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Comprehensive funct...
Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma
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- Qin, Na (author)
- Nanjing Medical University
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- Li, Yuancheng (author)
- Nanjing Medical University
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- Wang, Cheng (author)
- Nanjing Medical University
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- Zhu, Meng (author)
- Nanjing Medical University
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- Dai, Juncheng (author)
- Nanjing Medical University
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- Hong, Tongtong (author)
- Nanjing Medical University
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- Albanes, Demetrius (author)
- National Cancer Institute, USA
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- Lam, Stephen (author)
- British Columbia Cancer Agency
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- Tardon, Adonina (author)
- University of Oviedo
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- Chen, Chu (author)
- Fred Hutchinson Cancer Research Center,Vanderbilt University,Harvard University,Nanjing Medical University
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- Goodman, Gary (author)
- Swedish Medical Center
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- Bojesen, Stig E. (author)
- Copenhagen University Hospital
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- Landi, Maria Teresa (author)
- National Cancer Institute, USA
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- Johansson, Mattias (author)
- International Agency for Research on Cancer, World Health Organization
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- Risch, Angela (author)
- University of Salzburg
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- Wichmann, H-Erich (author)
- World Orthopaedic Concern
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- Bickeboller, Heike (author)
- University Medical Center Göttingen
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- Rennert, Gadi (author)
- Technion - Israel Institute of Technology
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- Arnold, Susanne (author)
- University of Kentucky Medical Center
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- Brennan, Paul (author)
- International Agency for Research on Cancer, World Health Organization
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- Field, John K. (author)
- University of Liverpool
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- Shete, Sanjay (author)
- University of Texas MD Anderson Cancer Center
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- Le Marchand, Loic (author)
- University of Hawaii at Manoa
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- Melander, Olle (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Cardiovascular Research - Hypertension,Lund University Research Groups
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- Brunnstrom, Hans (author)
- Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Liu, Geoffrey (author)
- Princess Margaret Hospital University of Toronto
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- Hung, Rayjean J. (author)
- Sinai Health System
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- Andrew, Angeline (author)
- Dartmouth-Hitchcock Medical Center,Radboud University Nijmegen
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Kiemeney, Lambertus A. (author)
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- Zienolddiny, Shan (author)
- National Institute of Occupational Health, Norway
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- Grankvist, Kjell (author)
- Umeå University,Umeå universitet,Klinisk kemi
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- Johansson, Mikael (author)
- Umeå University,Umeå universitet,Onkologi
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- Caporaso, Neil (author)
- National Cancer Institute, USA
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- Woll, Penella (author)
- University of Sheffield
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- Lazarus, Philip (author)
- Washington State University
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- Schabath, Matthew B. (author)
- H. Lee Moffitt Cancer Center & Research Institute
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Aldrich, Melinda C. (author)
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- Stevens, Victoria L. (author)
- American Cancer Society
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- Jin, Guangfu (author)
- Nanjing Medical University
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Christiani, David C. (author)
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- Hu, Zhibin (author)
- Nanjing Medical University
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- Amos, Christopher I. (author)
- Baylor College of Medicine
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- Ma, Hongxia (author)
- Nanjing Medical University
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- Shen, Hongbing (author)
- Nanjing Medical University
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(creator_code:org_t)
- 2020-09-05
- 2021
- English.
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In: Frontiers of Medicine. - : Springer-Verlag New York. - 2095-0217 .- 2095-0225. ; 15:2, s. 275-291
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https://eprints.whit...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- 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 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 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 gene-based 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 well-studied 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- lung cancer
- genome-wide association study
- function annotation
- immune
- homologous recombination repair deficiency
- genetic heterogeneity
- function annotation
- genetic heterogeneity
- genome-wide association study
- homologous recombination repair deficiency
- immune
- lung cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Qin, Na
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Li, Yuancheng
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Wang, Cheng
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Zhu, Meng
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Dai, Juncheng
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Hong, Tongtong
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show more...
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Albanes, Demetri ...
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Lam, Stephen
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Tardon, Adonina
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Chen, Chu
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Goodman, Gary
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Bojesen, Stig E.
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Landi, Maria Ter ...
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Johansson, Matti ...
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Risch, Angela
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Wichmann, H-Eric ...
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Bickeboller, Hei ...
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Rennert, Gadi
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Arnold, Susanne
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Brennan, Paul
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Field, John K.
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Shete, Sanjay
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Le Marchand, Loi ...
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Melander, Olle
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Brunnstrom, Hans
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Liu, Geoffrey
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Hung, Rayjean J.
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Andrew, Angeline
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Kiemeney, Lamber ...
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Zienolddiny, Sha ...
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Grankvist, Kjell
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Johansson, Mikae ...
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Caporaso, Neil
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Woll, Penella
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Lazarus, Philip
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Schabath, Matthe ...
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Aldrich, Melinda ...
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Stevens, Victori ...
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Jin, Guangfu
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Christiani, Davi ...
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Hu, Zhibin
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Amos, Christophe ...
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Ma, Hongxia
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Shen, Hongbing
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Frontiers of Med ...
- By the university
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Umeå University
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Lund University