Open AccessLeveraging cell-type-specific regulatory networks to interpret genetic variants in abdominal aortic aneurysm
Author(s) -
Shuping Ma,
Xi Chen,
Xiang Zhu,
Philip S. Tsao,
Wing Hung Wong
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2115601119
Subject(s) - biology , cell type , gene , disease , cell , genetics , abdominal aortic aneurysm , gene regulatory network , computational biology , gene expression , aneurysm , pathology , medicine , surgery
Significance Abdominal aortic aneurysm (AAA) is a common and severe disease with major genetic risk factors. In this study we generated enhancer-promoter contact data to identify regulatory elements in AAA-relevant cell types and identified changes in their predicted chromatin accessibility between AAA patients and controls. We integrated this information with disease-associated variants in regulatory elements and gene bodies to further understand the etiology and pathogenetic mechanisms of AAA. Our study combined whole-genome sequencing data with gene regulatory relations in disease-relevant cell types to reveal the important roles of the interleukin 6 pathway andERG andKLF regulation in AAA pathogenesis.