Circulating Serum 25-Hydroxyvitamin D Levels and Bone Mineral Density: Mendelian Randomization Study

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Susanna C LarssonKarl Michaëlsson

Abstract

There is considerable discussion of the importance for increased serum 25-hydroxyvitamin D (S-25OHD) concentration associated with adequacy for bone health. Accordingly, whether long-term high S-25OHD concentration in general positively affects bone mineral density (BMD) is uncertain. We used a Mendelian randomization design to determine the association between genetically increased S-25OHD concentrations and BMD. Five single-nucleotide polymorphisms (SNPs) in or near genes encoding enzymes and carrier proteins involved in vitamin D synthesis or metabolism were used as instrumental variables to genetically predict 1 standard deviation increase in S-25OHD concentration. Summary statistics data for the associations of the S-25OHD-associated SNPs with dual-energy X-ray absorptiometry (DXA)-derived femoral neck and lumbar spine BMD were obtained from the Genetic Factors for Osteoporosis (GEFOS) Consortium (32,965 individuals) and ultrasound-derived heel estimated BMD from the UK Biobank (142,487 individuals). None of the SNPs were associated with BMD at Bonferroni-corrected significance level, but there was a suggestive association between rs6013897 near CYP24A1 and femoral neck BMD (p = 0.01). In Mendelian randomization analysis, ...Continue Reading

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