Common mineral nutrients in ankylosing spondylitis: A 2-sample Mendelian randomization study

Area of Science:

• Genetics and Human Health
• Nutritional Epidemiology
• Rheumatology

Background:

• Ankylosing spondylitis (AS) is a chronic inflammatory disease with complex etiology.
• The role of common mineral nutrients in AS pathogenesis remains largely uninvestigated.
• Understanding nutrient associations can inform preventative and therapeutic strategies for AS.

Purpose of the Study:

• To investigate the potential causal relationship between serum levels of calcium, zinc, copper, and selenium and the risk of developing ankylosing spondylitis (AS).
• To utilize Mendelian randomization (MR) to assess these associations, minimizing confounding factors inherent in observational studies.

Main Methods:

• A 2-sample Mendelian randomization (MR) study design was employed.
• Single nucleotide polymorphisms (SNPs) associated with calcium, zinc, copper, and selenium levels served as instrumental variables.
• Inverse-variance weighted (IVW), MR-Egger, and other methods were used to evaluate causal effects, with stringent criteria for SNP selection and pleiotropy assessment.

Main Results:

• No statistically significant causal association was found between calcium, copper, or selenium levels and AS risk using the IVW method.
• While initial IVW and Weighted Median analyses suggested a potential link between higher zinc levels and AS risk, this was not supported by MR-Egger or other sensitivity analyses.
• Tests for horizontal pleiotropy confirmed the robustness of the findings, indicating no significant pleiotropic effects of the selected SNPs.

Conclusions:

• This MR study provides no convincing evidence for a causal role of common mineral nutrients (calcium, zinc, copper, selenium) in the development of ankylosing spondylitis.
• The suggestive association observed for zinc was not robust across all analytical methods, warranting caution in interpretation.
• Further research may be necessary to elucidate the complex interplay between micronutrients and AS pathogenesis.