ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS

被引：355

作者：

Pasmant, Eric ^{[1
,2
]}

Sabbagh, Audrey ^{[1
,2
]}

Vidaud, Michel ^{[1
,2
]}

Bieche, Ivan ^{[1
,2
]}

机构：

[1] Univ Paris 05, INSERM, UMR745, Fac Sci Pharmaceut & Biol, F-75006 Paris, France

[2] Hop Beaujon, Serv Biochim & Genet, Clichy, France

来源：

FASEB JOURNAL | 2011年 / 25卷 / 02期

关键词：

long ncRNA; susceptibility locus; p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; INTRACRANIAL ANEURYSM; SUSCEPTIBILITY LOCI; IDENTIFIES; RISK; MELANOMA; EXPRESSION; DELETION;

D O I：

10.1096/fj.10-172452

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A large noncoding RNA called ANRIL (for antisense noncoding RNA in the INK4 locus) has been identified within the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster. While the exact role of ANRIL awaited further elucidation, common disease genome-wide association studies (GWAS) have surprisingly identified the ANRIL gene as a genetic susceptibility locus shared associated by coronary disease, intracranial aneurysm and also type 2 diabetes. Expression studies have confirmed the coregulation of p15/CDKN2B, p16/CDKN2A, p14/ARF, and ANRIL. Among the cluster, ANRIL expression showed the strongest association with the multiple phenotypes linked to the 9p21.3 region. More recent GWAS also identified ANRIL as a risk locus for gliomas and basal cell carcinomas in accordance with the princeps observation. Moreover, a mouse model has confirmed the pivotal role of ANRIL in regulation of CDKN2A/B expression through a cis-acting mechanism and its implication in proliferation and senescence. The implication of ANRIL in cellular aging has provided an attractive unifying hypothesis to explain its association with various susceptibility risk factors. ANRIL identification emphasizes the underestimated role of long noncoding RNAs. Many GWAS have identified trait-associated SNPs that felt in noncoding genomic regions. It is conceivable to anticipate that long, noncoding RNAs will map to many of these "gene deserts."-Pasmant, E., Sabbagh, A., Vidaud, M., Bieche, I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 25, 444-448 (2011). www.fasebj.org

引用

页码：444 / 448

页数：5

共 30 条

[1] A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci [J].

Bei, Jin-Xin ;

Li, Yi ;

Jia, Wei-Hua ;

Feng, Bing-Jian ;

Zhou, Gangqiao ;

Chen, Li-Zhen ;

Feng, Qi-Sheng ;

Low, Hui-Qi ;

Zhang, Hongxing ;

He, Fuchu ;

Tai, E. Shyong ;

Kang, Tiebang ;

Liu, Edison T. ;

Liu, Jianjun ;

Zeng, Yi-Xin .

NATURE GENETICS, 2010, 42 (07) :599-U173

[2] Approaches to microRNA discovery [J].

Berezikov, Eugene ;

Cuppen, Edwin ;

Plasterk, Ronald H. A. .

NATURE GENETICS, 2006, 38 (Suppl 6) :S2-S7

[3] Susceptibility loci for intracranial aneurysm in European and Japanese populations [J].

Bilguvar, Kaya ;

Yasuno, Katsuhito ;

Niemela, Mika ;

Ruigrok, Ynte M. ;

Fraunberg, Mikael von und zu ;

van Duijn, Cornelia M. ;

van den Berg, Leonard H. ;

Mane, Shrikant ;

Mason, Christopher E. ;

Choi, Murim ;

Gaal, Emilia ;

Bayri, Yasar ;

Kolb, Luis ;

Arlier, Zulfikar ;

Ravuri, Sudhakar ;

Ronkainen, Antti ;

Tajima, Atsushi ;

Laakso, Aki ;

Hata, Akira ;

Kasuya, Hidetoshi ;

Koivisto, Timo ;

Rinne, Jaakko ;

Ohman, Juha ;

Breteler, Monique M. B. ;

Wijmenga, Cisca ;

State, Matthew W. ;

Rinkel, Gabriel J. E. ;

Hernesniemi, Juha ;

Jaaskelainen, Juha E. ;

Palotie, Aarno ;

Inoue, Ituro ;

Lifton, Richard P. ;

Guenel, Murat .

NATURE GENETICS, 2008, 40 (12) :1472-1477

[4] Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p [J].

Broadbent, Helen M. ;

Peden, John F. ;

Lorkowski, Stefan ;

Goel, Anuj ;

Ongen, Halit ;

Green, Fiona ;

Clarke, Robert ;

Collins, Rory ;

Franzosi, Maria Grazia ;

Tognoni, Gianni ;

Seedorf, Udo ;

Rust, Stephan ;

Eriksson, Per ;

Hamsten, Anders ;

Farrall, Martin ;

Watkins, Hugh .

HUMAN MOLECULAR GENETICS, 2008, 17 (06) :806-814

[5] Chromosome 9p21 SNPs Associated with Multiple Disease Phenotypes Correlate with ANRIL Expression [J].

Cunnington, Michael S. ;

Koref, Mauro Santibanez ;

Mayosi, Bongani M. ;

Burn, John ;

Keavney, Bernard .

PLOS GENETICS, 2010, 6 (04)

[6] Relationship between CAD Risk Genotype in the Chromosome 9p21 Locus and Gene Expression. Identification of Eight New ANRIL Splice Variants [J].

Folkersen, Lasse ;

Kyriakou, Theodosios ;

Goel, Anuj ;

Peden, John ;

Malarstig, Anders ;

Paulsson-Berne, Gabrielle ;

Hamsten, Anders ;

Franco-Cereceda, Anders ;

Gabrielsen, Anders ;

Eriksson, Per ;

Watkins, Hugh .

PLOS ONE, 2009, 4 (11)

[7] Genetics of melanoma predisposition [J].

Hayward, NK .

ONCOGENE, 2003, 22 (20) :3053-3062

[8] The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm [J].

Helgadottir, Anna ;

Thorleifsson, Gudmar ;

Magnusson, Kristinn P. ;

Gretarsdottir, Solveig ;

Steinthorsdottir, Valgerdur ;

Manolescu, Andrei ;

Jones, Gregory T. ;

Rinkel, Gabriel J. E. ;

Blankensteijn, Jan D. ;

Ronkainen, Antti ;

Jaaskelainen, Juha E. ;

Kyo, Yoshiki ;

Lenk, Guy M. ;

Sakalihasan, Natzi ;

Kostulas, Konstantinos ;

Gottsater, Anders ;

Flex, Andrea ;

Stefansson, Hreinn ;

Hansen, Torben ;

Andersen, Gitte ;

Weinsheimer, Shantel ;

Borch-Johnsen, Knut ;

Jorgensen, Torben ;

Shah, Svati H. ;

Quyyumi, Arshed A. ;

Granger, Christopher B. ;

Reilly, Muredach P. ;

Austin, Harland ;

Levey, Allan I. ;

Vaccarino, Viola ;

Palsdottir, Ebba ;

Walters, G. Bragi ;

Jonsdottir, Thorbjorg ;

Snorradottir, Steinunn ;

Magnusdottir, Dana ;

Gudmundsson, Gudmundur ;

Ferrell, Robert E. ;

Sveinbjornsdottir, Sigurlaug ;

Hernesniemi, Juha ;

Niemela, Mika ;

Limet, Raymond ;

Andersen, Karl ;

Sigurdsson, Gunnar ;

Benediktsson, Rafn ;

Verhoeven, Eric L. G. ;

Teijink, Joep A. W. ;

Grobbee, Diederick E. ;

Rader, Daniel J. ;

Collier, David A. ;

Pedersen, Oluf .

NATURE GENETICS, 2008, 40 (02) :217-224

[9] ANRIL Expression Is Associated With Atherosclerosis Risk at Chromosome 9p21 [J].

Holdt, Lesca M. ;

Beutner, Frank ;

Scholz, Markus ;

Gielen, Stephan ;

Gaebel, Gabor ;

Bergert, Hendrik ;

Schuler, Gerhard ;

Thiery, Joachim ;

Teupser, Daniel .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2010, 30 (03) :620-U518

[10] Functional Analysis of the Chromosome 9p21.3 Coronary Artery Disease Risk Locus [J].

Jarinova, Olga ;

Stewart, Alexandre F. R. ;

Roberts, Robert ;

Wells, George ;

Lau, Paulina ;

Naing, Thet ;

Buerki, Christine ;

McLean, Bradley W. ;

Cook, Richard C. ;

Parker, Joel S. ;

McPherson, Ruth .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2009, 29 (10) :1671-U670

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