Genes link low vitamin D with multiple sclerosis risk

Researchers have found a possible genetic link between low vitamin D levels and multiple sclerosis; something that has long been suspected, but difficult to prove.

The study, published today in PLoS Medicine shows individuals carrying certain genetic traits that predispose them to having lower vitamin D also have a higher risk of multiple sclerosis; a chronic disease in which the immune system attacks the nervous system.

There is a long-standing hypothesis that low vitamin D and multiple sclerosis are linked, based on studies that compared people's vitamin D levels with their risk of multiple sclerosis.

However these studies don't necessarily show that low vitamin D causes multiple sclerosis; at best, they merely suggest an association that could actually be caused by other factors, says co-author Dr Brent Richards, associate professor at McGill University in Montreal.

"The problem with these sorts of studies is that they are quite likely to be confounded because individuals who use supplements and are concerned about their health in general often undertake other healthy behaviours," says Richards.

"Vitamin D levels may also be related to multiple sclerosis through reverse causation, where individuals with multiple sclerosis or at risk of multiple sclerosis may not be well, they may spend more time indoors and being indoors will decrease their vitamin D levels."

To get around this problem, the team used data from an earlier study of nearly 34,000 people that looked for genetic markers of low vitamin D, and singled out four genetic variants strongly linked with low vitamin D levels.

Then in another group of nearly 14,500 people with MS and 24,000 controls, they looked at the association between these four genetic markers and the risk of multiple sclerosis.

They found that individuals with any one of these genetic markers, and who were therefore vitamin D deficient, were much more likely to have multiple sclerosis.

The study design, called Mendelian randomisation, cuts out the possibility that the effect is related to lifestyle factors, because we have no control over whether or not we inherit those low vitamin D genes, says Richards.

"It's not influenced by lifestyle and also cannot be influenced by reverse causation because if you get multiple sclerosis, this will not change your genes," he says.

The only factor that cannot be ruled out is that these four genetic variants might increase the risk of multiple sclerosis by some other mechanism that has nothing to do with vitamin D.

However the authors say this is highly unlikely, given that each of the four genetic variants separately links low vitamin D levels to multiple sclerosis risk on its own.

Vitamin D research

Dr Lisa Melton, MS Research Australia's Research Development Manager, says the finding is an important link between the observational evidence and the next step, which is testing whether vitamin D supplements can prevent or treat multiple sclerosis.

Such a trial is already underway in Australia and New Zealand, called PrevANZ.

"It's looking at people who have had their first episode, first demyelinating event — which is potentially a precursor to multiple sclerosis — and supplementing those people with one of three doses of vitamin D or placebo … to see whether that supplementation can prevent a second relapse or second event," says Melton.

While the mechanism by which vitamin D levels influence multiple sclerosis risk is not yet understood, the cells of the immune system are known to be responsive to vitamin D.

"We know that vitamin D can modulate the immune system and the evidence show it modulates it in a way that makes the immune system more tolerant, it calms the immune system down, [which] fits with the development of multiple sclerosis," Melton says.