Abstract Details

Title Genetic Overlap between Parkinson's Disease and Inflammatory Bowel Disease

Topic Movement Disorders

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 5-005

Background PD and IBD have been associated, implying shared pathophysiology. Characterizing genetic pleiotropy between the two conditions will improve our understanding of shared etiology and might contribute to novel drug development for both diseases.

Objective To estimate the genetic correlation between Parkinson’s disease (PD) and inflammatory bowel disease (IBD) and to identify specific loci influencing both conditions.

Design/Methods Leveraging summary statistics of genome-wide association studies on PD (N_case/control=37,688/981,372) and IBD (N_case/control=25,042/34,915), we estimated the genetic correlation between PD and each IBD subtype (Crohn’s disease (CD) and ulcerative colitis (UC)) using high definition likelihood, and identified genetic variants that jointly associate with both phenotypes via conditional false discovery rate (FDR) framework. To infer biological mechanisms underlying the detected pleiotropy, we performed bioinformatic analysis with FUMA online tools.

Results Weak but statistically significant genetic correlations were detected for PD with both CD and UC. A total of 1312 single nucleotide polymorphisms (SNPs) in 27 genomic loci and 1919 SNPs in 22 loci were identified as jointly associated with PD-CD and PD-UC, respectively, at conjunctional FDR under 0.01. For both trait pairs, the pleiotropic loci were mostly novel and comprised loci with either same or opposing genetic effects on the two phenotypes. Positional and eQTL mapping prioritized 286 PD-CD and 303 PD-UC genes, among which only <10% were differentially expressed in both colon and substantia nigra. The KEGG pathways over-represented by all prioritized genes were highly concordant between PD-CD and PD-UC, with majority being related to immune and/or autoimmune dysfunction.

Conclusions Our findings support a modest genetic link between PD and IBD, underpinned by many shared loci. The identified genetic overlap is complex, indicating the presence of both common etiology and antagonistic pleiotropy. The pathway analysis results highlighted the central role of host immunity and/or autoimmunity in the PD-IBD relationship.

Authors/Disclosures
Xiaoying Kang (Dept. Medical Epidemiology and Biostatistics, Karolinska Institutet) PRESENTER	Miss Kang has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Karin Wirdefeldt, MD (Karolinska University Hospital)	The institution of Dr. Wirdefeldt has received research support from The Parkinson Foundation in Sweden. The institution of Dr. Wirdefeldt has received research support from Swedish Research Council.