Gluten immunogenomics

Celiac Disease
& Genetics

One of the few autoimmune diseases with near-deterministic genetics: no HLA-DQ2 or DQ8, no celiac disease.

helixXY precisely identifies your HLA-DQ2.5, DQ2.2 and DQ8 haplotypes — along with 4 additional non-HLA loci (IL2-IL21, CCR3, SH2B3, TAGAP) that modulate risk in positive carriers.

Analyze my DNA View analyzed genes

~99%

Negative predictive value

10–15×

Family risk

~1%

Global prevalence

Golden wheat field — Celiac Disease & Genetics

6 key genes

HLA-DQ2, DQ8 & more

Definitive rule-out

Only test with ~99% NPV

Genetics that rules out

A test that can
end doubts for good

Celiac Disease is an autoimmune enteropathy triggered by gluten ingestion (in wheat, barley, and rye) in genetically susceptible individuals. The result is destruction of intestinal villi, malabsorption of nutrients, and a cascade of clinical manifestations — diarrhea, anemia, osteoporosis, infertility, neurological symptoms.

The peculiarity of CD is that genetic susceptibility is virtually mandatory: HLA-DQ2 and HLA-DQ8 haplotypes are present in ~99% of patients. This makes the genetic test the exam with the highest negative predictive value in all of internal medicine — those without DQ2 or DQ8 can rule out the disease with nearly absolute confidence.

helixXY precisely identifies your haplotypes and integrates 4 additional non-HLA loci that help stratify the actual risk in positive carriers.

NPV near 100%

Absence of DQ2 and DQ8 rules out CD with ~99% confidence. In families with a history, this means an end to uncertainty for children who didn't inherit the haplotypes.

Necessary, but not sufficient

Having DQ2/DQ8 doesn't mean having CD. ~30% of the population has the haplotype, but only ~1% develops the disease. Non-HLA loci, microbiota, and environmental factors determine who progresses.

Use your existing data

Use your file from 23andMe, Genera, AncestryDNA, etc. Within 15 minutes of upload, your report is ready — no new sample required.

Analyzed genes

The 2 HLA haplotypes + 4 non-HLA loci
with the largest effect

Complete coverage of HLA-DQ2 and DQ8 haplotypes — disease-defining — alongside the main non-HLA risk modulators.

HLA-DQ2.5

Chromosome 6p21.32

The HLA-DQ2.5 haplotype (DQA1*05:01-DQB1*02:01) is the primary genetic determinant of Celiac Disease. Present in ~30% of the general population but ~95% of celiac patients. It presents gliadin-derived peptides (deamidated by tissue transglutaminase, TTG) to CD4+ T lymphocytes, triggering the autoimmune response.

Variants / alleles: DQA1*05:01DQB1*02:01DR3-DQ2 haplotype

~95%

of CD cases

HLA-DQ8

Chromosome 6p21.32

The HLA-DQ8 haplotype (DQA1*03:01-DQB1*03:02) is the second most important locus. Present in ~5% of pure cases and ~6% of DQ2-negative cases. When DQ8 is present without DQ2, risk is lower than with DQ2.5, but disease can still manifest — hence the importance of testing both.

Variants / alleles: DQA1*03:01DQB1*03:02DR4-DQ8 haplotype

~5%

of CD cases

IL2-IL21

Chromosome 4q27

Region 4q27 containing the IL2 and IL21 genes — central T-helper response cytokines. The strongest non-HLA locus for Celiac Disease. Variants in this region amplify inflammatory signaling after gluten exposure in DQ2/DQ8 carriers.

Variants / alleles: rs6822844rs6840978rs13119723

1.30×

odds ratio

CCR3 / CCR2

Chromosome 3p21.31

Chemokine receptors involved in eosinophil and monocyte migration to the intestinal mucosa. The 3p21.31 region contains multiple chemokine genes (CCR1, CCR2, CCR3, CCR5) whose variants modulate the inflammatory infiltration characteristic of celiac villous atrophy.

Variants / alleles: rs6441961rs13098911rs13314993

1.22×

odds ratio

SH2B3

Chromosome 12q24.12

SH2B Adaptor Protein 3 (LNK) — negative regulator of cytokine and growth factor signaling. The R262W variant (rs3184504) is shared with several autoimmune diseases (T1D, rheumatoid arthritis). Acts on the balance between tolerance and immune activation in the intestinal mucosa.

Variants / alleles: R262W (rs3184504)rs653178rs17696736

1.20×

odds ratio

TAGAP

Chromosome 6q25.3

T-Cell Activation Rho GTPase Activating Protein — regulates effector T lymphocyte activation and migration. TAGAP variants influence T-CD4 response to gluten peptides in HLA-risk carriers. Locus shared with Crohn's and rheumatoid arthritis.

Variants / alleles: rs1738074rs212389rs1393347

1.18×

odds ratio

Additional loci also analyzed: The report also includes HLA-DQ2.2 (DQA1*02:01-DQB1*02:02, intermediate risk) and variants in IL18RAP, RGS1, PTPN2, ICOSLG, CTLA4 and more than 30 other smaller-effect loci identified in international GWAS meta-analyses.

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Clarity on your plate

Not a trend diet
a DNA-based decision

Many people cut gluten "just in case" — losing nutrients, paying more, with no proven benefit. For the 99% without DQ2/DQ8, Celiac Disease is ruled out. Eat wheat, barley, and rye without fear.

For the ~1% with confirmed disease, strict gluten-free diet is healing: villous regeneration, end of malabsorption, reduced risk of intestinal lymphoma and other autoimmunities.

How it works

What helixXY delivers

An interpreted, contextualized, and actionable report — not just a list of variants.

Precise HLA typing

Unambiguous identification of HLA-DQ2.5, DQ2.2 and DQ8 haplotypes — the genetic definers of Celiac Disease, with clinical sensitivity and specificity.

Rule out with confidence

If DQ2 and DQ8 are negative, the report states the ~99% negative predictive value — useful to end repeat investigations in families with a history.

Stratification for positives

For DQ2/DQ8 carriers, we integrate 4 non-HLA loci (IL2-IL21, CCR3, SH2B3, TAGAP) into a score that estimates actual risk of clinical progression.

Guidance for next steps

Clear recommendations: when to order serology (anti-tTG IgA), when to indicate biopsy, and when to dispense with future investigations.

Continuous updates

As new loci and guidelines are published (ESPGHAN, NASPGHAN, ACG), your report is automatically revised — at no additional cost.

Absolute privacy

Your data is processed with AES-256 encryption in a zero-knowledge architecture. Full GDPR compliance.

Signs that warrant attention

Clinical presentation is heterogeneous — classic (digestive), atypical (extra-intestinal), or silent. In DQ2/DQ8 carriers, attention to subtle signs is essential.

Chronic diarrhea + weight loss

The classic presentation: voluminous diarrhea, steatorrhea (fatty stools), abdominal distension, and weight loss from malabsorption.

Refractory iron-deficiency anemia

Anemia from iron malabsorption that doesn't respond to oral replacement. CD is an important cause in young adults, especially women.

Recurrent oral ulcers

Frequent aphthous ulcers (>3 episodes/year) can be an extraintestinal manifestation of Celiac Disease.

Early osteopenia/osteoporosis

Malabsorption of calcium and vitamin D leads to accelerated bone loss. CD should be investigated in unexpectedly low BMD.

Infertility / recurrent miscarriages

Untreated CD is associated with infertility, recurrent miscarriages, and preterm delivery — reversible with a gluten-free diet.

Neurological symptoms

Headache, peripheral neuropathy, ataxia, anxiety, or depression without apparent cause — well-described neurological presentations of CD.

Frequently asked questions

Clear, evidence-based answers about genetics and Celiac Disease.

If I don't have HLA-DQ2 or DQ8, can I rule out Celiac Disease?

I have DQ2/DQ8 but no symptoms. Do I have the disease?

Can I start a gluten-free diet before definitive diagnosis?

Is Celiac Disease the same as non-celiac gluten sensitivity?

Are my children at increased risk?

Celiac Disease
& Genetics