A Functional Variant on 9p21.3 Related to Glioma Risk Affects Enhancer Activity and Modulates Expression of CDKN2B-AS1

被引：7

作者：

Ali, Mourad Wagdy ^{[1
]}

Patro, C. Pawan K. ^{[2
]}

Devall, Matthew ^{[1
]}

Dampier, Christopher H. ^{[1
]}

Plummer, Sarah J. ^{[1
]}

Kuscu, Cem ^{[3
]}

Adli, Mazhar ^{[4
]}

Lai, Rose K. ^{[5
,6
]}

Casey, Graham ^{[1
]}

机构：

[1] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA

[2] Univ Southern Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA

[3] Univ Tennessee, James D Eason Transplant Res Inst, Dept Surg, Memphis, TN 38163 USA

[4] Northwestern Univ, Feinberg Sch Med, Robert Lurie Comprehens Canc Ctr, Dept Obstet & Gynecol, Chicago, IL 60611 USA

[5] Univ Southern Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA

[6] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA

来源：

HUMAN MUTATION | 2021年 / 42卷 / 10期

关键词：

9p21; 3; CDKN2B-AS1; enhancer; functional variant; GBM; glioma; GWAS; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; LONG NONCODING RNA; SUSCEPTIBILITY LOCI; BRAIN;

D O I：

10.1002/humu.24244

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1208 / 1214

页数：7

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