"In this study lead by Professor Nalls we looked at genetic information from a large number of people with Parkinson's and a large number without. We gathered information from genetic regions associated with factors/diseases that have been previously reported to be associated with Parkinson's. We then compared the two groups to see if there were differences in these regions. We found that the Crohn's disease, which is a type of inflammatory bowel disease, and schizophrenia genetic profiles were statistically associated Parkinson's. This potentially gives us further insight into the mechanisms underlying such diseases."
"For those that follow the PREDICT-PD study you will see that the method above is the inverse of what we are doing in PREDICT. Here we are using genetic data to identify genetic risk of associated diseases in those with established PD, whereas in PREDICT we are using the associated diseases and factors to identify risk of PD (and PD genes)."
- Alastair Noyce
Hum Mol Genet. 2013 Sep 20. [Epub ahead of print]
Nalls MA, Saad M, Noyce AJ, Keller MF, Schrag A, Bestwick JP, Traynor BJ, Gibbs JR, Hernandez DG, Cookson MR, Morris HR, Williams N, Gasser T, Heutink P, Wood N, Hardy J, Martinez M, Singleton AB; for the International Parkinson's Disease Genomics Consortium (IPDGC); The Wellcome Trust Case Control Consortium 2 (WTCCC2); North American Brain Expression Consortium (NABEC); the United Kingdom Brain Expression Consortium (UKBEC).
Source
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
Abstract
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 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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