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Context-aware single-cell multiomics approach identifies cell-type-specific lung cancer susceptibility genes.
Long, Erping; Yin, Jinhu; Shin, Ju Hye; Li, Yuyan; Li, Bolun; Kane, Alexander; Patel, Harsh; Sun, Xinti; Wang, Cong; Luong, Thong; Xia, Jun; Han, Younghun; Byun, Jinyoung; Zhang, Tongwu; Zhao, Wei; Landi, Maria Teresa; Rothman, Nathaniel; Lan, Qing; Chang, Yoon Soo; Yu, Fulong; Amos, Christopher I; Shi, Jianxin; Lee, Jin Gu; Kim, Eun Young; Choi, Jiyeon.
Afiliación
  • Long E; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Yin J; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Shin JH; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Li Y; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Li B; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Kane A; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Patel H; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Sun X; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Wang C; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Luong T; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Xia J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Han Y; Department of Biomedical Sciences, Creighton University, Omaha, NE, USA.
  • Byun J; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Zhang T; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Zhao W; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Landi MT; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Rothman N; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Lan Q; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Chang YS; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Yu F; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • Amos CI; Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, China.
  • Shi J; Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
  • Lee JG; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Kim EY; Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. CSJGLEE@yuhs.ac.
  • Choi J; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. narae97@yuhs.ac.
Nat Commun ; 15(1): 7995, 2024 Sep 12.
Article en En | MEDLINE | ID: mdl-39266564
ABSTRACT
Genome-wide association studies (GWAS) identified over fifty loci associated with lung cancer risk. However, underlying mechanisms and target genes are largely unknown, as most risk-associated variants might regulate gene expression in a context-specific manner. Here, we generate a barcode-shared transcriptome and chromatin accessibility map of 117,911 human lung cells from age/sex-matched ever- and never-smokers to profile context-specific gene regulation. Identified candidate cis-regulatory elements (cCREs) are largely cell type-specific, with 37% detected in one cell type. Colocalization of lung cancer candidate causal variants (CCVs) with these cCREs combined with transcription factor footprinting prioritize the variants for 68% of the GWAS loci. CCV-colocalization and trait relevance score indicate that epithelial and immune cell categories, including rare cell types, contribute to lung cancer susceptibility the most. A multi-level cCRE-gene linking system identifies candidate susceptibility genes from 57% of the loci, where most loci display cell-category-specific target genes, suggesting context-specific susceptibility gene function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Estudio de Asociación del Genoma Completo / Análisis de la Célula Individual / Neoplasias Pulmonares Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Estudio de Asociación del Genoma Completo / Análisis de la Célula Individual / Neoplasias Pulmonares Límite: Female / Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido