title: Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease.
abstract: Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway. lasse.pihlstrom@ous-hf.no
authors.forename: Lasse
authors.initials: L
authors.lastname: Pihlstrøm
authors.forename: Gunnar
authors.initials: G
authors.lastname: Axelsson
authors.forename: Kari Anne
authors.initials: KA
authors.lastname: Bjørnarå
authors.forename: Nil
authors.initials: N
authors.lastname: Dizdar
authors.forename: Camilla
authors.initials: C
authors.lastname: Fardell
authors.forename: Lars
authors.initials: L
authors.lastname: Forsgren
authors.forename: Björn
authors.initials: B
authors.lastname: Holmberg
authors.forename: Jan Petter
authors.initials: JP
authors.lastname: Larsen
authors.forename: Jan
authors.initials: J
authors.lastname: Linder
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.forename: Ole-Bjørn
authors.initials: OB
authors.lastname: Tysnes
authors.forename: Eilert
authors.initials: E
authors.lastname: Ohman
authors.forename: Espen
authors.initials: E
authors.lastname: Dietrichs
authors.forename: Mathias
authors.initials: M
authors.lastname: Toft
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D010300:Parkinson Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013548:Sweden / Q000453:epidemiology