rs9271366
The strongest genetic risk factor for multiple sclerosis
What this position does
This tags an immune tissue type that is the largest single genetic contributor to multiple sclerosis risk. MS also has one of the sharpest latitude gradients of any disease, rising with distance from the equator, which is one of the reasons vitamin D keeps coming up in the research.
Immune system. Shaped by pathogens, and latitude. This is one of the variants that differs sharply between human populations, because something in the environment made one version worth having.
Infection, and the cost of fighting it
For most of human history the commonest way to die young was infection. An immune system tuned to win those fights is tuned for a world that, in rich countries, no longer exists.
What changed: Industry, roughly the last two centuries. Indoor work, heated buildings, refined food, cheap salt and sugar, tobacco at scale, and a collapse in infectious disease. This is where most of the deals in your genome came undone.
Why it spread: a strong case, not settled. There is a clear signal of recent selection and a widely favoured explanation for it, which is not the same as a proven one.
Spiral Staircase, chapter 18: The Immune System's Education Spiral Staircase is written by the same author as this site.
What each result means
| If you carry | What it means |
|---|---|
| No copies of the effect version AA | You do not carry the risk type This tag is absent. |
| One copy AG | You carry one copy Associated with roughly three times the background risk of multiple sclerosis. The background risk is low, so most carriers never develop it. |
| Two copies GG | You carry two copies Associated with roughly six times the background risk, from a low base. This is a tag rather than proper tissue typing. |
Worth knowing. A tag in linkage with the real risk type, and the linkage is weaker outside European populations.
How common each version is
| Ancestry group | G (the effect version) | |
|---|---|---|
| African | 12.6% | |
| American | 6.6% | |
| East Asian | 16.2% | |
| European | 12.2% | |
| South Asian | 25.7% |
1000 Genomes Project phase 3, via Ensembl, retrieved 2026-09-23. These groupings are coarse and flatten a great deal of internal diversity, particularly within Africa. A variant being common somewhere tells you where a piece of your ancestry probably comes from, and nothing else.
How many people carry each result
| Ancestry group | AA | AG | GG |
|---|---|---|---|
| African | 508 / 661 | 139 / 661 | 14 / 661 |
| European | 395 / 503 | 93 / 503 | 15 / 503 |
| East Asian | 358 / 504 | 129 / 504 | 17 / 504 |
| South Asian | 270 / 489 | 187 / 489 | 32 / 489 |
| American | 302 / 347 | 44 / 347 | 1 / 347 |
Counts of people, not modelled frequencies: every one of the 2,504 individuals sequenced by the 1000 Genomes Project phase 3, tallied by the genotype they carry. Deriving these from allele frequencies instead would assume random mating inside each group and undercount the homozygotes.
How to find out which you have
If you have taken a test with 23andMe, AncestryDNA, MyHeritage, Family Tree DNA, TellMeGen or Living DNA, this position is very likely already in the raw data file they gave you. You do not need another test.
One thing to watch if you look it up by hand: testing companies report some positions from one DNA strand and some from the other, and the file does not say which. Read the letters as they appear and you will get the opposite of the truth for some positions. Sequencings resolves that automatically.
Source
Coordinates and allele pair verified against Ensembl GRCh37. Direction of effect verified against VEP protein consequences or 1000 Genomes population frequency. Category: Population adaptation.
Where this fits
Common questions
What is rs9271366?
rs9271366 is a position in the near HLA-DRB1 gene on chromosome 6. This tags an immune tissue type that is the largest single genetic contributor to multiple sclerosis risk. MS also has one of the sharpest latitude gradients of any disease, rising with distance from the equator, which is one of the reasons vitamin D keeps coming up in the research.
What does it mean if I have GG at rs9271366?
You carry two copies. Associated with roughly six times the background risk, from a low base. This is a tag rather than proper tissue typing.
What does it mean if I have AA at rs9271366?
You do not carry the risk type. This tag is absent.
How do I find out my rs9271366 genotype?
If you have taken a home DNA test, this position is very likely in the raw data file you were given. Sequencings reads that file in your browser without uploading it, and resolves which DNA strand each position was reported from, which is the step most manual lookups get wrong.
This is reference information, not medical advice, and not a diagnosis. See the medical disclaimer. Category: Population adaptation.