From the Guidelines
Multiple sclerosis (MS) is not purely genetic but has a complex inheritance pattern with both genetic and environmental factors. While MS is not directly inherited like some diseases, genetics do play a significant role in determining susceptibility, as noted in a recent study published in 2025 1. People with a first-degree relative (parent, sibling) with MS have approximately a 3-5% chance of developing the condition, compared to about 0.1% in the general population. The strongest genetic association is with certain human leukocyte antigen (HLA) genes, particularly HLA-DRB1*15:01, which can increase risk by threefold. However, genetics alone don't determine who develops MS - environmental factors such as vitamin D deficiency, Epstein-Barr virus infection, smoking, and geographical location (with higher rates in areas farther from the equator) significantly influence disease development. This explains why even identical twins, who share 100% of their genes, only have a 25-30% concordance rate for MS, demonstrating that non-genetic factors are crucial in triggering the disease in genetically susceptible individuals. Some studies have investigated the risk of developing progressive multifocal leukoencephalopathy (PML) in MS patients treated with natalizumab, but this is not directly related to the genetic basis of MS itself 1. Key points to consider include:
- Genetic factors play a role in MS susceptibility, but do not solely determine the development of the disease
- Environmental factors significantly influence disease development
- The strongest genetic association is with certain HLA genes, particularly HLA-DRB1*15:01
- Identical twins have a 25-30% concordance rate for MS, highlighting the importance of non-genetic factors.
From the Research
Genetic Contribution to Multiple Sclerosis
- The genetic contribution to the risk of developing multiple sclerosis (MS) is estimated to be about 50%, with the genes involved mainly located within the major histocompatibility complex 2.
- Genome-wide association studies (GWAS) have uncovered more than 200 implicated genetic loci, revolutionizing the genetics of multiple sclerosis 3.
- The disease is likely caused by a complex interaction between multiple genes and environmental factors, leading to inflammatory-mediated central nervous system deterioration 4.
Familial Multiple Sclerosis
- Familial MS represents 12.6% of all MS cases, with the risk depending on the degree of genetic proximity to the index case 2.
- Familial cases seem to have a different clinical presentation from sporadic cases, such as earlier worsening of disability and more severe long-term disability 2.
- Clinical correlations between different members of a family with MS have also been described, such as a similar age of onset between siblings 2.
Genetic Research and Findings
- Advances in technology and novel models for collaboration have enabled the discovery of more than 50 non-HLA genetic risk factors associated with MS 4.
- The association with alleles of the major histocompatibility complex (MHC) has been established, but no major susceptibility gene has been identified through full genome screens 5.
- Current studies are geared towards identification of causal alleles, associated pathways, epigenetic mechanisms, and gene-environment interactions 4.