The TAGA Study: A Study of Factors Determining Aortic Diameter in Families at High Risk of Abdominal Aortic Aneurysm Reveal Two New Candidate Genes

Abstract

A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A Genomic Analysis (TAGA) study comprises 407 individuals related in 12 families. Each family was collected through a proband with AAA. We calculated heritability and genetic correlations between abdominal aortic diameter and clinical parameters. A genome-wide linkage scan was performed based on 4.6 million variants. A predictive model was calculated with conditional forest. Heritability of the abdominal aortic diameter was 34%. Old age, male sex, higher height, weight, creatinine levels in serum, and better lung capacity were the best predictors of aortic diameter. Linkage analyses suggested the implication of Epidermal Growth Factor Receptor (EGFR) and Betacellulin (BTC) genes with aortic diameter. This is the first study to evaluate genetic components of variation of the aortic diameter in a population of AAA high-risk individuals. These results reveal EGFR, a gene that had been previously implicated in AAA, as a determinant of aortic diameter variation in healthy genetically enriched individuals, and might indicate that a common genetic background could determine the diameter of the aorta and future risk of AAA.