Genetics in MS

The ultimate cause of multiple sclerosis (MS) is still unknown. Probably a combination of hereditary factors, an environmental trigger and a defect in the immune system will lead to MS. The frequency of MS varies geographically and between ethnic groups, with the greatest risk in white northern Europeans living in temperate regions. From family studies it has been known for many years that genes plays a role, and that MS susceptibility is influenced by genetic variations within the major histocompatibility complex (MHC).

We have previously performed linkage studies investigating Danish and Nordic sib pair families, and participated in the ultimate MS linkage study investigating more than 700 European MS families, that revealed MHC as the only genome-wide linkage signal in MS with a lod score of 11.7, dominated by the DR2 (DRB1*15:01-DQB1*06:02) haplotype.

We have collected DNA for more than 15 years, and today we have DNA from more than 1,800 Danish MS patients and 1,200 controls, all kept in the “Danish Multiple Sclerosis Biobank” in DMSC. In order to increase the sample size for genetic testing, we have participated in the “Nordic MS Genetic Network” since 1994, and today the Nordic material consists of more than 6,000 MS cases and 6,000 controls. The research in DMSC is focused on the candidate gene approaches and the genetic influence on the differences in treatment response.

We are part of the IMSGC (International Multiple Sclerosis Genetic Consortium) – and the Wellcome Trust Case Control Consortium (WTCCC), where 23 research groups from 15 countries are performing the largest set of MS genome-wide association study (GWAS), genotyping 11,000 cases and 11,000 controls using 500,000 SNP chip. Primary results have elucidated associations to more than 100 gene variations (SNPs). Following this collaboration we are joining the Immunochip Consortium, where 1,000 Danish cases and 1,000 Danish controls participate in a large scale genetic analysis, investigating best genes/regions/SNPs in MS together with other international MS research groups and 9 other autoimmune diseases research groups, looking for shared autoimmune genes.

The risk of MS has been increasing over the last 50 years, especially among women older than 40 years. On this background we have initiated a project looking at aspects of gender differences, including different treatment responses.

Furthermore, we have initiated a large-scale vitamin D project, investigating gene variations within the vitamin D pathway, and the importance of vitamin D in clinical and immunological disease activity.

In addition, we have collected more than 800 questionnaires from MS patients dealing in detail with lifestyle and environmental exposure for a project studying gene-environmental interactions.