Causal relationship between circulating insulin-like growth factor-1 and Parkinson's disease: a two-sample Mendelian...

Area of Science:

• Neuroscience
• Genetics
• Endocrinology

Background:

• Observational studies suggest a link between insulin-like growth factor-1 (IGF-1) and Parkinson's disease (PD).
• The causal relationship between IGF-1 levels and PD risk remains unclear.
• Genetic factors influencing IGF-1 levels are investigated for their role in PD.

Purpose of the Study:

• To investigate the potential causal relationship between genetically predicted IGF-1 levels and the risk of Parkinson's disease.
• To utilize Mendelian randomization to assess the impact of IGF-1 on PD.

Main Methods:

• Genome-wide association studies (GWAS) were reviewed to identify single nucleotide polymorphisms (SNPs) associated with IGF-1 and PD.
• A two-sample Mendelian randomization (MR) analysis was performed.
• The inverse-variance weighted (IVW) method was employed as the primary analytical approach.

Main Results:

• Mendelian randomization analysis indicated a significant association between higher IGF-1 levels and an increased risk of PD (OR, 1.020; 95% CI, 1.003-1.038; p=0.0215).
• Statistical tests (MR-Egger intercept) suggested that horizontal pleiotropy was unlikely to bias the findings.
• Leave-one-out analysis confirmed the robustness of the results, with no single SNP unduly influencing the outcome.

Conclusions:

• This study provides genetic evidence suggesting that elevated IGF-1 levels may be causally associated with an increased risk of developing Parkinson's disease.
• The findings contribute to understanding the complex interplay between metabolic factors and neurodegenerative diseases.