Genome-wide association analysis identifies a meningioma risk locus at 11p15.5

被引：20

作者：

Claus, Elizabeth B. ^{[1
,2
]}

Cornish, Alex J. ^{[3
]}

Broderick, Peter ^{[3
]}

Schildkraut, Joellen M. ^{[4
]}

Dobbins, Sara E. ^{[3
]}

Holroyd, Amy ^{[3
]}

Calvocoressi, Lisa ^{[1
]}

Lu, Lingeng ^{[1
]}

Hansen, Helen M. ^{[5
]}

Smirnov, Ivan ^{[5
]}

Walsh, Kyle M. ^{[5
]}

Schramm, Johannes ^{[6
]}

Hoffmann, Per ^{[7
,8
]}

Nothen, Markus M. ^{[8
,9
,10
]}

Jockel, Karl-Heinz ^{[11
]}

Swerdlow, Anthony ^{[3
,12
]}

Larsen, Signe Benzon ^{[13
]}

Johansen, Christoffer ^{[13
]}

Simon, Matthias ^{[6
,14
]}

Bondy, Melissa ^{[15
,16
]}

Wrensch, Margaret ^{[5
,17
]}

Houlston, Richard S. ^{[3
]}

Wiemels, Joseph L. ^{[5
,17
,18
]}

机构：

[1] Yale Univ, Sch Publ Hlth, New Haven, CT USA

[2] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA

[3] Inst Canc Res, Div Genet & Epidemiol, 15 Cotswold Rd, London SM2 5NG, England

[4] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA

[5] Univ Calif San Francisco, Dept Neurol Surg, Div Neuroepidemiol, San Francisco, CA 94143 USA

[6] Univ Bonn, Med Sch, Bonn, Germany

[7] Univ Basel, Dept Biomed, Human Genom Res Grp, Basel, Switzerland

[8] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany

[9] Univ Bonn, Sch Med, Inst Human Genet, Bonn, Germany

[10] Univ Hosp Bonn, Bonn, Germany

[11] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany

[12] Inst Canc Res, Div Breast Canc Res, London, England

[13] Danish Canc Soc Res Ctr, Unit Survivorship, Copenhagen, Denmark

[14] Bethel Clin, Dept Neurosurg, Bielefeld, Germany

[15] Baylor Coll Med, Dept Med, Sect Epidemiol & Populat Sci, Houston, TX 77030 USA

[16] Baylor Coll Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA

[17] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[18] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

来源：

NEURO-ONCOLOGY | 2018年 / 20卷 / 11期

关键词：

genome-wide association study; meningioma; polygenic; risk; single-nucleotide polymorphism; GENETIC EPIDEMIOLOGY RESEARCH; NERVOUS-SYSTEM TUMORS; END RESULTS PROGRAM; QUALITY-CONTROL; ADULT HEALTH; COMMON SNPS; CANCER; BRAIN; HERITABILITY; SURVEILLANCE;

D O I：

10.1093/neuonc/noy077

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background. Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. Methods. To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12 081 controls. Results. We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 x 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges. Conclusions. This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.

引用

页码：1485 / 1493

页数：9

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