Expressive

rs11465802 (IL23R): Psoriasis and Autoimmune Risk

Key takeaways

  • This variant sits near two chromosome 1 genes: C1orf141 (a gene of incompletely characterized function) and IL23R (the interleukin-23 receptor), both implicated in immune signaling.
  • The locus has been linked to psoriasis risk in a multi-ancestry GWAS of 472,819 individuals, one of 74 genome-wide significant loci identified.
  • The same chromosomal region appears in cross-trait studies connecting rheumatoid arthritis genetically to IBD, multiple sclerosis, and type 1 diabetes.
  • GTEx expression data link this variant to reduced activity of IL12RB2 (an immune receptor subunit gene) specifically in skeletal muscle tissue.

Key takeaways

  • This variant sits near two chromosome 1 genes: C1orf141 (a gene of incompletely characterized function) and IL23R (the interleukin-23 receptor), both implicated in immune signaling.
  • The locus has been linked to psoriasis risk in a multi-ancestry GWAS of 472,819 individuals, one of 74 genome-wide significant loci identified.
  • The same chromosomal region appears in cross-trait studies connecting rheumatoid arthritis genetically to IBD, multiple sclerosis, and type 1 diabetes.
  • GTEx expression data link this variant to reduced activity of IL12RB2 (an immune receptor subunit gene) specifically in skeletal muscle tissue.

What the research says A multi-ancestry GWAS meta-analysis of psoriasis encompassing 28,869 cases and 443,950 controls identified 74 genome-wide significant loci, with common variants collectively accounting for roughly 15% of psoriasis heritability; psoriasis-risk loci showed positive genetic correlations with ulcerative colitis, IBD, and Crohn's disease. A separate cross-trait GWAS exploring genetic overlap among rheumatoid arthritis (RA), multiple sclerosis (MS), IBD, and type 1 diabetes (T1D) identified 86 shared loci for RA and IBD, 107 for RA and T1D, and 58 for RA and MS, with 82 common risk genes identified across those pairs. GTEx v11 data (953 donors) link rs11465802 to reduced IL12RB2 expression in skeletal muscle (slope -0.11, p=1.5e-4) GTEx Portal.

Reported associations

  • Psoriasis: The locus falls within one of 74 genome-wide significant psoriasis risk regions identified across 28,869 cases and 443,950 controls; common variants across all 74 loci jointly explain roughly 15% of psoriasis genetic risk.
  • Shared genetic risk for rheumatoid arthritis and inflammatory bowel disease: This region was among 86 independent shared loci identified in a cross-trait analysis of RA and IBD.
  • Shared genetic risk for rheumatoid arthritis and type 1 diabetes: This region was among 107 independent shared loci in a cross-trait analysis of RA and T1D.
  • Shared genetic risk for rheumatoid arthritis and multiple sclerosis: This region was among 58 independent shared loci in a cross-trait analysis of RA and MS.
  • IL12RB2 expression in skeletal muscle: The variant is associated with reduced IL12RB2 expression in skeletal muscle (slope -0.11, p=1.5e-4) GTEx Portal.

Evidence quality The psoriasis evidence derives from a large multi-ancestry meta-analysis (28,869 cases, 443,950 controls) that meets genome-wide significance (p < 5x10-8) and applied MR-MEGA, a method designed for multi-ancestry data. The RA cross-trait associations come from a large cross-trait GWAS that also applied Mendelian randomization, finding possible causal links between RA and MS and between RA and T1D, lending some causal support to the shared loci. However, neither study reports a per-SNP odds ratio for rs11465802 specifically, so individual-variant effect sizes for psoriasis and autoimmune associations are not available from these sources. The GTEx eQTL for IL12RB2 in skeletal muscle is FDR-corrected (953 donors), but the functional relevance of this tissue-specific expression change to clinical outcomes is not established from the available data. All associations should be treated as preliminary in the absence of replicated per-SNP effect estimates.

Tissue-specific expression effects

  • IL12RB2: The ALT allele is associated with reduced expression of IL12RB2 (a subunit of the interleukin-12 receptor, involved in immune signaling) in skeletal muscle, based on GTEx v11 data from 953 donors (slope -0.11, p=1.5e-4) GTEx Portal.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs11465802?

rs11465802 is a genetic variant located near two genes on chromosome 1: C1orf141 and IL23R, the interleukin-23 receptor. Large genome-wide studies have linked the region to psoriasis and to shared genetic risk across several autoimmune diseases.

Is rs11465802 linked to psoriasis?

A multi-ancestry genome-wide meta-analysis of 472,819 individuals identified the region containing rs11465802 as one of 74 genome-wide significant loci for psoriasis. The individual variant's odds ratio was not reported in the available studies.

Does this variant affect rheumatoid arthritis or other autoimmune diseases?

Cross-trait GWAS research found that the region near rs11465802 is among many shared loci linking rheumatoid arthritis with inflammatory bowel disease, type 1 diabetes, and multiple sclerosis, suggesting a shared immune-related genetic basis across these conditions.

What does IL23R do?

IL23R encodes the interleukin-23 receptor, a protein on immune cells that receives signals from interleukin-23, a molecule that helps regulate inflammation. Variants in and near this gene have been studied in connection with multiple immune-mediated diseases.

What is the connection between this variant and IL12RB2?

GTEx expression data show that rs11465802 is associated with reduced activity of IL12RB2, a gene encoding a subunit of the interleukin-12 receptor, in skeletal muscle tissue. The clinical significance of this tissue-specific effect is not yet established.