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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 | Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients显示文摘 | Ouattara A Lecomte P Le Manach Y Landi M | | 0，，04： | 1 |
| 3 | Comparative cardiac effects of terlipressin vasopressin, and norepine- phrine on an isolated perfused rabbit heart 显示文摘 | Ouattara A Landi M Le Manach Y | 2005 | Anesthesiology2005，102，1： | 1 |
| 4 | Selective small molecule stat3 inhibitor reduces breast cancer tumor-initiating cells and improves recurrence free survival in a human-xenograt model 显示文摘 | Dave B Landis MD Dobroleeki LE | 2012 | PLoS One2012，7，30： | 1 |
| 5 | Changing Indication for CS:a 38-year experience at a community hospital显示文摘 | Hadded H Landy LE | 1978 | Obstet gynecol1978，51，2： | 1 |
| 6 | Role of tachykinins in castor oil induced disrrhoea in rats显示文摘 | Croci T Landi M Elmonds-Alt X Le Fur G Maffrand JP Manara L | 1997 | Br J Pharmacol1997，121，： | 1 |
| 7 | Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients显示文摘 | Alexandre Ouattara Patrick Lecomte Yannick Le Manach Marc Landi Sophie Jacqueminet Igor Platonov Nicolas Bonnet Bruno Riou Pierre Coriat | 2005 | Anesthesiology2005，，4： | 1 |
| 8 | Changing indication for CS:38-year experience at a community hospital显示文摘 | Haddad H Landy LE | 1978 | Orstetr Gynecot1978，51，2： | 1 |
| 9 | Changing indication for CS:38-year experience at a community hospital显示文摘 | Haddad H Landy LE | 1978 | Orstetr Gynecot1978，51，2： | 1 |
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