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| 1 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. | Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 2 | Biomimetic oxidation of nonphenolic lignin models by Mn(III): New observations on the oxidizability of guaiacyl and syringyl substructures显示文摘 | Hammel KE Tardone PJ Moen MA | 1989 | Archives of Biochemistry and Biophysics1989，270，1： | 1 |
| 3 | The oxidative 4-dechlorination of polychlorinated phenols is catalyzed by extracellular fungal lignin peroxidases显示文摘 | Hammel K E Tardone P J | 1988 | Biochemistry1988，27，： | 1 |
| 4 | Chronic helminth infection and helminth - derived egg antigens promote adipose tissue M2 macrophages and improve insulin sensitivity in obese mice 显示文摘 | Hussaarts L Garcfa - Tardon N Van Beek L | 2015 | FASEB journal : official publication of the Federation of American Societies for Experimental Biology2015，29，7： | 1 |
| 5 | Leisure-time physical activity and lung cancer: a meta-analysis显示文摘 | Adonina Tardon Won Jin Lee Miguel Delgado-Rodriguez Mustafa Dosemeci Demetrius Albanes Robert Hoover Aaron Blair | 2005 | Cancer Causes & Control2005，，： | 1 |
| 6 | Lung cancer risk in iron and steel foundry workers:a nested case control study in Asturias,Spain显示文摘 | RODRIGUEZ V TARDON A KOGEVINAS M | 2000 | Am J Ind Med2000，38，6： | 1 |
| 7 | Lignin degradation and lignin peroxidase production in cultures of Phanerochaete chrysosporium immobilized on porous ceramic supports 显示文摘 | Cornwell K Tinland-Butez M Tardone P J | 1990 | Enzyme Microb Technol1990，12，1： | 1 |
| 8 | Leisure-time physical activity and lung cancer: a meta-analysis显示文摘 | Tardon A Lee WJ Delgado-Rodriguez M | 2005 | Cancer Causes Contr2005，16，4： | 1 |
| 9 | Leisure-time physical activity and lung cancer:a meta-analysis显示文摘 | Tardon A Lee WJ Delgado-Rodriguez M | 2005 | Cancer Causes Control2005，16，4： | 1 |
| 10 | SiPTH: Singing transcription based on hysteresis defined on the pitch-time curve显示文摘 | MOLINA E TARDON L J BARBANCHO A M | 2015 | IEEE/ACM Transactions on Audio Speech and Language Processing2015，23，2： | 1 |
| 11 | The oxidative 4-dechlorination of polychlorinated phenols is catalyzed by extracellular fungal lignin peroxidases 显示文摘 | HAMMEL K E TARDONE P J | 1988 | Biochemistry1988，27，12： | 1 |
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