In autoimmune disorders, the immune system — which normally protects us from harmful, foreign substances — goes into overdrive and starts attacking the body’s own cells, causing inflammation and organ damage.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic, widespread inflammation that can result in arthritis, fever, skin rashes, muscle aches, seizures and fatigue, among other symptoms. Some symptoms can even be life-threatening. Between one and seven out of every 10,000 people is affected by SLE. The disease affects women nine times more frequently than men, and tends to be more prevalent and severe in people of non-European descent. The exact causes of SLE are unknown and there is currently no cure.
For several decades now, researchers have probed the genetic underpinnings of this mysterious disease. Two studies published this week in Nature Genetics identify new genetic variants associated with SLE in European and Asian populations.
In the first study, a team led by Vesela Gateva and Robert Graham of Genentech identified ten novel genetic variants associated with SLE in a European group consisting of more than 3,000 people with the disease and 10,000 people without SLE. Half of these variants were previously associated with other autoimmune diseases, but this is the first time they have been associated with SLE. In addition, the researchers confirmed nine variants previously linked to SLE in other studies.
(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service by using the Browse Raw Data feature. See table at the end of this post.)
Of the previously reported autoimmune variants, Gateva and colleagues note that the A version of rs641153, a known risk variant for age-related macular degeneration, seems to be protective against SLE, although additional research will be needed to confirm this effect.
One of the SNPs not previously associated with SLE or any other autoimmune disease, rs7708392, is in the gene that encodes TNIP1. The TNIP1 protein is known to interact with TNFAIP3, a protein that genetic studies have previously linked to rheumatoid arthritis, psoriasis and type 1 diabetes — all autoimmune disorders — suggesting that the TNIP1-TNFAIP3 association may play a general role in autoimmunity.
(23andMe does not currently report data for rs7708392.)
In the second study, Jian-Wen Han and Xue-Jun Zhang’s team from Anhui Medical University in China identified 21 genetic variants associated with SLE in more than 4,000 Chinese individuals with the disease and 8,200 individuals without autoimmune disorders. About half of the associations confirmed previous reports in European populations, and half represented novel findings.
Interestingly, one of the new variants they identified — rs10036748 — is also in the TNIP1 gene. Here, each copy of a T increased odds of SLE by about 1.24 times. Many other SNPs associated with SLE in the Chinese study were located in or near genes involved in immune response.
The TNIP1-TNFAIP3 connection and association of variants known to be linked to other autoimmune diseases add to growing evidence that common genetic factors contribute to autoimmunity. These findings may help pave the way for novel therapeutics for autoimmune disease that exploit this shared genetic basis.
Novel SNPs associated with SLE in Europeans (Gateva et al. study)
|rs1990760||T||1.17||Previously linked to type 1 diabetes and Graves’ disease.|
|rs641153||G||1.30||Previously linked to age-related macular degeneration.|
|rs12708716||A||1.16||Previously linked to type 1 diabetes, Addison’s disease, and multiple sclerosis.|
|rs6887695||G||1.13||Previously linked to psoriasis and irritable bowel disease.|
Novel SNPs associated with SLE in Asians (Han et al. study)
|rs1234315||T||1.37||Also associated in Europeans|
|rs2205960||T||1.46||Also associated in Europeans|
|rs7574865||T||1.51||Also associated in Europeans|
|rs10036748||C||0.81||In TNIP1 gene|
|rs548234||C||1.25||Also associated in Europeans|
|rs2230926||G||1.72||In TNFAIP3 gene, also associated in Europeans|
|rs4728142||A||1.43||Also associated in Europeans|
|rs7812879||T||0.69||Also associated in Europeans|
|rs2618479||A||0.72||Also associated in Europeans|
|rs2248932||G||0.76||Also associated in Europeans|
|rs463426||C||0.78||Also associated in Europeans|
|rs131654||G||0.78||Also associated in Europeans|