|(A;G)||1.2||1.2x higher risk for glioma development, 1.17x higher risk for atopic dermatitis in Han Chinese|
|(G;G)||1.4||1.4x higher risk for glioma development; but this is the common allele. 1.4x higher risk for atopic dermatitis in Han Chinese|
rs6010620’s association with AD was first identified in a genome-wide association study (GWAS) published in 2011, involving 491,905 autosomal SNPs in 1,012 cases and 1,362 controls from southern China followed by two replication studies — one with an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, the other had 1,806 cases and 3,256 controls from Germany [PMID 21666691]. rs6010620 showed evidence for AD association in both the combined Chinese population (minor/risk allele G; P = 3.00 × 10-8; OR = 1.17) and in the German cohort (minor allele A; risk allele G; P = 2.87 × 10-5; OR = 0.80).
The association was subsequently validated in a two-stage GWAS meta-analysis carried out later (P = 0.002; OR = 1.09; 95% CI 1.03–1.15) [PMID 22197932]. This GWAS involved 5,606 cases and 20,565 controls from 16 population-based cohorts of European descent in the discovery meta-analysis, and the ten most strongly associated new susceptibility loci were then examined in the replication meta-analysis encompassing an additional 5,419 affected individuals and 19,833 controls from 14 studies.
The group which published the first GWAS in 2011 recently validated the association as well with 4,538 cases and 13,412 controls from multiple cities in the central and northern parts of China (PGG = 1.83 × 10-7; OR = 1.40; 95% CI 1.23–1.58) [PMID 23838578]. rs6010620’s association with subphenotypes of AD was examined in this study, and the SNP showed significant protective effect for sporadic AD (Pgenotype = 0.01; PBonferroni = 0.006; OR = 0.60; 95% CI 0.43–0.83).
Tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) is an immune receptor that plays a regulatory role in suppressing cell death [PMID 14499341]. It has been shown that mRNA expression of serum TNFRSF6B in AD patients are higher than those in healthy individuals and control subjects with non-atopic inflammatory diseases [PMID 15282937]. ZGPAT, on the other hand, encodes the zinc finger CCCH-type with G patch domain-containing protein (ZIP) that transcriptionally represses several singling cascades including the epidermal growth factor receptor (EGFR) pathway [PMID 19644445]. EGFR is overexpressed in skin lesions of AD patients and inhibition of its signaling induces dysregulated chemokine profiles that augment skin inflammation [PMID 12819035]. Taken together, these results indicate that TNFRSF6B and ZGPAT are indeed plausible causal genes for AD, while further fine mapping and functional studies are still needed before an unequivocal conclusion can be made on the exact susceptibility genes at 20q13.33 [PMID 21666691].
23andMe blog rs6010620 G 1.28 Glioma
|Title||Genome-wide association study identifies five susceptibility loci for glioma|
|Odds Ratio||1.28 [1.21-1.35]|
|Title||Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility|
|Odds Ratio||1.52 [1.32-1.75]|
[PMID 20462933] Interaction between 5 genetic variants and allergy in glioma risk
[PMID 20847058] Genetic risk profiles identify different molecular etiologies for glioma
[PMID 20211558] Genetic advances in glioma: susceptibility genes and networks
[PMID 21350045] Association of sequence variants on chromosomes 20, 11, and 5 (20q13.33, 11q23.3, and 5p15.33) with glioma susceptibility in a Chinese population
|Title||Chromosome 7p11.2 (EGFR) variation influences glioma risk.|
|Odds Ratio||1.2400 [NR]|
[PMID 22448455] Genetic variant rs4982958 at 14q11.2 is associated with allergic rhinitis in a Chinese Han population running title: 14q11.2 is a susceptibility locus for allergic rhinitis
[PMID 22197932] Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis
[PMID 20212223] New insights into susceptibility to glioma.
[PMID 21666691] Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population.
[PMID 21825990] Genetic causes of glioma: new leads in the labyrinth.
[PMID 22387365] Fine mapping analysis of a region of 20q13.33 identified five independent susceptibility loci for glioma in a Chinese Han population.
|qualified_impact||Insufficiently evaluated pathogenic|
[PMID 23091480] Leveraging ethnic group incidence variation to investigate genetic susceptibility to glioma: a novel candidate SNP approach
|Title||Genome-wide association study of glioma and meta-analysis.|
|Odds Ratio||1.43 [1.28-1.59]|
[PMID 23115063] Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study
[PMID 23683922] RTEL1 tagging SNPs and haplotypes were associated with glioma development
[PMID 23161787] Association between glioma susceptibility loci and tumour pathology defines specific molecular etiologies
[PMID 23733245] Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis.
[PMID 23812731] RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.
[PMID 23838578] Genetic variants rs2393903 at 10q21.2 and rs6010620 at 20q13.33 are associated with clinical features of atopic dermatitis in the Chinese Han population
[PMID 25165198] Mutation-based molecular glioma classification: prevalence and association with germline risk snps
[PMID 25227808] Associations between the rs6010620 Polymorphism in RTEL1 and Risk of Glioma: a Meta-analysis of 20,711 Participants
|Title||Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk.|
|Odds Ratio||1.56 [1.42-1.72]|
[PMID 25556444] The RTEL1 rs6010620 Polymorphism and Glioma Risk: a Meta-analysis Based on 12 Case-control Studies
[PMID 25711310] Four genetic variants interact to confer susceptibility to atopic dermatitis in Chinese Han population
[PMID 25785045] Association between regulator of telomere elongation helicase 1 polymorphism and susceptibility to glioma
[PMID 26243184] An Updated and Comprehensive Meta-Analysis of Association Between Seven Hot Loci Polymorphisms from Eight GWAS and Glioma Risk
[PMID 26014354] CCDC26, CDKN2BAS, RTEL1 and TERT Polymorphisms in pediatric brain tumor susceptibility
[PMID 26839018] Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma.