiered, whole-genome association study of Parkinson disease (PD). For tier 1, they individually genotyped 198,345 uniformly spaced and informative single-nucleotide polymorphisms (SNPs) in 443 sibling pairs discordant for PD. For tier 2a, they individually genotyped 1,793 PD-associated SNPs and 300 genomic control SNPs in 332 matched case unrelated control pairs.
They identified 11 SNPs that were associated with PD in both tier 1 and tier 2 samples and had the same direction of effectIn analysis of the combined tier 1 and tier 2b data, the two SNPs with the lowest P values tagged the PARK10 late-onset PD susceptibility locus.
Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility.
Abstract available online.
(C) American Journal of Human Genetics.
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