A Functional Variant on 9p21.3 Related to Glioma Risk Affects Enhancer Activity and Modulates Expression of CDKN2B-AS1.
9p21.3
CDKN2B-AS1
GBM
GWAS
enhancer
functional variant
glioma
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
12
05
2021
received:
15
12
2020
accepted:
13
06
2021
pubmed:
22
6
2021
medline:
1
4
2022
entrez:
21
6
2021
Statut:
ppublish
Résumé
Genome-wide association studies have identified SNPs associated with glioma risk on 9p21.3, but biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 9p21.3 affects activity of an enhancer, causing altered expression of nearby genes. We considered all SNPs in linkage disequilibrium with the 9p21.3 sentinel SNP rs634537 that mapped to putative enhancers. An enhancer containing rs1537372 exhibited allele-specific effects on luciferase activity. Deletion of this enhancer in GBM cell lines correlated with decreased expression of CDKN2B-AS1. Expression quantitative trait loci analysis using non-diseased brain samples showed rs1537372 to be a consistently significant eQTL for CDKN2B-AS1. Additionally, our analysis of Hi-C data generated in neural progenitor cells showed that the bait region containing rs1537372 interacted with the CDKN2B-AS1 promoter. These data suggest rs1537372, a SNP at the 9p21.3 risk locus, is a functional variant that modulates expression of CDKN2B-AS1.
Identifiants
pubmed: 34153138
doi: 10.1002/humu.24244
pmc: PMC8519084
doi:
Substances chimiques
CDKN2B antisense RNA, human
0
RNA, Long Noncoding
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1208-1214Subventions
Organisme : NCI NIH HHS
ID : R01 CA207972
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA163177
Pays : United States
Informations de copyright
© 2021 The Authors. Human Mutation Published by Wiley Periodicals LLC.
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