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Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
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2013 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 6, 1708.e7-1708.e13 p.Article in journal (Refereed) Published
Abstract [en]

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. (C) 2013 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
2013. Vol. 34, no 6, 1708.e7-1708.e13 p.
Keyword [en]
Parkinson's disease, GWAS, Genetic association study, Single-nucleotide polymorphism
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URN: urn:nbn:se:umu:diva-71065DOI: 10.1016/j.neurobiolaging.2012.10.019ISI: 000317417100022OAI: diva2:630112
Available from: 2013-06-18 Created: 2013-05-20 Last updated: 2014-05-07Bibliographically approved

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Axelsson, GunnarForsgren, LarsLinder, JanÖhman, Eilert
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MedicineDepartment of Pharmacology and Clinical NeuroscienceClinical Neuroscience
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