New genetic clues to MS

Thursday August 11 2011

“Scientists have discovered 29 new gene variants that are implicated in multiple sclerosis,” The Guardian has today reported.

These genetic variants were identified in an international project reported to be the largest genetics study ever undertaken in people with multiple sclerosis (MS), involving more than 27,000 participants. The project’s researchers compared the DNA of people with MS to that of people without it, looking for genetic variants (genetic differences) which might make people susceptible to the disease. The research also confirmed 23 previously known genetic associations found in earlier studies.

A large number of the genetic variants implicated in this research are close to sections of DNA involved in regulating the immune system, supporting the theory that MS is an autoimmune disease (one in which the immune system attacks parts of the body – in this case, the brain and spinal cord). Overall, this large study provides a useful contribution to understanding the genetic basis of MS and could further scientists’ understanding of the biological mechanisms which cause it. However, further research is needed to confirm the role of these genetic variants and to identify the relative importance of other genetic and environmental risk factors.

Where does the story come from?

The study was carried out by researchers from various scientific and academic centres, including the Universities of Oxford and Cambridge. The 250 researchers involved were members of the International Multiple Sclerosis Genetics Consortium, a collaboration between various research projects sharing data and resources so that a large-scale genetic analysis of MS patients could be performed. The study was funded by the Wellcome Trust and published as a letter article in the peer-reviewed scientific journal Nature.

The Guardian’s reported the study fairly and included comments from an independent expert. Its headline that new “genes” linked to MS had been discovered was technically incorrect, however. The researchers found genetic variants which lie close to genes (rather than within them), which may or may not contribute to the disease. The fact that these were not single new genes is important to note as their pattern of inheritance will be different.

What kind of research was this?

Multiple sclerosis (MS) is a disorder of the nervous system, affecting 2.5 million people worldwide. People with MS experience damage to the nerve fibres in the brain and spinal cord, as well as the “myelin sheath”, a protective layer found around nerve fibres. This damage eventually results in difficulty with functions of daily living. MS is thought to be an autoimmune disease (a condition in which the immune system attacks parts of the body). Both genetic and environmental risk factors are known to be involved in its development.

The researchers point out that although previous studies have suggested that some genetic variants have a role in susceptibility to the disease, most of the “genetic architecture” of MS has yet to be defined. To do so requires an analysis of a large sample of people with MS, beyond the numbers currently available to individual research groups. This collaborative gene-wide association study pooled data from 23 research groups to allow an analysis of DNA from large numbers of people across fifteen countries.

This was a genome-wide association study, a type of case control study, in which researchers compared the DNA from people with MS to that from healthy adults. It looked for genetic variants that might be associated with an increased risk for MS. This is an appropriate study design for addressing this question.

What did the research involve?

The researchers compared the DNA of 9,772 people with MS who had been diagnosed according to internationally accepted criteria with that of 17,376 unrelated healthy adults. All the people in the study were drawn from populations with European ancestry to minimise the chance that ethnic differences would affect the results. In most centres, the researchers extracted DNA from blood samples, but they also took some from cell lines or saliva.

Using standard genetic technology, the researchers scanned the genetic make-up of cases and controls. After quality control was applied, the researchers found that across all the DNA extracted they had 465,434 autosomal SNPs (single letter variations in the genetic code) available for analysis. The researchers used their analysis to identify the variants that were more or less common in the cases than the controls.

Rather than looking for associations across the whole dataset (which would be an extremely complex and time-consuming task), they first looked for associations with MS within samples from the UK. The associations identified were then tested or validated by the other research groups. This is a standard practice in large-scale genetic analyses.

What were the basic results?

The researchers identified 29 new genetic variants associated with the disease, with an additional five variants also thought to increase the risk of developing the disease. They also confirmed 23 previously known genetic associations.

Many of the variants identified are close to genes involved in regulating the immune system, in particular the function of T-helper-cells (a type of white blood cell involved in fighting infection) and interleukins (chemicals that communicate between different immune system cells). The researchers also identified two genetic variants involved in processing vitamin D.

They did not find genetic variants associated with determining the severity or course of the disease, nor did they find variants associated with gender or with month of birth (one theory is that people born in certain months of the year are at a higher risk of MS).

How did the researchers interpret the results?

The researchers concluded that they have enhanced the understanding of genetic susceptibility to MS, in particular the role of the immune system. They said that this will help researchers understand the biological mechanisms underpinning the disease, and has implications for future treatment strategies.


This large genome-wide study has identified some new genetic variants associated with an increased risk of developing MS. The strength of this study lies in its size and in the fact that the researchers were able to verify findings in a wide range of countries. However, further research is required to confirm whether these genes play a role in the development of this disease, and (particularly as they lie outside of genes) how they might do so. Future studies will need to look at how these variants might interact with environmental risk factors, which are also known to play a role in the condition.

Where multiple variants are found, it is likely that each only contributes a small amount to the risk of developing the disease, and this means that the way that the disease risk is inherited will be complex. While it is possible that knowledge gained in this study could lead to developing new treatment strategies, more research is needed before scientists can be certain of the role of these variants and the way they affect the body.

Analysis by Bazian
Edited by NHS Choices