rs9273363
badMag 6.5This is a intergenic variant variant in the HLA-DQB1 gene.
Key Literature Trait Associations
Type 1 Diabetes
The A allele at rs9273363 tags the high-risk HLA class II haplotypes HLA-DRB1*04:01-DQA1*03:01-DQB1*03:02 and HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01, which present islet autoantigens to CD4+ T cells and drive autoimmune beta-cell destruction. This SNP is the strongest common genetic predictor of type 1 diabetes, and together with two other tag SNPs can identify high-risk HLA-DR/DQ genotypes with over 99% accuracy. Homozygous AA carriers have substantially elevated risk.
Chronic lymphocytic leukemia
The A allele of rs9273363 was associated with elevated risk of B-cell chronic lymphocytic leukemia (CLL) with OR=1.24 per copy at p=2×10⁻¹⁰ in a multi-cohort GWAS meta-analysis (Berndt et al., Nat Genet 2013). The study enrolled 3,100 CLL cases and 7,667 controls of European ancestry from over 15 countries. The biological rationale is plausible given the SNP's MHC class II location: HLA-DQ variation influences antigen presentation to B cells, potentially modulating B-cell proliferative responses. The effect size is modest (OR ~1.24) but achieved genome-wide significance with replication.
CD74/IL18BP protein ratio
rs9273363 is a highly significant protein quantitative trait locus (pQTL) for the ratio of CD74 to IL18BP plasma levels. In the UK Biobank pQTL study by Suhre et al. (Cell Genomics, 2024; n=43,509), this variant showed an extreme association (beta=0.215, p=2×10⁻¹⁸³) with the CD74/IL18BP ratio. CD74 is an MHC class II chaperone protein and IL18BP is an anti-inflammatory interleukin-18 binding protein; both are functionally relevant to immune regulation and autoimmunity, consistent with this SNP's HLA-DQB1 proximity.
▶GWAS Catalog Trait Associations (5)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (5)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
type 1 diabetes mellitus
diabetic ketoacidosis
fatty acid amount
diabetes mellitus, Drugs used in diabetes use measurement
chronic lymphocytic leukemia
▶Research that mentions this SNP (2)
▶The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of ageAssociationN=35,206Jamie R. J. Inshaw et al.(2018)· Diabetologia
This genome-wide association study identified two regions associated with age at diagnosis (AAD) of type 1 diabetes using ImmunoChip data from 15,696 cases: the MHC region (lead SNP rs9273363, p=2.16×10⁻³⁵) and the 6q22.33 region (lead SNP rs72975913, p=2.94×10⁻¹⁰, near PTPRK and THEMIS genes). The 6q22.33 region showed stronger association with early-onset type 1 diabetes (diagnosed <5 years, OR=0.78 for rs72975913), with a combined effect of 4.12 years younger diagnosis in homozygous carriers of both risk alleles.
▶RET Gly691Ser mutation is associated with primary vesicoureteral reflux in the French-Canadian population from QuebecMethodsN=17,000Yaoming Yang et al.(2008)· Human Mutation
iLOCi is a novel SNP interaction prioritization algorithm designed to detect gene-gene interactions (epistasis) in genome-wide association studies by accounting for marker dependencies separately in case and control groups. Validated on WTCCC data across seven complex diseases (bipolar disorder, coronary artery disease, Crohn's disease, hypertension, rheumatoid arthritis, type 1 diabetes, and type 2 diabetes), the algorithm identified disease-associated SNP pairs including hub SNPs such as rs1553460 for bipolar disorder and rs3785579 for coronary artery disease and rheumatoid arthritis, revealing both previously known disease genes (TCF7L2 for T2D, HLADQB1 for T1D) and novel disease-associated genes (CACNG1 for rheumatoid arthritis).
Gene information from NCBI Gene. Variant classifications from ClinVar.
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