Genetic factors in MS: HLA-DRB1, 233 risk genes and what they mean

October 29, 2026

Which genes raise MS risk, what HLA-DRB1*15:01 is, the first gene linked to severity, and the real risk for children and siblings. What science knows today, clearly explained.

One of the questions readers ask me most often is: "Will my child get MS because of me?" The short answer is probably not — but behind it lies one of the most fascinating stories in modern neurology: the story of genes. In this article I've gathered what science really knows today about the genetic factors of multiple sclerosis, from the HLA-DRB1 gene to the newest discoveries about genes that affect how fast the disease progresses.

Genes explain only part of the story

Scientists estimate that genetics accounts for roughly half of the overall risk of MS — the MS Trust cites about 54% [2](#ref-2). The rest comes from environment and lifestyle: Epstein-Barr virus infection, low vitamin D and sunlight, smoking and obesity in adolescence [7](#ref-7). In other words, genes load the gun and the environment often pulls the trigger.

MS is not a hereditary disease in the classic sense, like haemophilia or cystic fibrosis. There is no single "MS gene" passed from parent to child. Instead there are hundreds of small genetic variations, each nudging risk slightly up or down.

HLA-DRB1*15:01 — the strongest known genetic factor

The most important single genetic factor sits in the HLA (human leukocyte antigen) gene group on chromosome 6. These genes help the immune system tell "self" from "foreign" — they show T cells the protein fragments that should be attacked.

The HLA-DRB1*15:01 variant roughly triples the risk of MS in people who carry it [1](#ref-1)[3](#ref-3). Inheriting two copies (one from each parent) raises the risk further. Yet a large share of healthy Europeans carry this variant — most carriers never develop MS.

Interestingly, there are protective variants too. For example, HLA-A*02 is linked to somewhat lower risk [3](#ref-3). That shows a genetic "profile" is not just a sum of bad genes but a balance between factors that raise and lower risk.

233 genetic variants and the immune system

The largest genetic study so far, published in *Science* in 2019 by the International Multiple Sclerosis Genetics Consortium (IMSGC), analysed the DNA of more than 47,000 people with MS and 68,000 healthy controls. It found 233 variants linked to risk: 32 in the HLA region, 200 on other chromosomes and one on the X chromosome [3](#ref-3).

Almost all of these variants act on immune cells — T cells, B cells, microglia — rather than on nerve cells themselves. That is strong evidence MS starts as an immune system disorder. Among the better-known genes are IL7R and IL2RA, which build receptors for signalling molecules called interleukins; their variations raise risk by about 1.5 times [4](#ref-4). Research on IL2RA later helped explain how some immunomodulatory drugs work.

Together, all these variants explain only about half of MS "heritability". Scientists are still looking for the rest.

The first gene linked to disease severity

Until 2023, every gene discovered told us only *who* gets MS, not *how* the disease will behave. That year the IMSGC reported in *Nature* the variant rs10191329 near the DYSF and ZNF638 genes [5](#ref-5). People carrying two copies needed a cane or other walking aid on average about 3.7 years sooner.

This matters for two reasons. First, the gene acts in the brain, not the immune system — suggesting different mechanisms drive progression than drive onset. Second, it opens the door to drugs that protect nerve tissue rather than only calming immunity. For now, this variant is not tested in practice.

Herders, ancient DNA and the history of MS

A study published in *Nature* in 2024 analysed ancient DNA from the bones of thousands of people across Europe and Asia [6](#ref-6). It showed that the genetic variants raising MS risk today arrived in northern Europe around 5,000 years ago with steppe herders (the Yamnaya people).

Those variants probably helped them fight infections caught from livestock. Today, in a world with fewer infections and different lifestyles, the same "strong" immune genes can turn immunity against the body itself. That partly explains why MS is most common in northern Europe.

Genes and environment: the riskiest combination

Genes rarely act alone. Research from a Swedish group showed that people who carry HLA-DRB1*15:01, lack protective HLA-A*02 and smoke have a risk several times higher than people without these factors [7](#ref-7). The same applies when these genes combine with adolescent obesity and past Epstein-Barr virus infection.

Read more about the virus in [Epstein-Barr virus and MS: new evidence](/en/blog/epstein-barr-virus-multiple-sclerosis-new-evidence-2026). The good news is that smoking, vitamin D levels and body weight are things we can influence — even if we can't change our genes.

What is the risk for family members?

These are approximate figures from large family studies [1](#ref-1)[2](#ref-2)[8](#ref-8):

- General population in Europe: about 0.1–0.3%

- Child of a person with MS: about 2–3%

- Brother or sister: about 3–4%

- Non-identical twin: about 5%

- Identical twin: about 25–30%

If an identical twin, who has exactly the same genes, develops MS only in about a third of cases, that is the clearest proof genes are not destiny. Even a child of someone with MS has more than a 97% chance of never developing it. I wrote more about family risk in [Is multiple sclerosis hereditary?](/en/blog/is-multiple-sclerosis-hereditary-genetics-family-risk-science-says-2026).

Should I get a genetic test?

No. There is currently no genetic test that can predict whether someone will develop MS, and none is recommended for diagnosis [1](#ref-1)[8](#ref-8). Even if someone carries HLA-DRB1*15:01, their chance of developing MS remains low. Commercial tests promising an "MS risk score" give no information a doctor would act on.

MS is still diagnosed from symptoms, MRI and, when needed, spinal fluid analysis — following the McDonald criteria. If family risk worries you, talk to a neurologist.

What you can do if MS runs in your family

- Don't smoke, and help your children never start.

- Check your vitamin D and ask your doctor about supplements if it's low.

- Look after children's and teenagers' weight — adolescent obesity raises risk.

- Don't panic over every symptom, but if blurred vision, numbness lasting days or balance problems appear, see a doctor.

Conclusion

MS genetics shows something encouraging: the disease is not written into our genes as a sentence. There are hundreds of small genetic factors, but they only increase susceptibility. Environment, viruses and lifestyle play a huge role — and we can change some of them. New findings, like the severity gene, point toward drugs that could slow progression.

*This article is not a substitute for medical advice. Talk to your neurologist about family risk and any testing.*