Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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Functional annotation of lung cancer-associated genetic variants by cell type-specific epigenome and long-range chromatin interactome

  • Lee, Andrew J. (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Jung, Inkyung (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
  • Received : 2020.12.03
  • Accepted : 2021.01.25
  • Published : 2021.03.31
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Abstract

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer-associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type-specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer-associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

Keywords

Acknowledgement

This work was supported by the Ministry of Science and ICT through the National Research Foundation in Republic of Korea under grant number NRF-2020R1A2C4001464 to IJ. A portion of the data used for this study was obtained from the Genome-InfraNet (IDs: 1711056526 and 1711065396) of the Korean Bioinformation Center.

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