Association Between Serum Galectin‐3 and Parkinson's Disease: A Two‐Sample Mendelian Randomization Study

• Published in: Brain and behavior 2024-10, Vol.14 (10), p.e70103-n/a
• Main Authors: Pan, Rui, Li, Wei, Wang, Jinyuan, Xie, Jiarong, Weng, Xiucan, Yang, Ying, Shi, Xiaolei
• Format: Article
• Language: English
• Subjects: Biomarkers - blood; Blood Proteins - analysis; Blood Proteins - genetics; Confounding (Statistics); Disease; Galectin 3 - blood; Galectin 3 - genetics; Galectins - blood; Galectins - genetics; galectin‐3; genetic instrument; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Humans; Mendelian randomization; Mendelian Randomization Analysis; Original; Parkinson Disease - blood; Parkinson Disease - genetics; Parkinson's disease; Polymorphism, Single Nucleotide; Statistics
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.70103

ABSTRACT Background Parkinson's disease (PD) is a prevalent neurodegenerative disorder with poor prognosis. Observational studies have demonstrated a significant correlation between serum galectin‐3 and PD, suggesting a potential role of galectin‐3 as a biomarker for PD. However, it is still unclear whether galectin‐3 contributes to the risk of the disease. Methods A two‐sample Mendelian randomization (MR) approach was used in this study. Genetic instruments for serum galectin‐3 level were selected from a genome‐wide association study (GWAS), including 30,931 European individuals. Summary‐level statistics for PD were derived from another published GWAS, including 33,674 cases and 449,056 controls. Primary analysis was conducted using the inverse‐variance weighting (IVW) method. Weighted median, MR‐Egger, simple mode, weighted mode, and MR‐pleiotropy residual sum and outlier (MR‐PRESSO) methods were used as complementary analyses. To detect heterogeneity, Cochran's Q statistic and leave‐one‐out analysis were used. For testing potential horizontal pleiotropy, the MR‐Egger intercept test and MR‐PRESSO global test were conducted. Results MR analysis using IVW model (OR 1.112, 95% CI 1.025–1.206, p = 0.010), weighted median (OR 1.135, 95% CI 1.037–1.242, p = 0.006), weighted mode (OR 1.142, 95% CI 1.038–1.257, p = 0.030), and MR‐PRESSO (OR 1.112, 95% CI 1.046–1.182, p = 0.012) presented a consistent result, indicating that increased serum galectin‐3 was associated with a higher risk of PD. No heterogeneity or horizontal pleiotropy was detected in the analyses. Conclusions The study shows a suggestive association between galectin‐3 and PD. Increasing serum galectin‐3 was associated with an increase in PD risk. Galectin‐3 may play an important role in the causal pathway to PD. A suggestive association between genetic susceptibility to serum galectin‐3 and risk of Parkinson's disease (PD) was demonstrated. Galectin‐3 may play an important role in the causal pathway to PD.