Vitamin D deficiency and C-reactive protein: a bidirectional Mendelian randomization study

Area of Science:

• Nutritional biochemistry
• Genetic epidemiology
• Inflammation research

Background:

• Low vitamin D status is frequently linked to systemic low-grade inflammation, evidenced by elevated C-reactive protein (CRP) levels.
• The causal relationship and directionality between vitamin D status and CRP require clarification.

Purpose of the Study:

• To investigate the causal relationship between vitamin D status and C-reactive protein (CRP) levels.
• To determine the direction of association using Mendelian randomization (MR) analyses.

Main Methods:

• Utilized linear and non-linear Mendelian randomization (MR) analyses.
• Employed data from 294,970 White-British participants in the UK Biobank.
• Instrumented serum 25-hydroxyvitamin D [25(OH)D] and CRP using 35 and 46 genome-wide significant variants, respectively.

Main Results:

• Non-linear MR revealed an L-shaped association: CRP decreased sharply with increasing 25(OH)D in deficiency (<25 nmol/L) and plateaued around 50 nmol/L (Pnon-linear=1.49E-4).
• Pleiotropy-robust methods confirmed an inverse association between 25(OH)D and CRP in the deficiency range (P=1.10E-05), but not at higher concentrations.
• No evidence supported a causal effect of CRP on 25(OH)D in either linear or non-linear MR analyses (Plinear=0.32, Pnon-linear=0.76).

Conclusions:

• The association between 25(OH)D and CRP is likely driven by vitamin D deficiency.
• Correcting low vitamin D status presents a potential strategy for reducing chronic inflammation.