The Relationship Between Systemic Lupus Erythematosus and Osteoporosis Based on Different Ethnic Groups: a Two-Sample...

Area of Science:

• Genetics
• Rheumatology
• Epidemiology

Background:

• Observational studies on systemic lupus erythematosus (SLE) and osteoporosis (OP) are limited by confounding variables and reverse causality.
• Establishing a causal link between SLE and OP is crucial for understanding disease mechanisms and developing targeted therapies.

Purpose of the Study:

• To investigate the potential causal relationship between SLE and OP in East Asian and European populations using Mendelian randomization (MR).
• To assess bidirectional causality and evaluate potential confounding factors and pleiotropy.

Main Methods:

• Two-sample Mendelian randomization analysis utilizing publicly available genome-wide association study data for SLE, OP, bone mineral density (BMD), and OP with fracture.
• Employing inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods for primary analysis.
• Conducting sensitivity analyses including MR-PRESSO, MR-Egger intercept, Cochran's Q test, and leave-one-out analysis to assess heterogeneity, pleiotropy, and stability. Reverse MR analysis was performed to check for reverse causality.

Main Results:

• A significant positive causal relationship was found between genetically predicted SLE and OP in the East Asian population (IVW OR=1.05, 95% CI=1.01-1.09, P=0.009).
• No significant heterogeneity or horizontal pleiotropy was detected in the East Asian cohort.
• No significant genetically predicted causal relationship between SLE and OP was observed in the European population. Reverse MR analysis indicated no reverse causality.

Conclusions:

• Genetically predicted SLE demonstrates a positive causal effect on OP in the East Asian population.
• The observed association between SLE and OP in European populations may be influenced by confounding variables, as no causal link was established.
• This MR study provides robust evidence for a causal relationship between SLE and OP in East Asians, distinct from European populations.