Sophisticated genetics analysis reveals low vitamin D increases MS risk
The majority of studies which attempt to understand if and how environmental exposures such as low vitamin D contribute to the cause of multiple sclerosis are plagued by confounding factors or reverse causation. Confounding means that MS may not actually be caused or linked to vitamin D deficiency, but rather there is another factor in play that is influencing MS risk and is associated vitamin D deficiency that isn't being considered. In terms of reverse causation, this means that people with MS may be spending less time outdoors or experience other effects that reduce levels of vitamin D, making it appear that low vitamin D levels are the culprit when in reality it's the disease that is causing levels to drop. A study recently published in PLOS Medicine by Dr. Brent Richards and colleagues from McGill University uses a powerful technique called Mendelian Randomization (MR) to determine if low vitamin D levels increases risk of developing MS. MR is based on the idea that genes are randomly assigned to you from both of your parents during early development, and so the genes you have are not impacted by outside factors or health conditions. It can be compared to a randomized control trial, where a specific treatment is randomly assigned to a participant, eliminating bias like confounding and reverse causation. By identifying genes that are linked to certain exposures or risk factors, such as low vitamin D, and determining levels of those genes in people with MS, this method can confer a strong rationale that the exposure increases risk of MS.
The researchers identified a number of genetic sequences strongly linked to vitamin D. They observed these genetic sequences among participants in the International Multiple Sclerosis Genetics Consortium study, a genome-wide association study involving up to 14,498 people with MS and 24,091 healthy controls, all of European descent. They found that, among the participants of the International Multiple Sclerosis Genetics Consortium study, lowered vitamin D levels as determined by genetics was strongly associated with increased susceptibility to MS. The MR technique allows the researchers to avoid the possibility of confounding or reverse causation, meaning that the effect of low vitamin D on MS risk is unaffected by other factors such obesity or health status. However, the authors highlight some study limitations (i.e. pleiotropy, or the effect of the genes on other pathways unrelated to vitamin D), and they do not examine whether vitamin D deficiency affects MS disease course or severity.
The study provides compelling evidence that low vitamin D levels increases risk of MS. Ultimately, the outcomes of the study provide impetus for further research to investigate whether increasing levels of vitamin D, through supplementation, diet, or sun exposure, may reduce MS susceptibility. The identification of vitamin D as a causal factor in MS may also have public health implications, since vitamin D insufficiency is common in Canada and taking vitamin D is generally safe and inexpensive. Further, it would be wise to ensure that the family members of individuals with MS ensure that their vitamin D levels are not low. These findings are especially important in countries at higher latitudes such as Canada, which do not receive adequate sun exposure in the winter months to produce vitamin D.
Mokry LE et al. (2015) Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study. PLOS Medicine. Epub ahead of print DOI:10.1016/jexpneurol.2015.05.017.
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