Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Genetic comorbidities in Parkinson's disease.
Hum. Mol. Genet. 23, 831-841 (2014)
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
Zeitschrift
Human Molecular Genetics
Quellenangaben
Band: 23,
Heft: 3,
Seiten: 831-841
Verlag
Oxford University Press
Verlagsort
Oxford
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Human Genetics (IHG)