Genomics Inform.  2021 Mar;19(1):e3. 10.5808/gi.20073.

Functional annotation of lung cancer‒associated genetic variants by cell type‒specific epigenome and long-range chromatin interactome

• Lee AJ
• Jung I

• KMID: 2514707
• DOI: http://doi.org/10.5808/gi.20073

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.

Keyword

3D chromatin interaction; -regulatory element; genome-wide association study; lung cancer; single-cell RNA sequencing; single nucleotide polymorphism