In a study led by the MRC Biostatistics Unit at the University of Cambridge, published recently in the Lancet Diabetes and Endocrinology, the Hertfordshire Cohort was among 33 prospective studies comprising 500,962 individuals in which researchers examined associations between 25 hydroxyvitamin D concentrations and cardiovascular and mortality outcomes. These observational analyses suggested inverse associations with incident coronary heart disease, stroke and all-cause mortality outcomes at low 25 hydroxyvitamin D concentrations. Across the range of 25 hydroxyvitamin D concentrations, Mendelian Randomisation analysis using 4 population-based cohort studies, including UK Biobank, comprising 386,406 individuals of European ancestry, demonstrated no associations between genetically determined 25 hydroxyvitamin D levels and these outcomes. However, in stratified analyses in the population with 25 hydroxyvitamin D levels less than 25 nmol/l, genetically determined 25 hydroxyvitamin D was inversely associated with all-cause mortality. These exciting and novel findings provide support for a causal relationship between 25 hydroxyvitamin D concentrations and mortality in those who are vitamin D deficient but not in the wider population.

“These novel findings demonstrate the huge value in such large-scale collaborative approaches combining a wide range of cohort resources, and provide the basis for more nuanced intervention studies and potentially for novel approaches to disease prevention.”

Professor Cyrus Cooper, Director and Professor of Rheumatology, who led the MRC LEC contribution

The manuscript is available here: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00263-1/fulltext

The accompanying commentary is available here: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00282-5/fulltext