B4110 - Genetic evidence for the causal relationship between 25OHD and bone fracture a non-linear Mendelian randomization analysis - 18/07/2022

B number: 
Principal applicant name: 
David Hughes | University of Bristol, MRC-IEU (UK)
Dr. Lucy Goudswaard, Madeleine Smith, Nicholas Timpson, Dr Steven Burgess
Title of project: 
Genetic evidence for the causal relationship between 25(OH)D and bone fracture: a non-linear Mendelian randomization analysis
Proposal summary: 

While previous studies have demonstrated no clear effects of vitamin D upon risk of fracture and lowered BMD in the general population, it is clear that vitamin D deficiency causes increased risk of fracture and a reduction in BMD, as is seen in rickets. Further, RCTs of high dose vitamin D have shown a decrease in BMD after administration of vitamin D. This suggests that the effects of vitamin D upon BMD and perhaps fracture are non-linear.

We therefore propose non-linear MR studies of the effect of vitamin D (as measured by 25(OH)D) on BMD and fracture outcomes. Such findings could help to guide future RCTs and provide clinicians with some insights as to the utility of vitamin D administration in different segments of the population.

Impact of research: 
It will help elucidate the impact vitD deficiency has on bone health in the general European population.
Date proposal received: 
Monday, 18 July, 2022
Date proposal approved: 
Monday, 18 July, 2022
Genetic epidemiology (including association studies and mendelian randomisation), Bone disorders - arthritis, osteoporosis, GWAS, Medical imaging, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Bones (and joints), Equipment - MRI, Genetic epidemiology, Mendelian randomisation, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc.