Illustration showing the gut and the brain to symbolize the gut-brain connection or gut brain axis, which has been implicated in Parkinson's disease and inflammatory bowel disease
Credit: ChrisChrisW/Getty Images

Research led by the Icahn School of Medicine at Mount Sinai, New York, has confirmed a link between the genetics of inflammatory bowel disease (IBD) and Parkinson’s disease.

The team that discovered the connection hopes their findings can help design therapies that could target both conditions.

“Our research not only links these two diseases genetically but also sets the stage for new forms of treatment, and potentially prevention strategies, that could lessen the burden of these diseases on patients,” said first author of the Genome Medicine paper describing the research, Meltem Ece Kars, a postdoctoral researcher at The Charles Bronfman Institute for Personalized Medicine, in a press statement.

People with autoimmune inflammatory bowel disease, either Crohn’s disease or ulcerative colitis, appear to be at increased risk for Parkinson’s compared with the general population. It has recently been suggested that this may be linked to the “gut-brain axis” hypothesis, with chronic inflammation of the gut leading to neurodegeneration.

Genetic variants in the leucine-rich repeat kinase 2 gene (LRRK2) are common in Parkinson’s disease patients and some earlier studies have also found mutations in this gene in people with Crohn’s disease.

In the current study, the researchers looked for common genetic links between the two conditions. They looked at genomic sequence (exome data) from 67 patients with both IBD and Parkinson’s disease selected from the BioMe BioBank and the UK Biobank. In particular, they searched for missense variants in LRRK2, but also looked for other genetic associations. They used several methods including the network-based heterogeneity clustering approach, which is designed for analysis of small group genetic data.

Overall, several variants in LRRK2 were linked to both IBD and Parkinson’s disease including the G2019S and N2081D variants, which were identified as linking IBD and Parkinson’s in previous studies. The two most significant genes linked to both conditions appeared to be LRRK2 and IL10RA (Interleukin-10 receptor subunit alpha gene), although the team identified six gene clusters relevant to both conditions.

The genetic pathways identified by the researchers had links to immunity, inflammation and autophagy, the cellular recycling system.

“Our study highlights the significance of shared genetic factors in the IBD-Parkinson’s disease overlap by both supporting previous findings and introducing novel candidate genes and variants,” wrote the authors.

“Future investigation of the interplay between inflammation and autophagy could in principle provide a better understanding of the shared etiology of IBD and Parkinson’s disease and potential therapeutic targets for drug development and repurposing.”

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