1. Genetically Low Vitamin D Levels, Bone Mineral Density, and Bone Metabolism Markers: a Mendelian Randomisation Study
- Author
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Yun-qiu Hu, Wen-Zhen Fu, J.-W. He, Xiao-Ya Zhang, Yu-juan Liu, Li-hong Gao, Shan-shan Li, and Zhen-Lin Zhang
- Subjects
Adult ,medicine.medical_specialty ,Osteoporosis ,030209 endocrinology & metabolism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Bone remodeling ,03 medical and health sciences ,0302 clinical medicine ,Bone Density ,Internal medicine ,Mendelian randomization ,medicine ,Vitamin D and neurology ,Humans ,030212 general & internal medicine ,Vitamin D ,Aged ,Femoral neck ,Aged, 80 and over ,Bone mineral ,Lumbar Vertebrae ,Multidisciplinary ,Femur Neck ,Confounding ,Mendelian Randomization Analysis ,Middle Aged ,medicine.disease ,Peptide Fragments ,Endocrinology ,medicine.anatomical_structure ,Female ,Biomarkers ,Procollagen - Abstract
Low serum 25-hydroxyvitamin D (25OHD) is associated with osteoporosis and osteoporotic fracture, but it remains uncertain whether these associations are causal. We conducted a Mendelian randomization (MR) study of 1,824 postmenopausal Chinese women to examine whether the detected associations between serum 25OHD and bone mineral density (BMD) and bone metabolism markers were causal. In observational analyses, total serum 25OHD was positively associated with BMD at lumbar spine (P = 0.003), femoral neck (P = 0.006) and total hip (P = 0.005), and was inversely associated with intact parathyroid hormone (PTH) (P = 8.18E-09) and procollagen type 1 N-terminal propeptide (P1NP) (P = 0.020). By contract, the associations of bioavailable and free 25OHD with all tested outcomes were negligible (allP > 0.05). The use of four single nucleotide polymorphisms, GC-rs2282679, NADSYN1-rs12785878, CYP2R1-rs10741657 and CYP24A1-rs6013897, as candidate instrumental variables in MR analyses showed that none of the two stage least squares models provided evidence for associations between serum 25OHD and either BMD or bone metabolism markers (all P > 0.05). We suggest that after controlling for unidentified confounding factors in MR analyses, the associations between genetically low serum 25OHD and BMD and bone metabolism markers are unlikely to be causal.
- Published
- 2016
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