Causal relationships between Sjögren's syndrome and Parkinson's disease: A Mendelian randomization study

Int J Rheum Dis. 2024 Mar;27(3):e15128. doi: 10.1111/1756-185X.15128.

Abstract

Background: Epidemiological and observational studies have indicated an association between Sjögren's syndrome (SS) and Parkinson's disease (PD). However, consistent conclusions have not been reached due to various limitations. In order to determine whether SS and PD are causally related, we conducted a Mendelian randomization study (MR) with two samples.

Methods: Data for SS derived from the FinnGen consortium's R9 release (2495 cases and 365 533 controls). Moreover, data for PD were acquired from the publicly available GWAS of European ancestry, which involved 33 674 cases and 449 056 controls. The inverse variance weighted, along with four other effective methodologies, were employed to comprehensively infer the causal relationships between SS and PD. To assess the estimation's robustness, a number of sensitivity studies were performed. To determine the probability of reverse causality, we performed a reverse MR analysis.

Results: There was no evidence of a significant causal effect of SS on PD risks based on the MR [odds ratio (OR) = 1.03; 95% confidence interval (CI) = 0.95-1.11; p = .45]. Similarly, no evidence supported the causal effects of PD on SS (OR = 0.92; 95% CI = 0.81-1.04; p = .20). These findings held up under rigorous sensitivity analysis.

Conclusions: MR bidirectional analysis did not reveal any cause-and-effect relationship between SS and PD, or vice versa. Further study of the mechanisms that may underlie the probable causal association between SS and PD is needed.

Keywords: Parkinson's disease; Sjögren's syndrome; mendelian randomization; single nucleotide polymorphisms.

MeSH terms

  • Causality
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Odds Ratio
  • Parkinson Disease* / diagnosis
  • Parkinson Disease* / epidemiology
  • Parkinson Disease* / genetics
  • Sjogren's Syndrome* / diagnosis
  • Sjogren's Syndrome* / epidemiology
  • Sjogren's Syndrome* / genetics