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

被引：6
|
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
收藏
页码：1208 / 1214
页数：7
相关论文
共 34 条
  • [1] Association of a Chromosome Locus 9p21.3 CDKN2B-AS1 Variant rs4977574 with Hypertension: The TAMRISK Study
    Kunnas, Tarja
    Piesanen, Jaakko
    Nikkari, Seppo T.
    GENETIC TESTING AND MOLECULAR BIOMARKERS, 2018, 22 (05) : 327 - 330
  • [2] Effect of 9p21.3 (lncRNA and CDKN2A/2B) variant on lipid profile
    Wei, Baozhu
    Liu, Yang
    Li, Hang
    Peng, Yuanyuan
    Luo, Zhi
    FRONTIERS IN CARDIOVASCULAR MEDICINE, 2022, 9
  • [3] Identification and functional validation of an enhancer variant in the 9p21.3 locus associated with glaucoma risk and elevated expression of p16INK4a
    Zhu, Yizhou
    Tazearslan, Cagdas
    Rosenfeld, Michael G.
    Fiser, Andras
    Suh, Yousin
    AGING CELL, 2023, 22 (09)
  • [4] Chromosome 9p21.3 effect on CDKN2A/2B expression in human coronary atherosclerosis
    Notarangelo, F.
    Marziliano, N.
    Foco, L.
    Giacalone, R.
    Tardio, C.
    Coppini, L.
    Bontardelli, F.
    Berzuini, C.
    Merlini, P. A.
    Ardissino, D.
    EUROPEAN HEART JOURNAL, 2012, 33 : 873 - 873
  • [5] The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A
    Vijayakrishnan, Jayaram
    Henrion, Marc
    Moorman, Anthony V.
    Fiege, Bettina
    Kumar, Rajiv
    da Silva Filho, Miguel Inacio
    Holroyd, Amy
    Koehler, Rolf
    Thomsen, Hauke
    Irving, Julie A.
    Allan, James M.
    Lightfoot, Tracy
    Roman, Eve
    Kinsey, Sally E.
    Sheridan, Eamonn
    Thompson, Pamela D.
    Hoffmann, Per
    Noethen, Markus M.
    Muehleisen, Thomas W.
    Eisele, Lewin
    Bartram, Claus R.
    Schrappe, Martin
    Greaves, Mel
    Hemminki, Kari
    Harrison, Christine J.
    Stanulla, Martin
    Houlston, Richard S.
    SCIENTIFIC REPORTS, 2015, 5
  • [6] The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A
    Jayaram Vijayakrishnan
    Marc Henrion
    Anthony V. Moorman
    Bettina Fiege
    Rajiv Kumar
    Miguel Inacio da Silva Filho
    Amy Holroyd
    Rolf Koehler
    Hauke Thomsen
    Julie A. Irving
    James M. Allan
    Tracy Lightfoot
    Eve Roman
    Sally E. Kinsey
    Eamonn Sheridan
    Pamela D. Thompson
    Per Hoffmann
    Markus M. Nöthen
    Thomas W. Mühleisen
    Lewin Eisele
    Claus R. Bartram
    Martin Schrappe
    Mel Greaves
    Kari Hemminki
    Christine J. Harrison
    Martin Stanulla
    Richard S. Houlston
    Scientific Reports, 5
  • [7] Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk
    Sherborne, Amy L.
    Hosking, Fay J.
    Prasad, Rashmi B.
    Kumar, Rajiv
    Koehler, Rolf
    Vijayakrishnan, Jayaram
    Papaemmanuil, Elli
    Bartram, Claus R.
    Stanulla, Martin
    Schrappe, Martin
    Gast, Andreas
    Dobbins, Sara E.
    Ma, Yussanne
    Sheridan, Eamonn
    Taylor, Malcolm
    Kinsey, Sally E.
    Lightfoot, Tracey
    Roman, Eve
    Irving, Julie A. E.
    Allan, James M.
    Moorman, Anthony V.
    Harrison, Christine J.
    Tomlinson, Ian P.
    Richards, Sue
    Zimmermann, Martin
    Szalai, Csaba
    Semsei, Agnes F.
    Erdelyi, Daniel J.
    Krajinovic, Maja
    Sinnett, Daniel
    Healy, Jasmine
    Gonzalez Neira, Anna
    Kawamata, Norihiko
    Ogawa, Seishi
    Koeffler, H. Phillip
    Hemminki, Kari
    Greaves, Mel
    Houlston, Richard S.
    NATURE GENETICS, 2010, 42 (06) : 492 - 494
  • [8] Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk
    Amy L Sherborne
    Fay J Hosking
    Rashmi B Prasad
    Rajiv Kumar
    Rolf Koehler
    Jayaram Vijayakrishnan
    Elli Papaemmanuil
    Claus R Bartram
    Martin Stanulla
    Martin Schrappe
    Andreas Gast
    Sara E Dobbins
    Yussanne Ma
    Eamonn Sheridan
    Malcolm Taylor
    Sally E Kinsey
    Tracey Lightfoot
    Eve Roman
    Julie A E Irving
    James M Allan
    Anthony V Moorman
    Christine J Harrison
    Ian P Tomlinson
    Sue Richards
    Martin Zimmermann
    Csaba Szalai
    Ágnes F Semsei
    Daniel J Erdelyi
    Maja Krajinovic
    Daniel Sinnett
    Jasmine Healy
    Anna Gonzalez Neira
    Norihiko Kawamata
    Seishi Ogawa
    H Phillip Koeffler
    Kari Hemminki
    Mel Greaves
    Richard S Houlston
    Nature Genetics, 2010, 42 : 492 - 494
  • [9] A functional variant on 20q13.33 related to glioma risk alters enhancer activity and modulates expression of multiple genes
    Ali, Mourad Wagdy
    Patro, C. Pawan K.
    Zhu, Jacqueline Jufen
    Dampier, Christopher H.
    Plummer, Sarah J.
    Kuscu, Cem
    Adli, Mazhar
    Lau, Ching
    Lai, Rose K.
    Casey, Graham
    HUMAN MUTATION, 2021, 42 (01) : 77 - 88
  • [10] A functional variant rs1537373 in 9p21.3 region is associated with pancreatic cancer risk
    Zhu, Beibei
    Zhu, Ying
    Tian, Jianbo
    Shen, Na
    Li, Jiaoyuan
    Lou, Jiao
    Ke, Juntao
    Yang, Yang
    Gong, Yajie
    Gong, Jing
    Chang, Jiang
    Miao, Xiaoping
    Zhong, Rong
    MOLECULAR CARCINOGENESIS, 2019, 58 (05) : 760 - 766
1234