Crohn’s disease shares genetic roots with a kidney disorder, large study finds

If you live with Crohn's disease and have ever wondered whether your gut trouble could quietly be putting other organs at risk, a new genetics study gives that suspicion some real weight. Researchers combined genome-wide genetic data with a clinical cohort of over 9,000 patients and found that Crohn's disease, specifically, shares genetic architecture with IgA nephropathy (a common kidney disease caused by antibody deposits damaging the kidney's filtering units), and that having Crohn's raises the genetic odds of developing it. Ulcerative colitis, the other major form of inflammatory bowel disease, showed no such link.

Key takeaways:

• Crohn's disease shares a meaningful chunk of its genetic architecture with IgA nephropathy (genetic correlation up to 0.392), while ulcerative colitis does not.
• Genetic liability to Crohn's disease was associated with roughly a 7% higher relative risk of IgA nephropathy in both European and East Asian populations.
• In a real-world hospital cohort of 9,371 IBD patients, biopsy-confirmed IgA nephropathy was over 3 times more common in Crohn's patients than in ulcerative colitis patients.
• Two genes, ERAP2 and CARD9, stood out as likely molecular links, pointing to the immune system rather than the kidney itself as the shared trigger.

Crohn's Disease Genetically Linked to IgA Nephropathy

Crohn's disease shows a consistent, positive genetic link to IgA nephropathy (IgAN) risk, according to a study published in Frontiers in Immunology. The research team, based at the Sixth Affiliated Hospital of Sun Yat-sen University in China, used genome-wide association study (GWAS) data (large public datasets that scan the genome for variants linked to a disease) from both European and East Asian populations to test whether inflammatory bowel disease (IBD) and IgAN, one of the most common kidney diseases worldwide, share a genetic basis. Using a technique called Mendelian randomization (MR), which uses genetic variants as natural experiments to test cause-and-effect relationships, they found that genetic liability to Crohn's disease raised the odds of IgAN by about 7% in Europeans (odds ratio 1.068) and by a similar amount in East Asians (odds ratio 1.071). Ulcerative colitis (UC), the other main IBD subtype, showed no such signal in either population, pointing to something specific about Crohn's biology rather than intestinal inflammation in general.

Beyond that directional signal, a separate genome-wide method called linkage disequilibrium score regression (LDSC), which measures how much two conditions' genetic risk factors overlap across the entire genome, found a genetic correlation of 0.392 between Crohn's disease and IgAN, a magnitude the authors describe as comparable to other well-established immune-disease genetic overlaps. A second independent method, GNOVA, produced a consistent result. Ulcerative colitis, by contrast, only bordered on statistical significance (P = 0.062) for its genetic overlap with IgAN, reinforcing that this is a Crohn's-specific pattern.

Why IBD Patients Should Care About Kidney Risk

For the roughly 3 million people in the United States living with inflammatory bowel disease, this finding sharpens a distinction that matters: not all IBD carries the same downstream risk. IgA nephropathy often develops silently, sometimes showing up only as blood or protein in urine, and it can progress toward chronic kidney disease over years if untreated. A review of the gut-kidney axis in IBD notes that IgAN is already recognized as one of the more common kidney lesions seen in Crohn's disease specifically, and this new genetic evidence helps explain why: it's not simply that gut inflammation spills over into the kidneys, but that Crohn's and IgAN appear to share underlying immune biology at the genetic level. That distinction matters for a patient managing Crohn's, because it suggests kidney monitoring is a Crohn's-specific consideration rather than a generic IBD precaution.

How Researchers Tested 9,371 IBD Patients' Genes

The study's most concrete evidence came from a single-center retrospective cohort of 9,371 hospitalized IBD patients treated between October 2012 and October 2025, split into 7,149 with Crohn's disease and 2,222 with ulcerative colitis. Among Crohn's patients, biopsy-confirmed IgA nephropathy occurred in 38 of 7,149 patients (0.53%), compared with just 4 of 2,222 ulcerative colitis patients (0.18%). After adjusting for age and sex, Crohn's patients had 3.4 times the odds of biopsy-proven IgAN compared with ulcerative colitis patients (P = 0.0125). A broader measure, any biopsy-confirmed kidney disease, showed a similar pattern: Crohn's patients had roughly 2.6 times the adjusted odds compared with ulcerative colitis patients (P = 0.0016). To identify which genes might explain the link, the team also layered in colocalization analysis (a statistical test for whether two diseases are driven by the same underlying genetic variant) and single-cell RNA sequencing of immune cells. Two genes rose to the top: ERAP2, with the strongest support in colon tissue (90.4% posterior probability of a shared causal variant), and CARD9, with very strong support at the whole-genome level (98.4%). Notably, the genetic signal enriched in blood and spleen tissue, not kidney tissue, suggesting the disease connection runs through systemic immune programming rather than a kidney-specific process.

What This Means If You Have Crohn's Disease

If you have Crohn's disease, this study is a reason to ask your gastroenterologist or primary care doctor about routine urine testing (checking for blood or protein) as part of your regular monitoring, since IgAN is frequently caught this way before symptoms appear. It is not a reason to assume you will develop kidney disease. The absolute numbers in the clinical cohort were small: just over half a percent of Crohn's patients had biopsy-confirmed IgAN. What has changed is the confidence that this link is biologically real, not just a byproduct of how doctors happen to test IBD patients, or older observational research alone. It is also worth noting that a targeted-release form of budesonide, a steroid designed to act on immune tissue in the distal small intestine, has already received FDA approval as a treatment for IgA nephropathy itself, a detail the study authors cite as separate evidence that the gut and the kidney are mechanistically connected in this disease, though that approval was not based on Crohn's patients and this study does not test any treatment.

Limitations: What This Study Doesn't Prove

The strongest caveat is that this was ultimately a single-center, retrospective clinical cohort, meaning the 9,371-patient numbers come from one hospital's records rather than a randomized or multi-site study, which limits how confidently the findings generalize. The genetic data for IgA nephropathy was also comparatively sparse and drawn from fewer ancestral populations than the Crohn's disease datasets, which can weaken statistical power. And the study's own sensitivity analysis, using a method called CAUSE, did not clearly favor a causal model over one where Crohn's and IgAN simply share genetic risk factors without one directly causing the other. In plain terms: the genetic overlap is solid, but exactly how much of the Crohn's-to-IgAN relationship is direct causation versus shared underlying immune wiring remains an open question the authors are upfront about.

What Comes Next for Gut-Kidney Research

The authors frame their results as an early map, not a finished mechanism, of what they call a "gut-immune-kidney axis." The next step would be validating ERAP2 and CARD9's role with functional lab experiments rather than genetic association alone, and building larger, multi-center clinical cohorts, ideally with more diverse ancestries, to confirm the roughly threefold difference in kidney risk seen between Crohn's and ulcerative colitis patients. No timeline for that follow-up work was given in the study.

Common Questions

Does this mean Crohn's disease causes kidney disease? Not definitively. The study found a strong genetic and statistical association, and Mendelian randomization analyses lean toward Crohn's disease liability raising IgAN risk, but the authors' own sensitivity analysis could not clearly rule out that the two diseases simply share genetic risk factors rather than one directly causing the other.

Should I get my kidneys checked if I have Crohn's disease? This study suggests it is a reasonable question to raise with your doctor, particularly for routine urine testing, but it does not establish new screening guidelines, and the absolute risk in the study cohort was still low (about 0.53%).

Why does Crohn's disease show this link but ulcerative colitis doesn't? The researchers point to biological differences: Crohn's disease more often involves the small intestine, causes deeper (transmural) inflammation, and is associated with a higher rate of complications outside the gut, all of which may create more opportunity for immune dysregulation to extend beyond the intestine.

What are ERAP2 and CARD9? They are genes involved in immune function, ERAP2 in processing proteins for immune recognition and CARD9 in a signaling pathway linked to inflammation in immune cells called myeloid cells. The study found both genes show activity patterns consistent with a shared role in Crohn's disease and IgA nephropathy.

References

1. Tao Su, Mengjun Liang, Xiaohang Gao, et al. (2026). Shared genetic architecture between Crohn’s disease and IgA nephropathy: implications for a gut–immune–kidney axis. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2026.1905767
2. Roberto de Sire, Alessia La Mantia, Livio Bonacci, et al. (2024). Inflammatory Bowel Diseases and Nephropathies: Exploring the Gut–Kidney Axis. Life. https://doi.org/10.3390/life14121541