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Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma
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2019 (Engelska)Ingår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 79, nr 8, s. 2065-2071Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 x 10(-6), candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 x 10(-6)). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.

Significance: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.

Ort, förlag, år, upplaga, sidor
American Association for Cancer Research , 2019. Vol. 79, nr 8, s. 2065-2071
Nationell ämneskategori
Medicinsk genetik Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:umu:diva-158571DOI: 10.1158/0008-5472.CAN-18-2888ISI: 000464651500032PubMedID: 30709929OAI: oai:DiVA.org:umu-158571DiVA, id: diva2:1318406
Tillgänglig från: 2019-05-27 Skapad: 2019-05-27 Senast uppdaterad: 2019-05-27Bibliografiskt granskad

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Melin, Beatrice S.

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Il'yasova, DoraBarnholtz-Sloan, Jill S.Melin, Beatrice S.
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Institutionen för strålningsvetenskaper
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Cancer Research
Medicinsk genetikCancer och onkologi

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