Functional analysis of low-grade glioma genetic variants predicts key target genes and transcription factors
Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals' risk to various diseases, including cancer. At least 25 risk loci have been identified for low-grade gliomas (LGGs), but their molecular functions remain largely...
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Published in | Neuro-oncology (Charlottesville, Va.) Vol. 23; no. 4; pp. 638 - 649 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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England
Oxford University Press
12.04.2021
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Abstract | Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals' risk to various diseases, including cancer. At least 25 risk loci have been identified for low-grade gliomas (LGGs), but their molecular functions remain largely unknown.
We hypothesized that GWAS loci contain causal single nucleotide polymorphisms (SNPs) that reside in accessible open chromatin regions and modulate the expression of target genes by perturbing the binding affinity of transcription factors (TFs). We performed an integrative analysis of genomic and epigenomic data from The Cancer Genome Atlas and other public repositories to identify candidate causal SNPs within linkage disequilibrium blocks of LGG GWAS loci. We assessed their potential regulatory role via in silico TF binding sequence perturbations, convolutional neural network trained on TF binding data, and simulated annealing-based interpretation methods.
We built an interactive website (http://education.knoweng.org/alg3/) summarizing the functional footprinting of 280 variants in 25 LGG GWAS regions, providing rich information for further computational and experimental scrutiny. We identified as case studies PHLDB1 and SLC25A26 as candidate target genes of rs12803321 and rs11706832, respectively, and predicted the GWAS variant rs648044 to be the causal SNP modulating ZBTB16, a known tumor suppressor in multiple cancers. We showed that rs648044 likely perturbed the binding affinity of the TF MAFF, as supported by RNA interference and in vitro MAFF binding experiments.
The identified candidate (causal SNP, target gene, TF) triplets and the accompanying resource will help accelerate our understanding of the molecular mechanisms underlying genetic risk factors for gliomas. |
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AbstractList | Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals' risk to various diseases, including cancer. At least 25 risk loci have been identified for low-grade gliomas (LGGs), but their molecular functions remain largely unknown.
We hypothesized that GWAS loci contain causal single nucleotide polymorphisms (SNPs) that reside in accessible open chromatin regions and modulate the expression of target genes by perturbing the binding affinity of transcription factors (TFs). We performed an integrative analysis of genomic and epigenomic data from The Cancer Genome Atlas and other public repositories to identify candidate causal SNPs within linkage disequilibrium blocks of LGG GWAS loci. We assessed their potential regulatory role via in silico TF binding sequence perturbations, convolutional neural network trained on TF binding data, and simulated annealing-based interpretation methods.
We built an interactive website (http://education.knoweng.org/alg3/) summarizing the functional footprinting of 280 variants in 25 LGG GWAS regions, providing rich information for further computational and experimental scrutiny. We identified as case studies PHLDB1 and SLC25A26 as candidate target genes of rs12803321 and rs11706832, respectively, and predicted the GWAS variant rs648044 to be the causal SNP modulating ZBTB16, a known tumor suppressor in multiple cancers. We showed that rs648044 likely perturbed the binding affinity of the TF MAFF, as supported by RNA interference and in vitro MAFF binding experiments.
The identified candidate (causal SNP, target gene, TF) triplets and the accompanying resource will help accelerate our understanding of the molecular mechanisms underlying genetic risk factors for gliomas. Abstract Background Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals’ risk to various diseases, including cancer. At least 25 risk loci have been identified for low-grade gliomas (LGGs), but their molecular functions remain largely unknown. Methods We hypothesized that GWAS loci contain causal single nucleotide polymorphisms (SNPs) that reside in accessible open chromatin regions and modulate the expression of target genes by perturbing the binding affinity of transcription factors (TFs). We performed an integrative analysis of genomic and epigenomic data from The Cancer Genome Atlas and other public repositories to identify candidate causal SNPs within linkage disequilibrium blocks of LGG GWAS loci. We assessed their potential regulatory role via in silico TF binding sequence perturbations, convolutional neural network trained on TF binding data, and simulated annealing–based interpretation methods. Results We built an interactive website (http://education.knoweng.org/alg3/) summarizing the functional footprinting of 280 variants in 25 LGG GWAS regions, providing rich information for further computational and experimental scrutiny. We identified as case studies PHLDB1 and SLC25A26 as candidate target genes of rs12803321 and rs11706832, respectively, and predicted the GWAS variant rs648044 to be the causal SNP modulating ZBTB16, a known tumor suppressor in multiple cancers. We showed that rs648044 likely perturbed the binding affinity of the TF MAFF, as supported by RNA interference and in vitro MAFF binding experiments. Conclusions The identified candidate (causal SNP, target gene, TF) triplets and the accompanying resource will help accelerate our understanding of the molecular mechanisms underlying genetic risk factors for gliomas. |
Author | McKinney, Andrew M Costello, Joseph F Selvin, Paul R Youn, Yeoan Zazubovich, Valter Zhang, Yi Manjunath, Mohith Eckel-Passow, Jeanette Kollmeyer, Thomas M Song, Jun S Yan, Jialu Drucker, Kristen L Jenkins, Robert B |
AuthorAffiliation | 4 Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, Minnesota, USA 8 Department of Health Sciences Research, Mayo Clinic , Rochester, Minnesota, USA 3 Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA 5 Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA 6 Department of Physics, Concordia University , Montreal, Québec, Canada 2 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA 1002 Department of Data Sciences, Dana-Farber Cancer Institute , Boston, Massachusetts, USA 1 Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA 7 Department of Bioengineering, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA |
AuthorAffiliation_xml | – name: 1 Department of Physics, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA – name: 6 Department of Physics, Concordia University , Montreal, Québec, Canada – name: 7 Department of Bioengineering, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA – name: 5 Department of Neurological Surgery, University of California San Francisco , San Francisco, California, USA – name: 2 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA – name: 4 Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, Minnesota, USA – name: 3 Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA – name: 8 Department of Health Sciences Research, Mayo Clinic , Rochester, Minnesota, USA – name: 1002 Department of Data Sciences, Dana-Farber Cancer Institute , Boston, Massachusetts, USA |
Author_xml | – sequence: 1 givenname: Mohith surname: Manjunath fullname: Manjunath, Mohith organization: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA – sequence: 2 givenname: Jialu surname: Yan fullname: Yan, Jialu organization: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA – sequence: 3 givenname: Yeoan surname: Youn fullname: Youn, Yeoan organization: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA – sequence: 4 givenname: Kristen L surname: Drucker fullname: Drucker, Kristen L organization: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA – sequence: 5 givenname: Thomas M surname: Kollmeyer fullname: Kollmeyer, Thomas M organization: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA – sequence: 6 givenname: Andrew M surname: McKinney fullname: McKinney, Andrew M organization: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA – sequence: 7 givenname: Valter surname: Zazubovich fullname: Zazubovich, Valter organization: Department of Physics, Concordia University, Montreal, Québec, Canada – sequence: 8 givenname: Yi surname: Zhang fullname: Zhang, Yi organization: Department of Data Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA – sequence: 9 givenname: Joseph F surname: Costello fullname: Costello, Joseph F organization: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA – sequence: 10 givenname: Jeanette surname: Eckel-Passow fullname: Eckel-Passow, Jeanette organization: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA – sequence: 11 givenname: Paul R surname: Selvin fullname: Selvin, Paul R organization: Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA – sequence: 12 givenname: Robert B surname: Jenkins fullname: Jenkins, Robert B organization: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA – sequence: 13 givenname: Jun S surname: Song fullname: Song, Jun S organization: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA |
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CitedBy_id | crossref_primary_10_1007_s10067_022_06103_4 crossref_primary_10_18632_oncotarget_28451 crossref_primary_10_1016_j_jgg_2023_01_008 crossref_primary_10_3389_or_2024_1379323 crossref_primary_10_3390_cancers13174299 crossref_primary_10_1155_2023_3678327 crossref_primary_10_1038_s41598_023_33923_4 crossref_primary_10_3390_biomedicines12010008 crossref_primary_10_3389_fonc_2021_698993 crossref_primary_10_1136_jmg_2022_108763 |
Cites_doi | 10.7554/eLife.40364 10.1038/srep17367 10.1007/s00401-018-1825-z 10.1038/ng.3721 10.18632/oncotarget.102 10.1126/science.aay0793 10.1042/bj20031664 10.1371/journal.pgen.1005937 10.1242/jcs.003129 10.1007/s00401-016-1545-1 10.1093/bioinformatics/btr064 10.1093/nar/gkaa161 10.1038/ng.407 10.1158/0008-5472.CAN-14-3602 10.1093/bioinformatics/btv402 10.1111/j.2517-6161.1995.tb02031.x 10.1371/journal.pcbi.1005836 10.1056/NEJMp1607591 10.1056/NEJMoa1407279 10.3727/096504018X15231148037228 10.1093/hmg/ddr192 10.1016/j.cell.2015.12.028 10.1038/ng.3823 10.1186/1423-0127-20-98 10.18632/oncotarget.19813 10.1158/0008-5472.CAN-17-3486 10.1126/science.aav1898 10.1111/febs.14028 10.1038/nature14248 10.1093/neuonc/noz009 10.1038/nature11247 10.1056/NEJMoa1402121 10.1038/s41419-017-0107-3 10.1093/nar/gkw1133 10.1093/nar/gkw1061 10.1186/s13148-018-0590-0 10.1158/0008-5472.CAN-18-2888 10.1038/sj.onc.1207597 10.1038/nbt.3300 10.1093/nar/gky080 10.1038/ncomms9559 |
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Copyright | The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2020 |
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Keywords | genetic variants functional genomics GWAS low-grade glioma |
Language | English |
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Notes | Mohith Manjunath and Jialu Yan contributed equally to this work. |
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References | Kundaje (2021041218434566200_CIT0010) 2015; 518 ENCODE Project Consortium (2021041218434566200_CIT0009) 2012; 489 Machiela (2021041218434566200_CIT0011) 2015; 31 Shete (2021041218434566200_CIT0003) 2009; 41 Bonder (2021041218434566200_CIT0043) 2017; 49 Finnegan (2021041218434566200_CIT0019) 2017; 13 Felicetti (2021041218434566200_CIT0033) 2004; 23 Sun (2021041218434566200_CIT0041) 2018; 10 Shen (2021041218434566200_CIT0025) 2018; 9 Labreche (2021041218434566200_CIT0028) 2018; 135 Brat (2021041218434566200_CIT0014) 2015; 372 Fornes (2021041218434566200_CIT0027) 2020; 48 Grant (2021041218434566200_CIT0029) 2011; 27 Koubi (2021041218434566200_CIT0032) 2018; 46 Agrimi (2021041218434566200_CIT0039) 2004; 379 Ceccarelli (2021041218434566200_CIT0015) 2016; 164 Melin (2021041218434566200_CIT0006) 2017; 49 Alipanahi (2021041218434566200_CIT0037) 2015; 33 Hsieh (2021041218434566200_CIT0023) 2015; 75 Baskin (2021041218434566200_CIT0008) 2015; 5 Kommagani (2021041218434566200_CIT0036) 2016; 12 Agrawal Singh (2021041218434566200_CIT0035) 2019; 8 Eckel-Passow (2021041218434566200_CIT0002) 2015; 372 Corces (2021041218434566200_CIT0020) 2018; 362 Atkins (2021041218434566200_CIT0007) 2019; 79 Benjamini (2021041218434566200_CIT0016) 1995; 57 Grossman (2021041218434566200_CIT0013) 2016; 375 Zhang (2021041218434566200_CIT0017) 2018; 78 Nott (2021041218434566200_CIT0021) 2019; 366 Jin (2021041218434566200_CIT0026) 2017; 8 Finnegan (2021041218434566200_CIT0018) 2020; 48 Wang (2021041218434566200_CIT0024) 2019; 41 Louis (2021041218434566200_CIT0001) 2016; 131 Kinnersley (2021041218434566200_CIT0005) 2015; 6 Sanson (2021041218434566200_CIT0004) 2011; 20 Eckel-Passow (2021041218434566200_CIT0012) 2019; 21 Nawshad (2021041218434566200_CIT0030) 2007; 120 WashU (2021041218434566200_CIT0031) 2019 Menga (2021041218434566200_CIT0040) 2017; 284 Hobbs (2021041218434566200_CIT0034) 2010; 1 MacArthur (2021041218434566200_CIT0042) 2017; 45 Lin (2021041218434566200_CIT0022) 2013; 20 Schmidt (2021041218434566200_CIT0038) 2017; 45 |
References_xml | – volume: 8 start-page: e40364 year: 2019 ident: 2021041218434566200_CIT0035 article-title: PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells publication-title: Elife. doi: 10.7554/eLife.40364 contributor: fullname: Agrawal Singh – volume: 5 start-page: 17367 year: 2015 ident: 2021041218434566200_CIT0008 article-title: Functional analysis of the 11q23.3 glioma susceptibility locus implicates PHLDB1 and DDX6 in glioma susceptibility publication-title: Sci Rep. doi: 10.1038/srep17367 contributor: fullname: Baskin – volume: 135 start-page: 743 issue: 5 year: 2018 ident: 2021041218434566200_CIT0028 article-title: Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci publication-title: Acta Neuropathol. doi: 10.1007/s00401-018-1825-z contributor: fullname: Labreche – volume: 49 start-page: 131 issue: 1 year: 2017 ident: 2021041218434566200_CIT0043 article-title: Disease variants alter transcription factor levels and methylation of their binding sites publication-title: Nat Genet. doi: 10.1038/ng.3721 contributor: fullname: Bonder – volume: 1 start-page: 3 issue: 1 year: 2010 ident: 2021041218434566200_CIT0034 article-title: Shape-shifting and tumor suppression by PLZF publication-title: Oncotarget. doi: 10.18632/oncotarget.102 contributor: fullname: Hobbs – volume: 366 start-page: 1134 issue: 6469 year: 2019 ident: 2021041218434566200_CIT0021 article-title: Brain cell type-specific enhancer-promoter interactome maps and disease-risk association publication-title: Science. doi: 10.1126/science.aay0793 contributor: fullname: Nott – volume: 379 start-page: 183 issue: Pt 1 year: 2004 ident: 2021041218434566200_CIT0039 article-title: Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution publication-title: Biochem J. doi: 10.1042/bj20031664 contributor: fullname: Agrimi – volume: 12 start-page: e1005937 issue: 4 year: 2016 ident: 2021041218434566200_CIT0036 article-title: The promyelocytic leukemia zinc finger transcription factor is critical for human endometrial stromal cell decidualization publication-title: PLoS Genet. doi: 10.1371/journal.pgen.1005937 contributor: fullname: Kommagani – volume: 120 start-page: 1646 issue: Pt 9 year: 2007 ident: 2021041218434566200_CIT0030 article-title: TGFbeta3 inhibits E-cadherin gene expression in palate medial-edge epithelial cells through a Smad2-Smad4-LEF1 transcription complex publication-title: J Cell Sci. doi: 10.1242/jcs.003129 contributor: fullname: Nawshad – volume: 131 start-page: 803 issue: 6 year: 2016 ident: 2021041218434566200_CIT0001 article-title: The 2016 World Health Organization classification of tumors of the central nervous system: a summary publication-title: Acta Neuropathol. doi: 10.1007/s00401-016-1545-1 contributor: fullname: Louis – volume: 27 start-page: 1017 issue: 7 year: 2011 ident: 2021041218434566200_CIT0029 article-title: FIMO: scanning for occurrences of a given motif publication-title: Bioinformatics. doi: 10.1093/bioinformatics/btr064 contributor: fullname: Grant – volume: 48 start-page: 4081 issue: 8 year: 2020 ident: 2021041218434566200_CIT0018 article-title: Epigenetic engineering of yeast reveals dynamic molecular adaptation to methylation stress and genetic modulators of specific DNMT3 family members publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkaa161 contributor: fullname: Finnegan – volume: 41 start-page: 899 issue: 8 year: 2009 ident: 2021041218434566200_CIT0003 article-title: Genome-wide association study identifies five susceptibility loci for glioma publication-title: Nat Genet. doi: 10.1038/ng.407 contributor: fullname: Shete – volume: 75 start-page: 1944 issue: 10 year: 2015 ident: 2021041218434566200_CIT0023 article-title: PLZF, a tumor suppressor genetically lost in metastatic castration-resistant prostate cancer, is a mediator of resistance to androgen deprivation therapy publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-14-3602 contributor: fullname: Hsieh – volume: 31 start-page: 3555 issue: 21 year: 2015 ident: 2021041218434566200_CIT0011 article-title: LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants publication-title: Bioinformatics. doi: 10.1093/bioinformatics/btv402 contributor: fullname: Machiela – volume: 57 start-page: 289 issue: 1 year: 1995 ident: 2021041218434566200_CIT0016 article-title: Controlling the false discovery rate: a practical and powerful approach to multiple testing publication-title: J R Stat Soc Ser B. doi: 10.1111/j.2517-6161.1995.tb02031.x contributor: fullname: Benjamini – volume: 13 start-page: e1005836 issue: 10 year: 2017 ident: 2021041218434566200_CIT0019 article-title: Maximum entropy methods for extracting the learned features of deep neural networks publication-title: PLoS Comput Biol. doi: 10.1371/journal.pcbi.1005836 contributor: fullname: Finnegan – volume: 48 start-page: D87 issue: D1 year: 2020 ident: 2021041218434566200_CIT0027 article-title: JASPAR 2020: update of the open-access database of transcription factor binding profiles publication-title: Nucleic Acids Res. contributor: fullname: Fornes – volume: 375 start-page: 1109 issue: 12 year: 2016 ident: 2021041218434566200_CIT0013 article-title: Toward a shared vision for cancer genomic data publication-title: N Engl J Med. doi: 10.1056/NEJMp1607591 contributor: fullname: Grossman – volume: 372 start-page: 2499 issue: 26 year: 2015 ident: 2021041218434566200_CIT0002 article-title: Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors publication-title: N Engl J Med. doi: 10.1056/NEJMoa1407279 contributor: fullname: Eckel-Passow – volume: 41 start-page: 1007 issue: 2 year: 2019 ident: 2021041218434566200_CIT0024 article-title: Tumor suppressor PLZF regulated by lncRNA ANRIL suppresses proliferation and epithelial mesenchymal transformation of gastric cancer cells publication-title: Oncol Rep. doi: 10.3727/096504018X15231148037228 contributor: fullname: Wang – volume: 20 start-page: 2897 issue: 14 year: 2011 ident: 2021041218434566200_CIT0004 article-title: Chromosome 7p11.2 (EGFR) variation influences glioma risk publication-title: Hum Mol Genet. doi: 10.1093/hmg/ddr192 contributor: fullname: Sanson – volume: 164 start-page: 550 issue: 3 year: 2016 ident: 2021041218434566200_CIT0015 article-title: Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma publication-title: Cell. doi: 10.1016/j.cell.2015.12.028 contributor: fullname: Ceccarelli – volume: 49 start-page: 789 issue: 5 year: 2017 ident: 2021041218434566200_CIT0006 article-title: Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors publication-title: Nat Genet. doi: 10.1038/ng.3823 contributor: fullname: Melin – volume: 20 start-page: 98 year: 2013 ident: 2021041218434566200_CIT0022 article-title: Analysis of the interaction between zinc finger protein 179 (Znf179) and promyelocytic leukemia zinc finger (Plzf) publication-title: J Biomed Sci. doi: 10.1186/1423-0127-20-98 contributor: fullname: Lin – volume: 8 start-page: 71317 issue: 41 year: 2017 ident: 2021041218434566200_CIT0026 article-title: Role of PLZF as a tumor suppressor in prostate cancer publication-title: Oncotarget. doi: 10.18632/oncotarget.19813 contributor: fullname: Jin – volume: 78 start-page: 1579 issue: 7 year: 2018 ident: 2021041218434566200_CIT0017 article-title: Integrative genomic analysis predicts causative cis-regulatory mechanisms of the breast cancer-associated genetic variant rs4415084 publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-17-3486 contributor: fullname: Zhang – volume: 362 start-page: eaav1898 issue: 6413 year: 2018 ident: 2021041218434566200_CIT0020 article-title: The chromatin accessibility landscape of primary human cancers publication-title: Science. doi: 10.1126/science.aav1898 contributor: fullname: Corces – volume: 284 start-page: 967 issue: 6 year: 2017 ident: 2021041218434566200_CIT0040 article-title: SLC25A26 overexpression impairs cell function via mtDNA hypermethylation and rewiring of methyl metabolism publication-title: FEBS J. doi: 10.1111/febs.14028 contributor: fullname: Menga – volume: 518 start-page: 317 issue: 7539 year: 2015 ident: 2021041218434566200_CIT0010 article-title: Integrative analysis of 111 reference human epigenomes publication-title: Nature. doi: 10.1038/nature14248 contributor: fullname: Kundaje – volume: 21 start-page: 451 issue: 4 year: 2019 ident: 2021041218434566200_CIT0012 article-title: Using germline variants to estimate glioma and subtype risks publication-title: Neuro Oncol. doi: 10.1093/neuonc/noz009 contributor: fullname: Eckel-Passow – volume: 489 start-page: 57 issue: 7414 year: 2012 ident: 2021041218434566200_CIT0009 article-title: An integrated encyclopedia of DNA elements in the human genome publication-title: Nature. doi: 10.1038/nature11247 contributor: fullname: ENCODE Project Consortium – volume: 372 start-page: 2481 issue: 26 year: 2015 ident: 2021041218434566200_CIT0014 article-title: Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas publication-title: N Engl J Med. doi: 10.1056/NEJMoa1402121 contributor: fullname: Brat – volume: 9 start-page: 71 issue: 2 year: 2018 ident: 2021041218434566200_CIT0025 article-title: PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2 publication-title: Cell Death Dis. doi: 10.1038/s41419-017-0107-3 contributor: fullname: Shen – volume: 45 start-page: D896 issue: D1 year: 2017 ident: 2021041218434566200_CIT0042 article-title: The new NHGRI-EBI catalog of published genome-wide association studies (GWAS Catalog) publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkw1133 contributor: fullname: MacArthur – volume: 45 start-page: 54 issue: 1 year: 2017 ident: 2021041218434566200_CIT0038 article-title: Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkw1061 contributor: fullname: Schmidt – volume: 10 start-page: 157 issue: 1 year: 2018 ident: 2021041218434566200_CIT0041 article-title: The degree of mitochondrial DNA methylation in tumor models of glioblastoma and osteosarcoma publication-title: Clin Epigenetics. doi: 10.1186/s13148-018-0590-0 contributor: fullname: Sun – volume: 79 start-page: 2065 issue: 8 year: 2019 ident: 2021041218434566200_CIT0007 article-title: Transcriptome-wide association study identifies new candidate susceptibility genes for glioma publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-18-2888 contributor: fullname: Atkins – volume: 23 start-page: 4567 issue: 26 year: 2004 ident: 2021041218434566200_CIT0033 article-title: Role of PLZF in melanoma progression publication-title: Oncogene. doi: 10.1038/sj.onc.1207597 contributor: fullname: Felicetti – volume: 33 start-page: 831 issue: 8 year: 2015 ident: 2021041218434566200_CIT0037 article-title: Predicting the sequence specificities of DNA- and RNA-binding proteins by deep learning publication-title: Nat Biotechnol. doi: 10.1038/nbt.3300 contributor: fullname: Alipanahi – volume: 46 start-page: 3339 issue: 7 year: 2018 ident: 2021041218434566200_CIT0032 article-title: Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity publication-title: Nucleic Acids Res. doi: 10.1093/nar/gky080 contributor: fullname: Koubi – year: 2019 ident: 2021041218434566200_CIT0031 contributor: fullname: WashU – volume: 6 start-page: 8559 year: 2015 ident: 2021041218434566200_CIT0005 article-title: Genome-wide association study identifies multiple susceptibility loci for glioma publication-title: Nat Commun. doi: 10.1038/ncomms9559 contributor: fullname: Kinnersley |
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Snippet | Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals' risk to various diseases,... Abstract Background Large-scale genome-wide association studies (GWAS) have implicated thousands of germline genetic variants in modulating individuals’ risk... |
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SubjectTerms | Amino Acid Transport Systems Basic and Translational Investigations Calcium-Binding Proteins Genetic Predisposition to Disease Genome-Wide Association Study Glioma - genetics Humans Intracellular Signaling Peptides and Proteins Nerve Tissue Proteins Polymorphism, Single Nucleotide Transcription Factors - genetics Transcription Factors - metabolism |
Title | Functional analysis of low-grade glioma genetic variants predicts key target genes and transcription factors |
URI | https://www.ncbi.nlm.nih.gov/pubmed/33130899 https://pubmed.ncbi.nlm.nih.gov/PMC8041333 |
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