Markers / Condition
Which genes are linked to autoimmune disease?
Autoimmunity is the immune system, built to deal with parasites and bacteria, turning on the body instead. Several of the strongest risk variants are found in Europeans and essentially nowhere else, which is one of the reasons autoimmune disease rates differ so much between populations. The usual explanation is that a more aggressive immune system was worth having when infection was the main thing that killed you.
The markers
| Marker | Gene | What it does | Evidence |
|---|---|---|---|
| rs2476601 | PTPN22 | The autoimmunity variant that Europeans have and others do not | established |
| rs11209026 | IL23R | A protective variant for Crohn's disease | established |
| rs2066844 | NOD2 | NOD2, the first Crohn's gene ever found | established |
| rs3184504 | SH2B3 | One variant, coeliac disease, blood pressure and defence against bacteria | established |
| rs9271366 | near HLA-DRB1 | The strongest genetic risk factor for multiple sclerosis | strong |
| rs2187668 | HLA-DQA1 | Coeliac disease risk type | strong |
| rs1800629 | TNF | Tumour necrosis factor, the inflammation dial | moderate |
| rs1143634 | IL1B | Interleukin-1 beta, the fever signal | moderate |
The autoimmunity variant that Europeans have and others do not
rs2476601 · PTPN22
PTPN22 sets the threshold at which immune cells activate. The variant version lowers it. It is a risk factor for rheumatoid arthritis, type 1 diabetes, lupus and several other autoimmune conditions, it is carried by roughly one European in ten, and it is essentially absent from East Asian and African populations. Whatever it was useful against, it is now a liability.
Two copies: You carry two copies
A protective variant for Crohn's disease
rs11209026 · IL23R
Most variants raise risk. This one lowers it, substantially, for Crohn's disease and for psoriasis and ankylosing spondylitis. It is carried by about one European in sixteen and is essentially absent elsewhere. It also pointed drug developers straight at the IL-23 pathway, which is now the target of several real medicines.
Two copies: You carry two protective copies
NOD2, the first Crohn's gene ever found
rs2066844 · NOD2
NOD2 senses a fragment of bacterial cell wall inside your own cells. The variant version senses it less well, and the gut's relationship with its bacteria goes wrong. This was the first gene ever linked to a common inflammatory disease by genetics, and like PTPN22 it is a European variant, absent from East Asian populations where Crohn's disease is caused differently.
Two copies: You carry two copies
One variant, coeliac disease, blood pressure and defence against bacteria
rs3184504 · SH2B3
A striking example of one change doing several things at once. The same variant raises risk of coeliac disease, type 1 diabetes and higher blood pressure, and it also produces a stronger response to bacterial infection. The favoured explanation is that the infection benefit was worth the rest, in a world where infection killed you young.
Two copies: You carry two copies
The strongest genetic risk factor for multiple sclerosis
rs9271366 · near HLA-DRB1
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.
Two copies: You carry two copies
Coeliac disease risk type
rs2187668 · HLA-DQA1
Coeliac disease requires a specific immune receptor type to be possible at all. This position tags the main one, HLA-DQ2.5. Its real value is the negative: without a permitting type, coeliac disease is very nearly ruled out.
Two copies: DQ2.5 present, two copies
Tumour necrosis factor, the inflammation dial
rs1800629 · TNF
TNF is one of the body's strongest inflammatory signals, and blocking it is the basis of several major drugs for rheumatoid arthritis and inflammatory bowel disease. This promoter variant is associated with producing more of it.
Two copies: You carry two higher-output copies
Interleukin-1 beta, the fever signal
rs1143634 · IL1B
IL-1 beta is the molecule that raises your body temperature during infection. Fever is a defence, not a symptom, and this variant is associated with producing more of the signal that triggers it.
Two copies: You carry two higher-output copies
Which versions do you carry?
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Read my fileCommon questions
Which genes are linked to autoimmune disease?
Autoimmunity is the immune system, built to deal with parasites and bacteria, turning on the body instead. Several of the strongest risk variants are found in Europeans and essentially nowhere else, which is one of the reasons autoimmune disease rates differ so much between populations. The usual explanation is that a more aggressive immune system was worth having when infection was the main thing that killed you. The markers most often cited are rs2476601 in PTPN22, rs11209026 in IL23R, rs2066844 in NOD2, rs3184504 in SH2B3, rs9271366 in near HLA-DRB1.
What does rs2476601 do?
PTPN22 sets the threshold at which immune cells activate. The variant version lowers it. It is a risk factor for rheumatoid arthritis, type 1 diabetes, lupus and several other autoimmune conditions, it is carried by roughly one European in ten, and it is essentially absent from East Asian and African populations. Whatever it was useful against, it is now a liability. Carrying two copies: you carry two copies.
What does rs11209026 do?
Most variants raise risk. This one lowers it, substantially, for Crohn's disease and for psoriasis and ankylosing spondylitis. It is carried by about one European in sixteen and is essentially absent elsewhere. It also pointed drug developers straight at the IL-23 pathway, which is now the target of several real medicines. Carrying two copies: you carry two protective copies.
What does rs2066844 do?
NOD2 senses a fragment of bacterial cell wall inside your own cells. The variant version senses it less well, and the gut's relationship with its bacteria goes wrong. This was the first gene ever linked to a common inflammatory disease by genetics, and like PTPN22 it is a European variant, absent from East Asian populations where Crohn's disease is caused differently. Carrying two copies: you carry two copies.
What does rs3184504 do?
A striking example of one change doing several things at once. The same variant raises risk of coeliac disease, type 1 diabetes and higher blood pressure, and it also produces a stronger response to bacterial infection. The favoured explanation is that the infection benefit was worth the rest, in a world where infection killed you young. Carrying two copies: you carry two copies.
Reference information, not medical advice and not a diagnosis. See the medical disclaimer.