"In previous studies, a close statistical relationship has been established between low vitamin D levels and increased mortality rates," explained study coauthor Børge Nordestgaard, who is a Clinical Professor at the Faculty of Health and Medical Sciences, University of Copenhagen, and Chief Physician at Copenhagen University Hospital. "However, the fact that vitamin D deficiency can be a marker for unhealthy lifestyles and poor health in general may have distorted the results. This led to our current study, which was based on an examination of the participants' genes - genes which cannot be explained by unhealthy lifestyles."
The investigation included 95,766 participants in the Copenhagen City Heart Study, the Copenhagen General Population Study and The Copenhagen Ischemic Heart Disease Study. Over the studies' median follow-up times of 19.1, 5.8 and 7.9 years, 10,349 deaths occurred. After evaluating the association between 25-hydroxyvitamin D levels and mortality over follow-up, Dr Nordestgaard and colleagues analyzed the relationship between genotypes that decrease plasma vitamin D and the risk of mortality.
"We have conducted a major Danish study, in which we have examined the connection between genes associated with permanent low levels of vitamin D and mortality," reported Dr Afzal. "We can see that genes associated with low vitamin D levels involve an increased mortality rate of 30 percent and, more specifically, a 40 percent higher risk of cancer-related deaths. An important factor in our study is that we have established a causal relationship."
"What is mendelian randomisation, and why might it be better than classical observational epidemiology?" ask Paul Welsh of the British Heart Foundation and Naveed Sattar in an accompanying editorial. "We now know that approaches linking circulating 25-hydroxyvitamin D [25(OHD)] to health outcomes are seriously hampered by confounding and reverse causality. The circulating concentration of 25(OH)D is influenced by factors such as time spent outdoors, diet, adiposity, smoking, and acute phase response. Mendelian randomisation attempts to eliminate such problems by exploiting the random allocation of genetic material at conception."
Since several trials of vitamin D supplementation will begin reporting in 2017, Drs Welsh and Sattar note that "We do not have to wait too long to see whether mendelian randomisation studies and large scale trials are in agreement."