Investigating the Causal Association Between Polymyalgia Rheumatica and Hypothyroidism Using Mendelian Randomization...

Area of Science:

• Genetics
• Epidemiology
• Rheumatology

Background:

• Polymyalgia rheumatica (PMR) and hypothyroidism are common conditions with overlapping symptoms.
• The causal relationship between PMR and hypothyroidism remains unclear.

Purpose of the Study:

• To investigate the potential causal relationship between polymyalgia rheumatica (PMR) and hypothyroidism using a two-sample Mendelian randomization (MR) analysis.

Main Methods:

• Utilized genome-wide association study (GWAS) data for PMR and hypothyroidism.
• Employed the inverse variance weighted (IVW) method as the primary analysis, supplemented by weighted median, MR-Egger, simple mode, and weighted mode methods.
• Conducted sensitivity analyses using MR-PRESSO and Cochran's Q test to assess heterogeneity and pleiotropy, and performed reverse MR analysis to check for reverse causality.

Main Results:

• Mendelian randomization analysis revealed a significant causal effect of PMR on the risk of hypothyroidism (OR=1.373, P=5.84×10⁻²²).
• Reverse MR analysis also indicated a significant causal association from hypothyroidism to PMR (OR=1.195, P=9.35×10⁻¹²).
• Sensitivity analyses indicated evidence of heterogeneity but no significant horizontal pleiotropy.

Conclusions:

• A bidirectional causal relationship exists between polymyalgia rheumatica and hypothyroidism.
• Hypothyroidism may exacerbate PMR symptoms, potentially leading to misdiagnosis or overtreatment.
• The findings suggest that both conditions influence each other's development and progression.