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dc.contributor.authorLatourelle, Jeanne C.en_US
dc.contributor.authorPankratz, Nathanen_US
dc.contributor.authorDumitriu, Alexandraen_US
dc.contributor.authorWilk, Jemma B.en_US
dc.contributor.authorGoldwurm, Stefanoen_US
dc.contributor.authorPezzoli, Giannien_US
dc.contributor.authorMariani, Claudio B.en_US
dc.contributor.authorDeStefano, Anita L.en_US
dc.contributor.authorHalter, Cherylen_US
dc.contributor.authorGusella, James F.en_US
dc.contributor.authorNichols, William C.en_US
dc.contributor.authorMyers, Richard H.en_US
dc.contributor.authorForoud, Tatianaen_US
dc.date.accessioned2011-12-29T21:02:15Z
dc.date.available2011-12-29T21:02:15Z
dc.date.copyright2009
dc.date.issued2009-9-22
dc.identifier.citationLatourelle, Jeanne C, Nathan Pankratz, Alexandra Dumitriu, Jemma B Wilk, Stefano Goldwurm, Gianni Pezzoli, Claudio B Mariani, Anita L DeStefano, Cheryl Halter, James F Gusella, William C Nichols, Richard H Myers, Tatiana Foroud. "Genomewide association study for onset age in Parkinson disease." BMC Medical Genetics 10:98. (2009)
dc.identifier.issn1471-2350
dc.identifier.urihttps://hdl.handle.net/2144/2496
dc.description.abstractBACKGROUND: Age at onset in Parkinson disease (PD) is a highly heritable quantitative trait for which a significant genetic influence is supported by multiple segregation analyses. Because genes associated with onset age may represent invaluable therapeutic targets to delay the disease, we sought to identify such genetic modifiers using a genomewide association study in familial PD. There have been previous genomewide association studies (GWAS) to identify genes influencing PD susceptibility, but this is the first to identify genes contributing to the variation in onset age. METHODS: Initial analyses were performed using genotypes generated with the Illumina HumanCNV370Duo array in a sample of 857 unrelated, familial PD cases. Subsequently, a meta-analysis of imputed SNPs was performed combining the familial PD data with that from a previous GWAS of 440 idiopathic PD cases. The SNPs from the meta-analysis with the lowest p-values and consistency in the direction of effect for onset age were then genotyped in a replication sample of 747 idiopathic PD cases from the Parkinson Institute Biobank of Milan, Italy. RESULTS: Meta-analysis across the three studies detected consistent association (p < 1 × 10-5) with five SNPs, none of which reached genomewide significance. On chromosome 11, the SNP with the lowest p-value (rs10767971; p = 5.4 × 10-7) lies between the genes QSER1 and PRRG4. Near the PARK3 linkage region on chromosome 2p13, association was observed with a SNP (rs7577851; p = 8.7 × 10-6) which lies in an intron of the AAK1 gene. This gene is closely related to GAK, identified as a possible PD susceptibility gene in the GWAS of the familial PD cases. CONCLUSION: Taken together, these results suggest an influence of genes involved in endocytosis and lysosomal sorting in PD pathogenesis.en_US
dc.description.sponsorshipNational Institutes of Health (R01 NS37167, RO1 NS036711); Robert P. and Judith N. Goldberg Foundation; Bumpus Foundation; Harvard NeuroDiscovery Centeren_US
dc.language.isoen
dc.publisherBioMed Centralen_US
dc.rightsCopyright 2009 Latourelle et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.titleGenomewide Association Study for Onset Age in Parkinson Diseaseen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/1471-2350-10-98
dc.identifier.pmid19772629
dc.identifier.pmcid2758866


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Copyright 2009 Latourelle et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as Copyright 2009 Latourelle et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.