Expressive

rs12261843 (CCNY): Ulcerative Colitis Risk Locus

Key takeaways

  • The CCNY region at 10p11 is one of 47 confirmed ulcerative colitis risk loci, supported by a meta-analysis of more than 48,000 participants.
  • The alternate allele increases expression of CCNY-AS1, a long non-coding RNA, across six tissue types including lung, skeletal muscle, and prostate.
  • In immune cells, the same allele reduces expression of CREM, a gene involved in cellular signaling.
  • CCNY (cyclin Y) is the single consistently nominated candidate gene at this locus across multiple independent genomic annotation methods.

Key takeaways

  • The 10p11 chromosomal region, where CCNY (cyclin Y) sits, is one of 47 confirmed ulcerative colitis risk loci, supported by a meta-analysis covering more than 48,000 participants.
  • The alternate allele of this variant increases expression of CCNY-AS1, a long non-coding RNA (an RNA molecule that does not encode a protein), across six tissue types including lung, skeletal muscle, and prostate.
  • In immune cells, the same allele reduces expression of CREM, a gene involved in cellular signaling.
  • CCNY is the single candidate gene consistently nominated at this locus across multiple independent genomic annotation methods.

What the research says A meta-analysis of six ulcerative colitis (UC) genome-wide association studies identified the 10p11 region as one of 29 newly confirmed UC risk loci, bringing the confirmed total to 47; the discovery phase covered 6,687 UC cases and 19,718 controls of European descent, with validation in 9,628 additional cases and 12,917 controls. CCNY (cyclin Y, a protein that helps regulate the cell cycle) at this locus was one of only six loci in the entire genome-wide scan where a single candidate gene was consistently nominated across multiple independent annotation approaches, including literature mining with GRAIL, eQTL correlation, linkage with non-synonymous variants, and gene proximity analysis. The 47 confirmed UC loci identified in this work overlap with a broader set of 99 confirmed inflammatory bowel disease (IBD) risk loci, including at least 28 signals shared between UC and Crohn's disease.

Reported associations

  • Ulcerative colitis: The 10p11 locus reached genome-wide significance (P<5x10-8) in a European-ancestry discovery and replication cohort totaling over 48,000 participants, with CCNY flagged as the single prioritized candidate gene. No per-allele odds ratio for rs12261843 specifically is reported in the available study text.

Evidence quality The UC association at this locus was established at genome-wide significance (P<5x10-8) in a combined discovery and replication dataset exceeding 48,000 individuals, which is well-powered by GWAS standards. The nomination of a single unambiguous candidate gene at 10p11 is a relatively strong annotation outcome, given that 35 of the 47 confirmed UC loci harbor multiple genes and do not resolve to one clear candidate. No per-allele odds ratio or confidence interval for rs12261843 is available in the provided text, which limits quantification of per-allele effect. All participants were of European descent, which may limit generalizability to other populations. No functional validation studies linking CCNY biology to UC pathogenesis are described in the available materials, so the locus-trait relationship remains at the population-level statistical stage. No conflicting findings are reported across the studies provided.

Tissue-specific expression effects

  • CCNY-AS1: The alternate allele is associated with increased expression of this long non-coding RNA in prostate, skeletal muscle, tibial artery, breast mammary tissue, lung, and subcutaneous adipose tissue. GTEx Portal
  • CREM: The alternate allele is associated with reduced expression of CREM (cyclic AMP-responsive element modulator, a regulator of cellular signaling pathways) in EBV-transformed lymphocytes (a type of immune cell used in genetic research). GTEx Portal
  • ENSG00000230534: The alternate allele is associated with increased expression of this gene (not further characterized in the available data) in EBV-transformed lymphocytes. GTEx Portal

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is the CCNY gene and why is it a candidate here?

CCNY encodes cyclin Y, a protein involved in regulating the cell cycle (the process by which cells grow and divide). It was nominated as the single candidate gene at the 10p11 ulcerative colitis risk locus because multiple independent annotation methods, including literature mining and gene-expression analysis, all pointed to CCNY rather than other nearby genes.

What is ulcerative colitis?

Ulcerative colitis is a chronic inflammatory disease that affects the inner lining of the colon, classified as a form of inflammatory bowel disease (IBD). Genetic research has identified at least 47 confirmed susceptibility regions for UC, though the genetic factors found so far explain only a fraction of the disease's overall heritability.

Is rs12261843 also linked to Crohn's disease?

The study that identified this locus focused on ulcerative colitis. The same research noted 99 total confirmed IBD risk loci overall, including 28 regions shared between UC and Crohn's disease, but rs12261843 at 10p11 is listed specifically as a UC association in the available data. No Crohn's disease data for this variant are provided in the available sources.

What does it mean that this variant changes CCNY-AS1 expression in multiple tissues?

GTEx tissue data show the alternate allele is associated with higher levels of CCNY-AS1, a long non-coding RNA, in prostate, skeletal muscle, lung, and three other tissue types. This points to a potential molecular mechanism linking the variant to gene regulation, though expression changes in peripheral tissues do not on their own confirm a role in gut inflammation.

How large was the study that identified this UC risk locus?

The discovery meta-analysis combined six UC genome-wide association datasets covering 6,687 cases and 19,718 controls, all of European descent. Significant findings were replicated in an independent cohort of 9,628 cases and 12,917 controls, giving a total of over 48,000 participants across both stages.