The new research, published in PLOS Medicine, reported that genetically lowered levels of vitamin D – as measured by the level of 25-hydroxyvitamin D (25OHD) – were strongly associated with increased susceptibility to MS.
Led by Brent Richards from McGill University, the research team used a genetic technique called Mendelian randomization to study data from 14,498 people with multiple sclerosis and 24,091 healthy controls taking part in the International Multiple Sclerosis Genetics Consortium study.
The team analysed DNA data from the 33,996 participants and identified four single-letter genetic variants that were closely associated with 25OHD status.
A further comparison between those with and without MS revealed those with genetic variations linked to lower vitamin D were at least twice as likely to have MS.
“Using data from the largest existing genetic consortia, we demonstrate that genetically lowered 25OHD level is associated with an increase in the risk of MS in people of European descent,” wrote the team.
They added that the findings provided a rationale for further investigation into the potential therapeutic benefits of vitamin D supplementation in preventing the onset and progression of MS.
Vitamin D and MS
The team noted that previous observational studies had found an association between decreased vitamin D level and risk of multiple sclerosis (MS), with large scale data also suggesting people living in northern areas of Europe with fewer sunny days have both lower levels of vitamin D and higher risks of MS at population level.
While the data linking low vitamin D status and MS was compelling to some, the nature of many studies had so far made it impossible to show causation.
By studying the genetics of a large group of people, the current study largely avoided the possibility of confounding and reverse causation.
“The identification of vitamin D as a causal susceptibility factor for MS may have important public health implications, since vitamin D insufficiency is common, and vitamin D supplementation is both relatively safe and cost-effective,” said the researchers.
They added that the importance of their findings “may be magnified in high-latitude countries, which have disproportionately higher rates of MS and also higher rates of vitamin D insufficiency”.
Using Mendelian randomization, they identified gene alterations known as single nucleotide polymorphisms (SNPs) that were associated with 25-hydroxyvitamin D (25OHD) levels.
According to the team, four SNPs were genome-wide significant for 25OHD level – with all four SNPs found in or near genes strongly implicated in separate mechanisms influencing 25OHD.
The team then analysed the effect of these SNPs on 25OHD level in 2,347 participants – finding that that the count of 25OHD-decreasing alleles across these four SNPs was strongly associated with lower 25OHD level.
They then analysed the effect of genetically lowered 25OHD on the odds of MS in participants from the International Multiple Sclerosis Genetics Consortium study – which showed that a genetic decrease in the natural-log-transformed 25OHD level by one standard deviation was associated with a two-fold increased risk of MS.
“In practical terms, this finding means that increasing an individual’s circulating 25OHD level by approximately 1.5-fold decreases their odds of developing MS by 50%,” wrote Dr Paolo Muraro from Imperial College London in an ‘Editor’s Summary’ online with the study.
“These findings provide a strong rationale for undertaking randomized controlled trials to investigate whether vitamin D supplementation can prevent the onset and/or progression of MS,” added Muraro.
Source: PLoS Medicine
Published online ahead of print, doi: 10.1371/journal.pmed.1001866
“Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study”
Authors: Lauren E. Mokry, et al