Causal relationships between rheumatism and dyslipidemia: A two-sample Mendelian randomization study

Area of Science:

• Genetics
• Rheumatology
• Metabolic Disorders

Background:

• Dyslipidemia is frequently observed in rheumatic diseases like ankylosing spondylitis (AS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE).
• The causal relationship between rheumatic diseases and dyslipidemia requires further investigation.

Purpose of the Study:

• To investigate the potential causal effects of AS, RA, and SLE on lipid profiles.
• To elucidate the genetic underpinnings of dyslipidemia in the context of rheumatic diseases.

Main Methods:

• Mendelian randomization (MR) analysis utilizing genome-wide association study (GWAS) data.
• Selection of significant and independent single-nucleotide polymorphisms as instrumental variables.
• Application of inverse variance weighted, weighted median, and MR-Egger regression methods, followed by sensitivity analyses.

Main Results:

• Ankylosing spondylitis (AS) showed positive causal effects on total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
• Systemic lupus erythematosus (SLE) demonstrated negative causal effects on TC, LDL, and HDL.
• Rheumatoid arthritis (RA) did not exhibit a significant causal effect on TC, LDL, or HDL.

Conclusions:

• AS has a causal impact on increasing TC, LDL, and HDL levels.
• SLE has a causal impact on decreasing TC, LDL, and HDL levels.
• Findings contribute to understanding the pathogenesis and treatment strategies for dyslipidemia in rheumatic disease patients.