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

BACKGROUND: Low vitamin D status is often associated with systemic low-grade inflammation as reflected by elevated C-reactive protein (CRP) levels. We investigated the causality and direction of the association between vitamin D status and CRP using linear and non-linear Mendelian randomization (MR)...

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Detalles Bibliográficos
Autores principales: Zhou, Ang, Hyppönen, Elina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9908047/
https://www.ncbi.nlm.nih.gov/pubmed/35579027
http://dx.doi.org/10.1093/ije/dyac087
Descripción
Sumario:BACKGROUND: Low vitamin D status is often associated with systemic low-grade inflammation as reflected by elevated C-reactive protein (CRP) levels. We investigated the causality and direction of the association between vitamin D status and CRP using linear and non-linear Mendelian randomization (MR) analyses. METHODS: MR analyses were conducted using data from 294 970 unrelated participants of White-British ancestry from the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] and CRP concentrations were instrumented using 35 and 46 genome-wide significant variants, respectively. RESULTS: In non-linear MR analysis, genetically predicted serum 25(OH)D had an L-shaped association with serum CRP, where CRP levels decreased sharply with increasing 25(OH)D concentration for participants within the deficiency range (<25 nmol/L) and levelled off at ∼50 nmol/L of 25(OH)D (P(non-linear) = 1.49E-4). Analyses using several pleiotropy-robust methods provided consistent results in stratified MR analyses, confirming the inverse association between 25(OH)D and CRP in the deficiency range (P = 1.10E-05) but not with higher concentrations. Neither linear or non-linear MR analysis supported a causal effect of serum CRP level on 25(OH)D concentration (P(linear) = 0.32 and P(non-linear) = 0.76). CONCLUSION: The observed association between 25(OH)D and CRP is likely to be caused by vitamin D deficiency. Correction of low vitamin D status may reduce chronic inflammation.