Category: Parkinson's Disease: Genetics
Objective: The present study investigates shared genetic etiology between inflammatory bowel disease (IBD) and Parkinson’s disease (PD) using correlation and causality-based approaches.
Background: The role of intestinal inflammation in influencing Parkinson’s disease (PD) pathophysiology has become increasingly evident in recent years, with several epidemiological studies showing a strong association between IBD and PD. Genetic studies have also recently shown the existence of shared loci and genome-wide pleiotropy between Crohn’s disease (CD), a predominant subtype of IBD, and PD indicating a genetic overlap between IBD and PD. However, the directionality of interaction between IBD and PD remains unknown.
Method: We used large scale genome-wide association study summary-data (International IBD genetics consortium: 12,882 IBD cases, 21,770 controls and IPDGC consortium: 26,421 PD cases and 442,271 controls) and individual-data (In-house German IBD dataset: 3,506 cases, 4,281 controls and COURAGE-PD consortium:10,857 PD cases, 8,974 controls)
to evaluate the genetic relationship between PD, and IBD overall, and ulcerative colitis (UC), and CD independently. We used linkage disequilibrium score regression (LDSC) and polygenic risk score (PRS) to assess correlation and bidirectional Mendelian randomization (MR) to assess causality between PD and IBD. For each dataset, several best-fitting PRS were constructed using genome-wide variants, genome-wide significant variants, and variants from previously reported overlapping loci (LRKK2, GAK, MAPT, HLA-DRB5).
Results: We observed a suggestive correlation between PD and UC using the LDSC approach (rg=0.1424 (SE=0.0724); unadjusted P=0.049). Best-fit PRS using genome-wide IBD summary statistics (or genome-wide PD summary statistics) failed to demonstrate an increased risk for IBD in PD (or PD in IBD). However, IBD-PRS constructed from candidate genes LRKK2, MAPT, and HLA-DRB2 showed independent associations with a predisposition to PD after adjusting for covariates (Full-model R2 ranging from 0.0247 to 0.0273).
We failed to detect causal associations between PD and IBD or its subtypes.
Conclusion: We provide the first evidence that PRS derived from shared loci between PD and IBD could play an important role in predicting PD.
To cite this abstract in AMA style:
S. Grover, E. Wacker, A. Kumar-Sreelatha, A. Elbaz, R. Krüger, T. Gasser, D. Ellinghaus, M. Sharma. Genetic correlation and potential causal relationship between inflammatory bowel disease and Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/genetic-correlation-and-potential-causal-relationship-between-inflammatory-bowel-disease-and-parkinsons-disease/. Accessed September 7, 2024.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-correlation-and-potential-causal-relationship-between-inflammatory-bowel-disease-and-parkinsons-disease/