Gut immunogenomics

Crohn's Disease
& Genetics

Chronic inflammatory bowel disease with strong heritability. NOD2, ATG16L1 and IL23R are pillars of genetic risk.

helixXY analyzes the main susceptibility loci — including variants in bacterial recognition (NOD2), autophagy (ATG16L1, IRGM) and the Th17/IL-23 pathway — providing a map of your risk and context for clinical discussions.

Analyze my DNA View analyzed genes

8–10×

Family risk

~240

Known loci

15–35

Peak age

Gut microbiome illustration — Crohn's Disease & Genetics

6 key genes

NOD2, IL23R & more

Microbiome + DNA

Gut-immune axis

Where genetics meets the gut

When the gut barrier
stops filtering well

Crohn's Disease is a chronic, transmural inflammation that can affect any segment of the gastrointestinal tract — from mouth to anus, most often the terminal ileum. The current model describes a dysregulated immune response to the microbiota in a genetically predisposed host.

The implicated genes converge on three major pathways: bacterial recognition (NOD2), autophagy (ATG16L1, IRGM), and Th17 adaptive immunity (IL23R). When these pathways fail, Paneth cells and macrophages lose control over the microbiota, and inflammation becomes self-sustaining.

helixXY maps variants at the main loci, contextualizing the genetic risk and providing inputs for an informed conversation with your gastroenterologist.

NOD2 is the anchor gene

The three main variants (R702W, G908R, 1007fs) raise risk 3–4× (heterozygotes) and up to 20–40× (homozygotes), and are also associated with ileal and stricturing phenotypes.

Genetics guided new therapies

The discovery of the IL-23 pathway from the IL23R gene led to the development of ustekinumab and risankizumab — biologics that today change the course of the disease.

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 6 highest-impact loci
of susceptibility

helixXY analyzes the best-characterized loci from International IBD Genetics Consortium (IIBDGC) meta-analyses.

NOD2 (CARD15)

Chromosome 16q12.1

The first susceptibility gene identified for Crohn's Disease (2001). NOD2 is an intracellular sensor of bacterial muramyl dipeptide. The three main variants (R702W, G908R, 1007fs) impair recognition of the microbiota and lead to uncontrolled inflammatory response — homozygotes have 20–40× elevated risk.

Common variants: R702W (rs2066844)G908R (rs2066845)1007fs (rs2066847)

3–4×

odds ratio (heterozygous)

ATG16L1

Chromosome 2q37.1

Essential component of the autophagy complex, responsible for clearing intracellular pathogens and regulating inflammation. The T300A variant (rs2241880) compromises autophagy in Paneth cells of the ileum, creating the cellular substrate for Crohn's Disease.

Common variants: T300A (rs2241880)rs10210302rs6431654

1.5×

odds ratio

IL23R

Chromosome 1p31.3

Interleukin-23 receptor, central to the Th17 pathway of adaptive immunity. Notably, the R381Q variant (rs11209026) is PROTECTIVE — it reduces Crohn's risk by 60–70%. Inspired the development of anti-IL-23 therapies (ustekinumab, risankizumab) now approved for the disease.

Common variants: R381Q (rs11209026, protective)rs1004819rs7517847

0.4×

(protective variant)

IRGM

Chromosome 5q33.1

Immunity-related GTPase, complementary to ATG16L1 in the autophagic control of intracellular bacteria. IRGM variants alter expression in intestinal epithelial cells, compromising the barrier against the microbiota.

Common variants: rs13361189rs10065172rs4958847

1.4×

odds ratio

TNFSF15

Chromosome 9q32

TNF superfamily member, ligand of the DR3 receptor. TNFSF15 variants increase TNF-mediated inflammatory signaling. Particularly relevant in Asian populations, where NOD2 plays a smaller role — exemplifies the ethnic heterogeneity of genetic risk.

Common variants: rs7848647rs4263839rs6478108

1.4×

odds ratio

PTPN22

Chromosome 1p13.2

Curiously, the R620W variant in PTPN22 — which increases risk for several autoimmune diseases (T1D, rheumatoid arthritis, lupus) — has a PROTECTIVE effect against Crohn's Disease. Demonstrates the complexity of the balance between adaptive and innate immunity in CD pathophysiology.

Common variants: R620W (rs2476601, protective)rs33996649rs1217414

0.8×

(protective variant)

Additional loci also analyzed: The complete report also includes variants in STAT3, JAK2, CARD9, SMAD3, ZNF365, NKX2-3 and 200+ other smaller-effect loci identified in GWAS meta-analyses.

Photo by Luis Miguel P. Bonilla on Pexels

Living well with genetic risk

Knowing means
acting early

Knowing your genetic predisposition allows heightened attention to early symptoms — and opens space for informed lifestyle decisions: quitting smoking (the largest modifiable environmental factor for Crohn's), reducing ultra-processed foods, and caring for sleep and stress.

It's not about anxious surveillance. It's about turning data into conscious choices — alongside your gastroenterologist.

How it works

What helixXY delivers

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

Key-pathway analysis

Variants in bacterial recognition (NOD2), autophagy (ATG16L1, IRGM), and the Th17/IL-23 pathway (IL23R) are analyzed and contextualized.

CD polygenic risk score

We combine dozens of loci into a Crohn's Disease Polygenic Risk Score validated in IIBDGC and UK Biobank cohorts of 75,000+ cases.

Clear clinical context

Each finding comes with literature reference, absolute and relative risk percentages, and context on specific phenotypes (ileal, fistulizing, stricturing).

Pharmacogenomic insights

Variants in IL23R and TPMT/NUDT15 can inform discussions on anti-IL-23 biologic efficacy and thiopurine safety.

Continuous updates

As new loci are discovered and guidelines updated, 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

Crohn's Disease can evolve slowly. In carriers of high genetic risk, increased attention to persistent symptoms is essential.

Chronic diarrhea

Persistent diarrhea for more than 4 weeks, with or without blood. May include mucus and bowel urgency.

Abdominal pain

Cramping pain, usually in the right lower quadrant (terminal ileum). Often worsens after meals.

Weight loss

Unintentional weight loss from malabsorption and chronic inflammation. May cause growth delay in children.

Persistent fatigue

Disproportionate tiredness, often associated with iron-deficiency anemia from bleeding or malabsorption.

Anal fissures / fistulas

Perianal lesions (fissures, fistulas, abscesses) are a hallmark of Crohn's — affecting ~30% of patients.

Extraintestinal manifestations

Large-joint arthritis, uveitis, erythema nodosum, recurrent oral aphthae — may precede intestinal symptoms.

Frequently asked questions

Clear, evidence-based answers about genetics and Crohn's Disease.

I have a relative with Crohn's Disease. Does my risk increase?

Do NOD2 variants mean I will develop Crohn's?

Does genetics influence which treatment works best?

Do Crohn's and Ulcerative Colitis share the same genetic basis?

What symptoms should I watch for?

Crohn's Disease
& Genetics