Expressive

rs12242110 (CCNY-AS1): Crohn's Disease Risk Locus

Key takeaways

  • rs12242110 at the CCNY-AS1 locus is one of 71 confirmed genetic risk variants for Crohn's disease found in a large international study
  • The discovery spanned 6,333 cases and 15,056 controls, replicated in over 29,000 more individuals from 15 countries
  • The alternate allele increases CCNY-AS1 expression in tibial artery, skeletal muscle, lung, and other tissues
  • The same allele reduces CREM expression in EBV-transformed lymphocytes (immune cells)

Key takeaways

  • rs12242110, at the CCNY-AS1 locus, is one of 71 confirmed genetic risk variants for Crohn's disease identified in a large international genome-wide study
  • The discovery phase covered 6,333 Crohn's disease cases and 15,056 controls, with replication in 15,694 additional cases and 14,026 controls across 15 countries
  • The alternate allele is associated with increased CCNY-AS1 expression in tibial artery, skeletal muscle, lung, and other tissues
  • The same allele is linked to reduced CREM expression in EBV-transformed lymphocytes (immune cells)

What the research says A meta-analysis of six Crohn's disease (CD) genome-wide association studies (GWAS - a study design that tests genetic variants across the entire genome to find disease-linked differences) identified rs12242110 at the CCNY-AS1 locus as one of 71 confirmed CD susceptibility loci meeting genome-wide significance (P < 5 x 10^-8). The discovery panel included 6,333 CD cases and 15,056 controls of European descent, followed by replication in 15,694 cases, 14,026 controls, and 414 parent-offspring trios across 15 countries. The study was designed with 80% statistical power to detect variants with an odds ratio (OR, a measure comparing disease risk between allele carriers and non-carriers) of at least 1.18, assuming a minor allele frequency of 20% or greater.

Reported associations

  • Crohn's disease: rs12242110 is among 71 genome-wide significant (P < 5 x 10^-8) CD susceptibility loci confirmed in a major GWAS meta-analysis. No specific OR for this variant is reported in the available study text; the study's power threshold was an OR of at least 1.18 at a minor allele frequency of 20%.

Evidence quality Evidence rests on a large, multi-national meta-analysis of six cohorts with a structured discovery-plus-replication design. No statistically significant heterogeneity of odds ratios was observed across the 15 contributing countries (Breslow-Day test after Bonferroni correction), indicating consistent effects within European-ancestry populations. All participants were of European descent, which limits direct generalizability to other ancestries. The specific OR for rs12242110 is not available in the provided study text, and no conflicting findings are reported in the available evidence.

Tissue-specific expression effects

  • CCNY-AS1: The alternate allele is associated with increased expression in tibial artery, skeletal muscle, cultured fibroblasts, lung, and thyroid GTEx Portal
  • CREM: The alternate allele is associated with reduced expression in EBV-transformed lymphocytes (immune cells) GTEx Portal
  • ENSG00000230534: The alternate allele is associated with increased expression in EBV-transformed lymphocytes GTEx Portal
  • LINC02635: The alternate allele is associated with reduced expression in stomach tissue GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

Is rs12242110 linked to Crohn's disease?

Yes. A meta-analysis of six genome-wide association studies identified rs12242110 as one of 71 variants meeting the genome-wide significance threshold for association with Crohn's disease, across more than 50,000 individuals from 15 countries.

What is the CCNY-AS1 gene?

CCNY-AS1 is the gene at the rs12242110 locus. GTEx expression data show that the alternate allele is associated with higher CCNY-AS1 expression in tibial artery, skeletal muscle, cultured fibroblasts, lung, and thyroid.

What tissues does rs12242110 affect gene expression in?

GTEx data show the alternate allele increases CCNY-AS1 expression in tibial artery, skeletal muscle, cultured fibroblasts, lung, and thyroid. It also reduces CREM expression in immune cells and reduces LINC02635 expression in stomach tissue.

What is Crohn's disease?

Crohn's disease is a form of inflammatory bowel disease (IBD) caused by the interaction of environmental factors, the gut microbiome, and host immune responses in genetically susceptible individuals. rs12242110 is one of 71 genetic variants associated with this condition.

How reliable is the evidence for rs12242110 and Crohn's disease?

The association reached genome-wide significance (P < 5 x 10^-8) in a large multi-national meta-analysis with no significant heterogeneity across 15 contributing countries. Evidence is based entirely on individuals of European descent, so applicability to other ancestries is not established.