rs11167764 (NDFIP1): Crohn's Disease Risk Variant

Key takeaways

• rs11167764 is one of 71 confirmed genetic loci linked to Crohn's disease risk, discovered through a large international meta-analysis.
• The NDFIP1 gene at this locus is notable: the associated region contains only one gene, making NDFIP1 the most direct candidate rather than one of several possibilities.
• The finding is backed by data from over 50,000 individuals across multiple independent populations, with no significant differences in effect size between countries.
• GTEx data shows this variant is associated with increased NDFIP1 expression in skeletal muscle and altered expression of nearby genes across several other tissues.

What the research says A meta-analysis combining six Crohn's disease (CD) genome-wide association studies (GWAS), large surveys of genetic variants across thousands of people, identified rs11167764 within the GNPDA1-NDFIP1 locus as one of 30 new genome-wide significant CD susceptibility loci. The discovery panel included 6,333 CD cases and 15,056 European-descent controls, with findings replicated in an independent panel of 15,694 cases, 14,026 controls, and 414 parent-offspring trios. Among the 71 total confirmed loci, NDFIP1 stands out because its associated region contains just a single gene, making it one of the more directly interpretable signals in the entire CD genetic landscape.

Reported associations

• Crohn's disease susceptibility: rs11167764 reached genome-wide significance (P < 5x10^-8) in a meta-analysis of six GWAS datasets (6,333 cases, 15,056 controls at discovery), with replication in 15,694 additional cases and 14,026 controls; no statistically significant heterogeneity of effect sizes was observed across the 15 contributing countries.

Evidence quality The association at this locus meets genome-wide significance (P < 5x10^-8), a threshold designed to control for the large number of genetic variants tested simultaneously across the human genome. Data were pooled from six independent GWAS studies of European-descent populations and followed up in a large independent replication cohort, including 414 parent-offspring trios. The meta-analysis had 80% statistical power to detect variants with odds ratios of 1.18 or greater at minor allele frequencies above 20%; no specific odds ratio for rs11167764 is provided in the available study text. The 71 confirmed CD loci collectively explained only approximately 20% of the genetic contribution to disease risk, indicating that many additional variants remain to be identified. No significant effect-size heterogeneity was detected across the 15 contributing countries.

Tissue-specific expression effects

• NDFIP1: The alternate allele is associated with increased expression in skeletal muscle GTEx Portal.
• ENSG00000300089: The alternate allele is associated with reduced expression in testis GTEx Portal.
• ENSG00000289306: The alternate allele is associated with increased expression across multiple tissues including subcutaneous adipose tissue, tibial nerve, lower-leg skin, skeletal muscle, tibial artery, and thyroid GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.