From the Guidelines
There is a genetic link to multiple sclerosis (MS), with certain genetic variations increasing the risk of developing the disease. While MS is not directly inherited like some genetic diseases, genetics do play a significant role in determining susceptibility. People with a first-degree relative (parent, sibling, or child) with MS have a higher chance of developing the disease, compared to the general population. The strongest genetic association is with certain variations in the human leukocyte antigen (HLA) complex, particularly the HLA-DRB1*15:01 allele. However, genetics alone don't determine who develops MS - environmental factors such as vitamin D deficiency, Epstein-Barr virus infection, smoking, and geographical location interact with genetic predisposition. Some studies have shown that psoriasis is more common in MS families than in controls, suggesting a possible genetic connection between the two diseases, as reported in a study published in the Journal of the American Academy of Dermatology 1. Additionally, research has suggested a link between sunlight, vitamin D3, and MS, with lower vitamin D levels associated with a higher risk of MS, as noted in a study published in Clinical Nutrition 1. Key points to consider include:
- Genetic predisposition plays a role in MS susceptibility
- Environmental factors interact with genetic predisposition to influence disease development
- Certain genetic variations, such as the HLA-DRB1*15:01 allele, increase the risk of MS
- MS can occur in families but doesn't follow a simple inheritance pattern
- Non-genetic factors, such as vitamin D deficiency and geographical location, are also important in disease development.
From the Research
Genetic Link to MS
- There is evidence to suggest a genetic link to Multiple Sclerosis (MS), with studies indicating that genetic determinants play a significant role in the etiology of the disease 2.
- Genome-wide association studies have identified over 200 genetic loci associated with MS susceptibility, accounting for almost half of its heritability 3, 4.
- The identified genetic variants are located throughout the genome and are thought to act through cell-specific effects on gene expression and splicing, implicating both adaptive and innate immune cells in the pathogenesis of MS 4.
Genetic Variants and MS Risk
- Over 110 genetic variants have been firmly associated with an increased risk of developing MS, with many of these variants tagging genes involved in the regulation of immune response 2.
- The majority of the identified MS variants are non-coding and seem to act through cell-specific effects on gene expression and splicing, with some variants also mediating risk of other autoimmune and inflammatory diseases 4.
- No single variant is necessary or sufficient to cause MS; instead, each increases total risk in an additive manner, highlighting the importance of polygenicity in MS 4.
Interaction between Genetic and Environmental Factors
- The interaction between genetic and environmental factors in MS is not yet fully understood, with studies suggesting that genetics offers an approach to showing causality for environmental factors through Mendelian randomisation 4.
- Further research is needed to fully decode the genetic complexity of MS and to understand how genetic factors interact with each other and with the environment 2, 3.