Functional variants in the <i>LRRK2</i> gene confer shared effects on risk for Crohn's disease and Parkinson's disease.

ABSTRACT: Crohn's disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10^-10) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10^-8). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD path

SUBMITTER: Hui KY 

PROVIDER: S-EPMC6028002 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature