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Authors
Nalls, Mike ASaad, Mohamad
Noyce, Alastair J
Keller, Margaux F
Schrag, Anette
Bestwick, Jonathan P
Traynor, Bryan J
Gibbs, J Raphael
Hernandez, Dena G
Cookson, Mark R
Morris, Huw R
Williams, Nigel
Gasser, Thomas
Heutink, Peter
Wood, Nick
Hardy, John
Martinez, Maria
Singleton, Andrew B
Issue Date
2014-02-01
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Hum. Mol. Genet. 2014, 23 (3):831-41Abstract
Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain.Description
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Additional Links
http://dx.doi.org/ 10.1093/hmg/ddt465http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888265/
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Archived with thanks to Human molecular geneticsae974a485f413a2113503eed53cd6c53
10.1093/hmg/ddt465
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