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Nalls, M.A.* ; Saad, M.* ; Noyce, A.J.* ; Keller, M.F.* ; Schrag, A.* ; Bestwick, J.P.* ; Traynor, B.J.* ; Gibbs, J.R.* ; Hernandez, D.G.* ; Cookson, M.R.* ; Morris, H.R.* ; Williams, N.* ; Gasser, T.* ; Heutink, P.* ; Wood, N.* ; Hardy, J.* ; Martinez, M.* ; Singleton, A.B.* ; International Parkinson's Disease Genomics Consortium (IPDGC) (Illig, T. ; Lichtner, P.) ; Wellcome Trust Case Control Consortium 2 (WTCCC2) (*) ; North American Brain Expression Consortium (*) ; United Kingdom Brain Expression Consortium (UKBEC) (*)

Genetic comorbidities in Parkinson's disease.

Hum. Mol. Genet. 23, 831-841 (2014)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genome-wide Association; Inflammatory-bowel-disease; Psoriasis Susceptibility Loci; C-reactive Protein; Colitis-risk Loci; Mendelian Randomization; Sequence Variants; Common Variants; Identifies 3; Cardiovascular-disease
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Quellenangaben Band: 23, Heft: 3, Seiten: 831-841 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed