rs7454108

badMag 7.0

This is a intron variant variant in the HLA-DQB1 gene.

Key Literature Trait Associations

Type 1 Diabetes

rs7454108 tags the HLA-DR3/DQ2 and DR4/DQ8 haplotypes, the two strongest genetic risk factors for type 1 diabetes. These HLA class II molecules present beta-cell autoantigens (insulin, GAD65, IA-2) to CD4+ T cells, initiating the autoimmune destruction of pancreatic islets. Compound heterozygotes carrying both DR3/DQ2 and DR4/DQ8 (the DR3/4 genotype) face the highest T1D risk, with an OR of approximately 16 compared to the general population.

Barker JM et al. “Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening.” Diabetes (2008)

Allele C

OR —

p —

N 5,162

Preliminary work

European

Barrett JC et al. “Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.” Nature Genetics 41(6):703-707 (2009)

Allele C

OR 4.50

p 1.0e-200

Meta-analysis

Andersen MK et al. “Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study.” European Journal of Endocrinology (2012)

Allele C

OR 1.70

p 4.0e-4

N 2,764

Preliminary work

Danish/European

Eleftheriou A et al. “The High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Polymorphisms Are Differentially Associated With Growth and IGF-I Levels in Infancy: The Cambridge Baby Growth Study.” Diabetes Care (2021)

Allele C

OR —

p 3.0e-3

N 612

Preliminary work

European

Pemphigus vulgaris

rs7454108, located at the TAP2 gene within the MHC region, was identified as an independent risk variant for pemphigus vulgaris in a Han Chinese GWAS with discovery and replication cohorts totaling 492 cases and 2,883 controls. The C allele confers an odds ratio of 3.25 (p=2.78×10⁻¹²), independent of HLA-DRB1*14:04, the primary MHC risk allele for this disease. This finding suggests that TAP2-mediated antigen processing contributes independently to pemphigus vulgaris susceptibility beyond classical HLA-DRB1 associations.

Gao J et al. “Association Study and Fine-Mapping Major Histocompatibility Complex Analysis of Pemphigus Vulgaris in a Han Chinese Population.” The Journal of Investigative Dermatology 138(11):2307-2314 (2018)

Allele C

OR 3.25

p 2.8e-12

N 2,375

Large GWAS

Han Chinese

Celiac disease

rs7454108 tags the HLA-DQ8 haplotype (DQB1*03:02), one of the two major genetic prerequisites for celiac disease alongside HLA-DQ2. Virtually all celiac disease patients (>97%) carry HLA-DQ2 or HLA-DQ8, making this tagging SNP a powerful exclusion marker for celiac disease. The C allele at rs7454108 has been validated as a rapid, low-cost method for HLA-DQ8 haplotype detection applicable to saliva-based celiac screening, with the combined DQ2/DQ8 SNP panel achieving pooled sensitivity of 98% in meta-analyses of HLA typing studies.

Sebastian-delaCruz M et al. “A fast, cheap, and easy protocol for celiac disease HLA haplotype typing using buccal swabs.” Methods in Cell Biology (2023)

Allele C

OR —

p —

Candidate gene study

European

Díaz-Redondo A et al. “The potential usefulness of human leukocyte antigen typing for celiac disease screening: A systematic review and meta-analysis.” Revista Espanola De Enfermedades Digestivas (2015)

Allele C

OR —

p —

N 1,303

Meta-analysis

multi-ancestry

ANCA-associated vasculitis

rs7454108, in the HLA-DQ region of chromosome 6p21, is associated with ANCA-associated vasculitis (AAV) with OR=2.73 (p=5×10⁻²⁵) in GWAS data. The Lyons 2012 NEJM landmark GWAS of AAV found that anti-MPO ANCA was associated with HLA-DQ (p=2.1×10⁻⁸), consistent with rs7454108 as a DQ8 tag. HLA-DQ variants have been specifically linked to the myeloperoxidase-ANCA subtype of AAV rather than the proteinase 3-ANCA subtype, suggesting distinct immunological pathways underlie these clinically overlapping vasculitides.

Lyons PA et al. “Genetically distinct subsets within ANCA-associated vasculitis.” The New England Journal of Medicine (2012)

Allele C

OR —

p 2.1e-8

N 4,387

Large GWAS

European

Rheumatoid arthritis

rs7454108 was identified as an interaction locus for ACPA-positive rheumatoid arthritis in the context of smoking in the Swedish EIRA cohort. The OR of 1.72 (p=2×10⁻⁶) was observed after adjustment for HLA shared epitope, suggesting rs7454108 tags an HLA-DQ haplotype that interacts with tobacco exposure to modulate RA susceptibility. This association is conditional and did not reach the stringent genome-wide significance threshold, placing it in the suggestive-evidence tier for ACPA-positive RA specifically.

Jiang X et al. “An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis.” Rheumatology (oxford, England) (2016)

Allele C

OR 1.72

p 2.0e-6

N 4,336

Small GWAS

Swedish

▶

GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

▶

Research that mentions this SNP (2)

▶

Polymorphisms in the CTSH gene may influence the progression of diabetic retinopathy: a candidate-gene study in the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

AssociationN=130Steffen U. Thorsen et al.(2015)· Graefe's Archive for Clinical and Experimental Ophthalmology

This candidate gene study of 130 Danish children with type 1 diabetes examined associations between 20 diabetes-related SNPs and diabetic retinopathy progression over 16 years. The CTSH/rs3825932 variant was associated with reduced risk of progression to proliferative diabetic retinopathy (OR=0.20, p=2.4×10⁻³, p_adjust=0.048), while ERBB3/rs2292239 was associated with increased risk of two-step DR progression (OR=2.76, p=7.5×10⁻³, p_adjust=0.15). The CTSH association remained significant after multiple testing correction.

Traits studied:Diabetic retinopathyProliferative diabetic retinopathyType 1 diabetes mellitus

PubMed DOI Metascience Observatory

▶

Variability in Ethanol Biodisposition in Whites Is Modulated by Polymorphisms in the Adh1b and Adh1c Genes

ReviewCarmen Martínez et al.(2010)· Hepatology

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

Traits studied:Bone density/osteoporosisCaffeine sensitivityCardiovascular diseaseCeliac diseaseCerebrovascular diseaseCoronary heart diseaseDetoxification capacityEating behaviorGlucose homeostasisHistamine intoleranceInflammatory diseasesInsulin resistanceLactose intoleranceLeptin resistanceMetabolic syndromeNickel intoleranceObesityOsteoarthritisOverweightType 2 diabetes

rs7454108

Key Literature Trait Associations

Type 1 Diabetes

Pemphigus vulgaris

Celiac disease

ANCA-associated vasculitis

Rheumatoid arthritis

GWAS Catalog Trait Associations (2)

Research that mentions this SNP (2)

Community Wiki

Comments