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dc.contributor.authorNalls, Mike A
dc.contributor.authorSaad, Mohamad
dc.contributor.authorNoyce, Alastair J
dc.contributor.authorKeller, Margaux F
dc.contributor.authorSchrag, Anette
dc.contributor.authorBestwick, Jonathan P
dc.contributor.authorTraynor, Bryan J
dc.contributor.authorGibbs, J Raphael
dc.contributor.authorHernandez, Dena G
dc.contributor.authorCookson, Mark R
dc.contributor.authorMorris, Huw R
dc.contributor.authorWilliams, Nigel
dc.contributor.authorGasser, Thomas
dc.contributor.authorHeutink, Peter
dc.contributor.authorWood, Nick
dc.contributor.authorHardy, John
dc.contributor.authorMartinez, Maria
dc.contributor.authorSingleton, Andrew B
dc.date.accessioned2015-05-07T15:36:33Zen
dc.date.available2015-05-07T15:36:33Zen
dc.date.issued2014-02-01en
dc.date.submitted2015en
dc.identifier.citationHum. Mol. Genet. 2014, 23 (3):831-41en
dc.identifier.issn1460-2083en
dc.identifier.pmid24057672en
dc.identifier.doi10.1093/hmg/ddt465en
dc.identifier.urihttp://hdl.handle.net/2336/552462en
dc.descriptionTo 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.en
dc.description.abstractParkinson'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.
dc.language.isoenen
dc.publisherOxford Univ Pressen
dc.relation.urlhttp://dx.doi.org/ 10.1093/hmg/ddt465en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888265/en
dc.rightsArchived with thanks to Human molecular geneticsen
dc.subjectParkinsonsveikien
dc.subjectCrohns-sjúkdómuren
dc.subjectGeðklofien
dc.subjectArfgengien
dc.subject.meshComorbidityen
dc.subject.meshCpG Islandsen
dc.subject.meshCrohn Diseaseen
dc.subject.meshDNA Methylationen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshHumansen
dc.subject.meshParkinson Diseaseen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshRisk Factorsen
dc.subject.meshSchizophreniaen
dc.titleGenetic comorbidities in Parkinson's disease.en
dc.typeArticleen
dc.contributor.department[ 1 ] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA [ 2 ] Ctr Physiopathol Toulouse Purpan, Inst Natl Sante & Rech Med, UMR 1043, Toulouse, France [ 3 ] Univ Toulouse 3, F-31062 Toulouse, France [ 4 ] UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, London, England [ 5 ] UCL Inst Neurol, Dept Clin Neurosci, London, England [ 6 ] Temple Univ, Dept Biol Anthropol, Philadelphia, PA 19122 USA [ 7 ] Queen Mary Univ London, Wolfson Inst Prevent Med, Barts & London Sch Med & Dent, London, England [ 8 ] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Sch Med, Cardiff CF10 3AX, S Glam, Wales [ 9 ] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany [ 10 ] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany [ 11 ] UCL, Inst Neurol, Dept Mol Neurosci, London, England [ 12 ] UCL, UCL Genet Inst, London, Englanden
dc.identifier.journalHuman molecular geneticsen
dc.rights.accessOpen Accessen
refterms.dateFOA2018-09-12T15:11:28Z
html.description.abstractParkinson'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.


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