Association between inflammatory bowel disease and Parkinson’s disease: A Mendelian randomization study

Freuer, Dennis; Meisinger, Christa

doi:10.1038/s41531-022-00318-7

Cited by 18 publications

(27 citation statements)

References 25 publications

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“…It has also been demonstrated that IBD and PD share common genetic risk profiles, such as CARD15 , LRRK2 , HLA , and MAPT genes ( 71 , 72 ). Notably, a two-sample Mendelian randomization study on IBD and PD genetically predicted that neither IBD nor its subtypes CD and UC were associated with an increased risk of PD ( 73 ), although another Mendelian randomization study confirmed a causal relationship between PD and IBD ( 74 ).…”

Section: Discussionmentioning

confidence: 99%

The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis

Wan

et al. 2023

Front. Immunol.

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Parkinson’s disease (PD) is a neurodegenerative disorder that frequently occurs in the older population. Previous epidemiological studies have suggested an association between PD and autoimmune diseases (AIDs). However, some studies have shown conflicting results. This study aimed to summarize existing epidemiological studies on the association between PD with AIDs and to conduct a meta-analysis of combinable results. Four electronic databases (PubMed, Embase, Web of Science Core Collection, and MEDLINE) were searched from each database’s inception date until December 12, 2022. All studies that explored the relationship between PD and AIDs were included for quantitative analysis and qualitative review. The pooled relative risk with 95% confidence intervals (CIs) was calculated using a random or fixed effects model. A total of 46 observational studies involving 873,643 patients and 13,402,821 controls were included; ultimately, 38 studies were included in the meta-analysis. The risk of PD combined with AIDs was significantly higher (odds ratio [OR]=1.55, 95% CI: 1.33–1.81), and subgroup analysis found no significant differences in risk by study type, gender, age, and race. Regarding the AID types, the results showed an increased risk of PD combined with bullous pemphigoid (OR=2.67, 95% CI: 2.15–3.31), inflammatory bowel disease (OR=1.30, 95% CI: 1.18–1.45), Crohn’s disease (OR=1.30, 95% CI: 1.20–1.42), ulcerative colitis (OR=1.31, 95% CI: 1.14–1.50), Sjögren’s syndrome (OR=1.61, 95% CI: 1.24–2.09), and Graves’ disease (OR=1.45, 95% CI: 1.24–1.70) than controls. However, there appeared to be no significant association between PD and systemic lupus erythematosus (OR=0.82, 95% CI: 0.66–1.03), multiple sclerosis (OR=2.02, 95% CI: 0.87–4.70), rheumatoid arthritis (OR=0.79, 95% CI: 0.61–1.03), or celiac disease (OR=1.16, 95% CI: 0.79–1.69). This study supports the existence of a strong link between AIDs and PD. When PD and AIDs are identified, clinicians need to be aware of the possibility of coexistence. However, there are some limitations of this study, such as the apparent heterogeneity of some of the results and the fact that most of the included study types were retrospective. Therefore, future larger prospective cohort studies are needed to further explore the interaction between PD and AIDs.Systematic review registrationINPLASY, identifier INPLASY202280088.

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Section: Discussionmentioning

confidence: 99%

The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis

Wan

et al. 2023

Front. Immunol.

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“…Freuer et al. conducted an MR study of the association between IBD and PD and reported that genetically predicted IBD was not associated with an increased risk of PD ( 12 ). Unfortunately, their analysis was unidirectional, which means that the question of whether PD can increase the risk of IBD remains unanswered.…”

Section: Introductionmentioning

confidence: 99%

Are neurodegenerative diseases associated with an increased risk of inflammatory bowel disease? A two-sample Mendelian randomization study

Cui

et al. 2022

Front. Immunol.

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BackgroundSeveral studies have shown that neurodegenerative diseases (e.g., Parkinson’s disease [PD] and Alzheimer’s disease [AD]) are associated with inflammatory bowel disease (IBD), but the causality and direction of their associations remain unclear. Mendelian randomization (MR) studies have explored the causal effects of IBD on PD and AD. However, only a few studies examined this reverse association. Thus, this study aimed to explore whether there are causal associations of genetically predicted PD and AD with IBD, using a two-sample MR study.MethodsSummary statistics for IBD, ulcerative colitis (UC), and Crohn’s disease (CD) were derived from a genome-wide association study (GWAS) meta-analysis, which included the International IBD Genetics Consortium and the UK IBD Genetics Consortium (n=59,957). Genetic variants associated with the largest meta-analysis of GWAS of PD (n=1,474,097) and AD (n=455,258) were used as instrumental variables. We used multiple methods, including inverse variance weighted (IVW), weighted median (WM), MR-Egger regression, weighted mode, and Robust Adjusted Profile Score (RAPS) methods, to estimate the effects of genetically predicted PD and AD on IBD. To confirm the validity of the analysis, we also evaluated the pleiotropic effects, heterogeneity, and leave-one-out sensitivity analysis that drive causal associations.ResultsThe results of the IVW method, WM, and RAPS showed that genetically predicted PD was significantly associated with an increased risk of UC (odds ratio [OR]IVW=1.068, ORWM=1.107, ORRAPS=1.069, all P<0.05). Additionally, we found that there were significant associations of genetically predicted PD with CD (ORIVW=1.064, ORRAPS=1.065, all P<0.05) and IBD (ORIVW=1.062, ORRAPS=1.063, all P<0.05) using the IVW method and RAPS. However, there was no significant causal evidence of genetically predicted AD in IBD, UC, or CD among all MR methods. In all MR analyses, there were no horizontal pleiotropy (all P>0.05), or statistical heterogeneity. The sensitivity analysis results of the leave-one-out sensitivity analysis showed that the causal effect estimations of genetically predicted PD and AD on IBD were robust.ConclusionsOur MR study corroborated a causal association between genetically predicted PD and IBD but did not support a causal effect of genetically predicted AD on IBD. More animal experiments or population-based observational studies are required to clarify the underlying mechanisms of PD and IBD.

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“…The main features of the included studies were summarized in Table 1 . Of the 14 studies included, nine were cohort studies ( 11 – 15 , 18 – 21 ), two cross-sectional studies ( 10 , 22 ), two mendelian randomization studies ( 26 , 27 ) and the remaining one was a case-control study ( 16 ). Altogether, these articles were published between 2011 and 2022, involving more than 13.4 million individuals.…”

Section: Resultsmentioning

confidence: 99%

“…Another a meta-analysis was conducted by Zhu et al ( 25 ) demonstrated that the overall risk of PD was significantly higher in IBD patients than in the general population, with the RR was 1.24 (95% CI:1.15, 1.34, and P < 0.001). In recent years, several clinical studies with large samples have been conducted to investigate the association between IBD and PD, again, with conflicting results ( 10 , 11 , 18 , 19 , 26 , 27 ). In these studies, two (cohort study) reported positive relationships ( 10 , 19 ), while three (two mendelian randomization studies and one cohort study) showed no association ( 18 , 26 , 27 ) and one (cross-sectional study) found an inverse relationship ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, several clinical studies with large samples have been conducted to investigate the association between IBD and PD, again, with conflicting results ( 10 , 11 , 18 , 19 , 26 , 27 ). In these studies, two (cohort study) reported positive relationships ( 10 , 19 ), while three (two mendelian randomization studies and one cohort study) showed no association ( 18 , 26 , 27 ) and one (cross-sectional study) found an inverse relationship ( 10 ). Currently, the effects of IBD on PD risk are still controversial.…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory bowel disease and risk of Parkinson’s disease: evidence from a meta-analysis of 14 studies involving more than 13.4 million individuals

Zhang

et al. 2023

Front. Med.

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BackgroundThe relationship between inflammatory bowel disease (IBD) and the risk of Parkinson’s Disease (PD) has been investigated in several epidemiological studies. However, the results of these studies were inconclusive and inconsistent. We evaluated the potential relationship between IBD and PD risk by a meta-analysis.MethodsSearch the electronic databases PubMed, Embase and Cochrane databases from inception to November 30, 2022, to identify relevant studies that assess the risk of PD in patients with IBD. The cohort, cross-sectional, mendelian randomization and case-control studies that reported risk estimates of PD and IBD were included in our analysis. The random-effect model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs).ResultsIn total, 14 studies (nine cohort studies, two cross-sectional studies, two mendelian randomization studies and one case-control study) involving more than 13.4 million individuals were analyzed in our analysis. Our results suggested that the risk of PD in IBD patients is moderately increased, with the pooled RR was 1.17 (95% CI: 1.03–1.33, P = 0.019). Omit of any single study from this analysis had little effect on the combined risk estimate. No evidence of publication bias was found. In the subgroup analysis, the combined RR was 1.04 (95% CI: 0.96, 1.12, P = 0.311) for Crohn’s disease (CD), and 1.18 (95% CI: 1.06, 1.31, P = 0.002) for ulcerative colitis (UC). In addition, a significant association was identified in patients with IBD aged ≥ 60 years (RR = 1.22; 95% CI: 1.06–1.41, P = 0.007), but not in age < 60 years (RR = 1.19; 95% CI: 0.58–2.41, P = 0.639). Meanwhile, the meta-analysis results suggested a protective role for IBD medication use against PD development, with the RR was 0.88 (95% CI: 0.74, 1.04, P = 0.126).ConclusionOur results indicated that patients with IBD had a moderately higher risk of PD compared to non-IBD individuals. Patients with IBD should be aware of the potential risks for PD, especially who were ≥ 60 years old.

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Association between inflammatory bowel disease and Parkinson’s disease: A Mendelian randomization study

Cited by 18 publications

References 25 publications

The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis

The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis

Are neurodegenerative diseases associated with an increased risk of inflammatory bowel disease? A two-sample Mendelian randomization study

Inflammatory bowel disease and risk of Parkinson’s disease: evidence from a meta-analysis of 14 studies involving more than 13.4 million individuals

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