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Genome Study Finds 13 New Celiac Disease-associated Gene Markers


Nature Genetics celiac genome study

Celiac.com 08/25/2010 - The revolution in genetic studies continues to drive discoveries about the genetic triggers for celiac disease. In recent developments, a genome-wide association study (GWAS) has nearly doubled the number of single-nucleotide polymorphisms (SNPs) associated with celiac disease from 14 to 27, most of which contain genes related to immune functions.

Doctors have known for some time now that people with genetic markers DQ2 and DQ8 are more susceptible to celiac disease than those without those gene markers. This fact points to the importance of histocompatibility complex presentation of gluten antigens to immune cells.

In 2007, a landmark study established 14 celiac-associated SNPs. Recently, a team of researchers conducted a comprehensive follow-up to that study. The study team included P. C. Dubois, G. Trynka, and L. Franke. The resulting GWAS used six times more genetic samples than the 2007 study, including five European case-control data sets comprised of 4,533 celiac disease patients and 10,750 controls. In all, the team tested nearly 300,000 genes.

Based on low P values (P < 5 × 10-8) and biological likelihood of candidate SNPs being related to immune function, the team selected a total of 131 single-nucleotide polymorphisms (SNPs) for replication in an independent cohort of 4918 cases and 5684 controls. Their data identify 13 additional regions associated with celiac disease.

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To determine the trigger gene for each potential locus, the team used three complementary, objective methods. They first used a computerized algorithm, known as GRAIL, that searches PubMed for specific terms related to various gene features. They next employed what is called expression quantitative trait locus mapping, which isolates variations that may influence the expression of the gene, rather than its protein structure and function. Lastly, they looked for co-expression of gene clusters in suspect candidate genes relative to known susceptibility loci. Each of these methods shed additional light on the association between suspect SNPs and celiac disease susceptibility.

However, the authors of the study go out of their way to note that, ultimately, the authors categorized loci and predicted causal genes using their "own knowledge of celiac disease pathogenesis.” This fact, they point out, emphasizes the crucial role played by knowledgable scientists exercising their insights to reap the most benefit from ‘objective’ advanced genomic data mining technologies.

This study involved genetic assessment in a very large cohort, replication in a similarly large cohort, and multiple independent approaches at refining candidate SNPs. As a result, the number of known loci of celiac disease susceptibility genes has increased from 14 to 27. Their findings also identify several new pathways of celiac disease pathogenesis that merit further investigation.

The study team also notes that these findings only account for 20% of the variance in celiac disease heritability. This, they say, points to a need for additional studies regarding genetic triggers for celiac disease.

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Only GIs can order a complete celiac panel at Kaiser. Your results look negative, but those are just "screening" results. You are not IgA deficient (used only as a control test for celiac disease) so that means the TTG IgA test worked. If you suspect celiac disease, ask for a GI referral. Keep eating gluten!!!! If you go gluten free then all the celiac tests will be invalid. You should rule out other issues like Crohn's, SIBO, etc based on your symptoms and health history. I would ask for a complete celiac panel from the GI. Why? Not all celiacs test positive to the TTG which is a cheaper, but excellent test but does not catch all celiacs like me!!!

Ditto. However, this is what I can never understand about gluten free food. (see the bold bits which I've taken from the article) "We wanted to determine if gluten consumption will affect health in people with no apparent medical reasons to avoid gluten. Gluten-free foods often have less dietary fiber and other micronutrients, making them less nutritious and they also tend to cost more,? I wonder why what so much of what I eat that's gluten free doesn't have added vitamins - we of all people need fortification in our cereals and bread, surely?

Yeah we learned that the hard way. I am inclined to think (as I did initially) that it was JUST the Cheerios but as time is passing and she is not bouncing back I am worried that we need to strip away dairy again for a while.

Oh I have no issue with being dairy free personally but tell that to a 13 year old. We both went gluten-free at the same time and it has been mindlessly easy for me. But I am easy about food and no real food issues. I am far more adaptable. She comes to the table with her own unique set of issues that complicate just easily transitioning to dairy free versions of much loved favorites. To most they are jst that "substitutes" to her they are completely different foods and ones that she has no interest in eating. They don't satisfy her need for XYZ. It is like craving an apple and someone handing you a fish. For her anyway! LOL!

I believe the talk around this forum is that cheerios are not gluten free enough for people with celiac at this time. I don't know if anything has changed on that and when their lawyer calls me I'll quickly delete this. haha