The genetic contribution to a number of neurological disorders is thought to be complex in nature, disease risk being driven by a combination of risk alleles commonly present in the human genome. Recently the completion of stages I and II of the international Haplotype Map project and the availability of high-plex SNP assays has made genome wide assay of common genetic variability a realistic endeavor. We have applied genome wide association analysis using 500,000SNPs to a Parkinsons disease cohort from the NIH funded neurogenetics repository. We have combined the data from this work with collaborators from Germany, the US, the UK and Japan. This work has lead to the identification of common variability in SNCA and MAPT as unequivocal risk factors for Parkinson's disease. We have now extended this work and combined results with other large genotyping projects in PD and related diseases to identify additional risk loci for this disease, identifying an additional 15 risk loci for Parkinson's disease. This work showed for the first time unequivocal evidence that the genetic basis of Parkinson's disease is complex and substantive. Not only has this effort revealed a greater than previously thought genetic component, but it has also nominated a host of new targets with which to understand the biological basis of Parkinson's disease. Our current effort revolves around a mega-meta analysis of PD GWA, that is a large collaborative effort between all groups that have generated GWA data in Caucasian PD subjects. This analysis revealed approximately 30 loci, and we are currently working on replication of these in an independent series. The next component of this work involves large scale resequencing to find biologically relevant variants that mediate the common risk and in addition are responsible as rare causal mutations. We are currently preparing a manuscript for submission that reports the identification and replication of 28 independent risk loci for Parkinson's disease.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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Burciu, Roxana G; Seidler, Rachael D; Shukla, Priyank et al. (2018) Multimodal neuroimaging and behavioral assessment of ?-synuclein polymorphism rs356219 in older adults. Neurobiol Aging 66:32-39
Billingsley, K J; Bandres-Ciga, S; Saez-Atienzar, S et al. (2018) Genetic risk factors in Parkinson's disease. Cell Tissue Res 373:9-20
Blauwendraat, Cornelis; Kia, Demis A; Pihlstrøm, Lasse et al. (2018) Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease. Neurobiol Aging 64:159.e5-159.e8
Marioni, Riccardo E; McRae, Allan F; Bressler, Jan et al. (2018) Meta-analysis of epigenome-wide association studies of cognitive abilities. Mol Psychiatry 23:2133-2144
Mollenhauer, Brit; Caspell-Garcia, Chelsea J; Coffey, Christopher S et al. (2017) Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls. Neurology 89:1959-1969
Capozzo, Rosa; Sassi, Celeste; Hammer, Monia B et al. (2017) Clinical and genetic analyses of familial and sporadic frontotemporal dementia patients in Southern Italy. Alzheimers Dement 13:858-869
Noyce, Alastair J; Kia, Demis A; Hemani, Gibran et al. (2017) Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study. PLoS Med 14:e1002314
Hammer, Monia B; Ding, Jinhui; Mochel, Fanny et al. (2017) SLC25A46 Mutations Associated with Autosomal Recessive Cerebellar Ataxia in North African Families. Neurodegener Dis 17:208-212
Blauwendraat, Cornelis; Faghri, Faraz; Pihlstrom, Lasse et al. (2017) NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases. Neurobiol Aging 57:247.e9-247.e13
Larsson, Susanna C; Singleton, Andrew B; Nalls, Mike A et al. (2017) No clear support for a role for vitamin D in Parkinson's disease: A Mendelian randomization study. Mov Disord 32:1249-1252

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