SNPwatch: Researchers Investigate Shared Genetic Factors for Autoimmune Diseases

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

By Bethann Hromatka

Autoimmune diseases are caused by an overactive immune system. In these diseases, white blood cells, which normally help your body fight infections, ramp up and attack your own cells and organs. These disorders can be very debilitating and are relatively common, affecting roughly 1 in 20 individuals. Some well-known examples include psoriasis, Crohn’s disease, celiac disease, multiple sclerosis, systemic lupus erythematosus (or lupus), type 1 diabetes, and rheumatoid arthritis. Although most of these disorders manifest in different parts of the body, all are characterized by excess inflammation.

Our understanding of the causes of immune disorders has been limited due to their complexity. These diseases are not caused by changes in a single gene, but are influenced by many genes as well as environmental and lifestyle factors. For example, mutations in at least 22 different genes have been linked to type 1 diabetes to date. At the same time, it is well known that non-genetic factors can increase or decrease a person’s risk of developing this disease.

An interesting observation about autoimmune diseases is that they tend to run in families. For instance, a mother with type 1 diabetes might have a daughter with celiac disease. Or, someone with Crohn’s disease might also develop celiac disease or psoriasis. There also appears to be a pharmacological link—for example the VGX™-1027 drug is used to treat both rheumatoid arthritis and type 1 diabetes. These observations have led researchers to wonder if there could be a common genetic basis to autoimmune diseases.

A recent study published in PLoS Genetics on behalf of the FOCiS Network of Consortia tested this very hypothesis: do some mutations put an individual at risk for more than one autoimmune disease? To address this question, the researchers looked at previously published genome wide association studies (GWAS) and compiled a list of 107 SNPs1 that associated with at least one of seven immune diseases. Then, they applied a new statistical method to identify SNP versions that were linked to multiple autoimmune diseases.

The authors reported that nearly half of the SNPs influenced risk for at least two autoimmune diseases. In most cases, the same version of the SNP was associated with higher risk for each disease. For example, the T version at , the G version at , and the A version at are associated with higher odds for multiple diseases (see table at the end of this post for details). Interestingly, 9 SNPs (including , , , ) were simultaneously associated with higher odds for one disease and lower odds for a different disease. One SNP— in the SH2B3 gene—was associated to varying degrees with all seven diseases; the C version was risky for celiac disease and multiple sclerosis, but protective for psoriasis, rheumatoid arthritis, lupus, Crohn’s disease and type 1 diabetes.

(23andMe customers can view their data for these SNPs and results for available Health reports in their accounts using the table at the end of this post.)

The authors also found that certain SNPs grouped together based on their disease associations. For example, SNPs associated with both Crohn’s disease and psoriasis formed a distinct cluster and those linked to both rheumatoid arthritis and type 1 diabetes also comprised a distinct cluster. In many cases, SNPs in a particular group were located in genes involved in the same biological processes. These results suggest that shared genetic factors can point to the underlying cellular pathways that are disrupted in different classes of immune disorders.

These findings are exciting because they point to a common genetic basis to autoimmune diseases. Understanding the genetic relatedness of diseases could help researchers develop new therapies to target common cellular pathways or redirect currently available treatments to a genetically related disease. Similarly, the approach used in this paper could be applied to other classes of complex diseases, such as psychiatric disorders, to determine if they also share common genetic components.

Table: SNPs associated with multiple autoimmune diseases

SNP Gene Region Version Increased Risk Decreased Risk Relevant 23andMe Health Reports
CCR1 T Celiac Disease, Type 1 Diabetes Celiac Disease
PTPN2 G Rheumatoid Arthritis, Crohn’s Disease, Celiac Disease, Type 1 Diabetes Crohn’s Disease, Type 1 Diabetes
* STAT4 A Rheumatoid Arthritis, Lupus, Type 1 Diabetes Lupus, Rheumatoid Arthritis
IFIH1 C Lupus, Type 1 Diabetes Type 1 Diabetes, Selective IgA Deficiency
IL2-IL21 T Rheumatoid Arthritis Celiac Disease Celiac Disease
PTPN22 A Rheumatoid Arthritis, Lupus,Type 1 Diabetes Crohn’s Disease Rheumatoid Arthritis, Type 1 Diabetes, Hashimoto’s Thyroiditis, Generalized Vitiligo
CTLA4 A Celiac Disease Rheumatoid Arthritis, Type 1 Diabetes Type 1 Diabetes
** IL12B T Psoriasis, Lupus Crohn’s Disease Psoriasis
SH2B3 C Multiple Sclerosis, Celiac Disease Rheumatoid Arthritis, Lupus, Crohn’s Disease, Type 1 Diabetes Type 1 Diabetes

* is highly correlated with , which is mentioned in the Lupus and Rheumatoid Arthritis Established Research reports
** is equivalent to reported in the study.
1 The authors did not include SNPs in the Major Histocompatibility Complex (MHC), which contains genes for proteins used by the immune system to recognize foreign molecules. Variations in this region of the genome are already established as being linked to multiple immune diseases.

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SNPwatch: Researchers Identify Risk Variants Shared by Crohn’s Disease and Celiac Disease
SNPwatch: Type 1 Diabetes and Celiac Disease Share Some Genetic Risk Factors
SNPwatch: New Variants Associated With Lupus in Europeans and Asians
SNPwatch: Three New Genetic Variants Associated With Rheumatoid Arthritis Risk

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.