SNPwatch: Type 1 Diabetes and Celiac Disease Share Some Genetic Risk Factors

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.

Some families seem to have more than their fair share of illness. This is especially true in families with a propensity for autoimmune diseases, conditions that turn the body’s own infection-fighting cells against it.

Two autoimmune diseases in particular, type 1 diabetes and celiac disease, often cluster together in families, and even in individuals. The prevalence of celiac disease in people with type 1 diabetes is five to 10 times higher than in the general population.

A report published this week by the New England Journal of Medicine shows that shared genetic risk factors are at least partially to blame. According to experts, these findings could help scientists understand more about the underlying biology of both diseases.

The researchers, led by Professor John Todd from the University of Cambridge, tested nine SNPs known to be associated with celiac disease in 8,064 type 1 diabetes patients, 9,339 controls, and 2,828 families with a child affected by the disease.

Four SNPs showed a significant association with type 1 diabetes. Three of these were novel findings. The association of a SNP in the SH2B3 gene with both diseases was already known from previous work.

When the researchers looked in the other direction, testing 19 SNPs known to be associated with type 1 diabetes in 2,560 people with celiac disease and the same 9,339 controls, two significant associations with celiac disease were found.

The total number of cross-acting SNPs was brought to seven when the researchers found that a variation called CCR5delta32 is also associated with the risk of developing both type 1 diabetes and celiac disease. CCR5delta32 is most famously associated with resistance to HIV infection.

Of the variants associated with both type 1 diabetes and celiac disease in this report, all but two had an effect in the same direction – the riskier version for one disease was also riskier for the other.

But the SNPs in IL18RAP and TAGAP had opposite effects. The T version of each SNP increased the risk for celiac disease, but decreased the risk for type 1 diabetes.

A SNP having a different effect on the risk for different diseases is not unheard of. The A version of rs2476601 in PTNP22 increases the risk of type 1 diabetes and rheumatoid arthritis, but has shown to be protective for Crohn’s.

In an accompanying editorial in NEJM, Dr. Robert Plenge suggests that the SNPs identified in this study could theoretically be used to screen patients with one disease (i.e. celiac) to predict their risk of developing the other (i.e. type 1 diabetes). This type of screening, however, is controversial. Plenge also notes that because each SNP contributes only a small increase in risk, their use would not be likely to add much utility to current screening measures.

“The most important implication [of this kind of research] is likely to be the ability to define biologic pathways, many of which are unexpected, that cause disease. Over many years, such insight may lead to the development of novel therapies to treat, prevent, or even cure disease,” Plenge wrote.

23andMe currently reports data for eight SNPs for type 1 diabetes and one SNP for celiac disease in Health and Traits. Overlaps with this study are indicated with an asterisk in the first column. The report by Smyth et al report data for SNP rs45450798 in PTPN2, for which 23andMe does not provide data. We do, however, provide data for rs1893217, which is closely, but not perfectly, linked to rs45450798. The G version of rs1893217 is likely to be equivalent to the G version of rs45450798 as far as increasing risk, but the actual size of the effect may differ. Additional SNPs, including those in this report, will be added to the Health and Traits articles when our scientists are satisfied that the evidence meets our standards.

“Effect” refers to the change in odds of developing the disease per copy of the less common version of each SNP.

SNP Gene Less Common Version Celiac Disease Effect Type 1 Diabetes Effect
rs2816316 RGS1 C 0.72 0.89
rs917997 IL18RAP T 1.29 0.98
rs1738074 TAGAP T 1.21 0.92
* rs3184504 SH2B3 T 1.21 1.28
* rs3087243 CTLA4 A 0.85 0.82
see rs1893217/G rs45450798 PTPN2 G 1.18 1.28
i3003626 CCR5 D=delta32 0.79 0.85

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