Learn the science, history, and facts before starting your Gluten ID journey.
CELIAC GENETICS MADE EASY
The Gluten ID Wheel was designed by Targeted Genomics to make celiac genetic health risk accessible to individuals, families, and physicians with a one time test. Using a simple cheek swab, the Gluten ID i) inheritance and ii) spectrum of risk are identified and reported in an understandable format.
Megiorni F, et al. (2009) "HLA-DQ and risk gradient for celiac disease." Human Immunl 70:55-59.
In genetically susceptible individuals, exposure to gluten proteins can trigger an abnormal immune response affecting the GI tract and other body systems.
Biopsy findings of prolonged damage to the small intestine is the gold standard for diagnosis of celiac disease. The damage can be reversed with a gluten free diet.
Most individuals with celiac risk genetics never develop celiac disease.
First degree relatives (parents, siblings, children) of individuals with celiac disease have approximately 5%-20% risk (compared to 1% for the general population) of developing celiac disease. The shared increase in risk may be attributed to genetic inheritance, shared lifestyle, and other factors.
Individuals with other autoimmune conditions such as Hashimotos thyroiditis, Sjorgrens syndrome, and Type I Diabetes have slightly increased risk compared to the general population (approximately 5% versus 1%) for development of celiac disease. The prevalence of celiac disease is also higher in the presence of certain congenital disorders including Downs and Williams Syndrome.
Although alterations in genes other than HLA-DQA1 and HLA-DQB1 have been investigated in celiac disease research, none have sufficient level of evidence to be used clinically for celiac genetic risk assessment.
TIMELINE
Celiac disease is believed to have developed over 8,000 years ago when hunter/gatherers began encountering new types of food (including wheat) during the neolithic period agricultural revolution. However it wasn’t until the first century AD that a Greek physician named Aretaeus of Cappadocia identified the symptoms as a disease of the “koelia” or abdomen in Greek. Before the true trigger for celiac disease was identified many treatments and diets were tried, including strict rice, mussel, and even banana diets. It wasn’t until the 1970s-1990s that celiac disease was recognized as an autoimmune disease and genes were pinpointed.
First Century AD Greek physician who identified celiac disease.
MORE INFORMATION
National nonprofit dedicated to accelerating diagnosis, treatments, and a cure for celiac disease.
RESEARCH
Development and validation of a high throughput next generation sequencing assay from buccal cell DNA as a cost-effective screening method for celiac genetic risk.
Shelly Gunn, Ambica Bhandari, Suman Verma, Harneet Gandhi, Dre’shon Rolle, Lony Lim, Philip Cotter, Mathew Moore.
Gluten ID presented at 2021 Association for Molecular Pathology meeting.
To download the poster please click here.
An estimated 1% of the global population has been diagnosed with celiac disease (CD), an autoimmune condition triggered by dietary gluten in individuals who carry HLA-DQ2 and/or HLA-DQ8 (DQ2/DQ8) celiac risk alleles. Clinical diagnosis of active CD is based on symptoms, serologic tissue transglutaminase (tTG) antibody testing, and characteristic histopathologic changes identified by small intestinal tissue biopsy. The presence of DQ2/DQ8 genes is necessary but not sufficient for development of CD, and the negative predictive value (NPV) of negative DQ2/DQ8 test results is > 90%. Approximately 30-40% of the general population carries specific allelic combinations for DQ2/DQ8 that would place them on a spectrum of risk for CD. However, despite the high NPV of DQ2/DQ8 testing, routine screening of celiac family members and asymptomatic individuals has traditionally been performed by tTG serologic testing and/or small intestinal biopsy. Disadvantages to this approach include false negative results in individuals who are not consuming dietary gluten, and unnecessary healthcare costs associated with repeated testing of asymptomatic individuals. In the current study we developed and validated a low cost, non-invasive, buccal cell DNA-based next generation sequencing (NGS) population screening method for the DQ2/DQ8 alleles.
Buccal cell DNA was collected from 98 healthy individuals (including multi-generation family members) and analyzed using next generation sequencing (NGS) technology to amplify and sequence across HLA-tagging celiac risk SNPs for DQ2.5, DQ8, DQ2.2, and DQ7 at a minimum of 40X coverage. Sequencing data was analyzed in Galaxy, where the fastq files were aligned, variants called, and SNP’s identified.
All possible heterozygous and homozygous combinations of celiac risk alleles were identified in the study population including non-celiac genetics (NCG), DQ2(cis), DQ2(trans) DQ8, and DQ7. Allelic inheritance could be clearly traced through multiple generations of families. A subset of 20 samples with known DQ2/DQ8 status performed by an outside CAP/CLIA certified clinical laboratory was used for qualitative analytical validation of the assay which showed 100% concordance with known DQ2/DQ8 results.
DQ2/DQ8 typing by NGS is a cost-effective screening method for celiac genetic risk in individuals, families, and populations. The assay identifies those with high-risk genetics who would benefit from annual serologic and/or small biopsy testing while allowing NCG low risk, asymptomatic individuals to forgo further screening for celiac disease.
