Table 3. Radiogenomics studies on GTAAD.

Study	Objective	Study population	Results	Comments
Benjamins et al. (20)	Identify genetic loci that involved in mechanisms affecting AAo size and function in the general population	GWAS on up to 37,910 individuals from the UK Biobank using AAo maximum area, AAo minimum area and AAo distensibility	Total of 107 SNPs in 78 loci revealed a causal association with aneurysm development, but not with other vascular diseases were shown using Mendelian randomization analysis	Strength: the use of AI-approach to analyse large quantities of CMR-data, which subsequently allowed us to perform a GWAS on AAo size and function in the largest cohort to date
	Provide genetic evidence for their role in aortic aneurysm development			Weakness: unable to verify all images and predictions manually due to large sample size and quantity of images; unable to differentiate between syndromic, familial and sporadic occurrences of AAo enlargement in the current analyses
Pirruccello et al. (21)	Identify genetic loci associated with ascending and descending aortic diameter	UK Biobank, 43,000 participants with MRI	A total of 82 loci in ascending and 47 loci in descending thoracic aortic diameter were identified, there were 14 loci overlapped	Strength: illustrated the efficacy of deep learning in deriving quantitative phenotypes using raw signal data at a population level; demonstrate the use of quantitative traits study to have a better understanding on disease mechanism of aneurysm and dissection; a polygenic score was developed for ascending aortic size, which is an independent risk factor for aneurysmal development of aorta
			There was association between thoracic aortic aneurysm in 385,621 UK Biobank participants and polygenic score for ascending aortic diameter	Weakness: majority of the study population consisted of European-ancestry UK Biobank participants which limited the generalizability; the aortic measurements were derived using trained deep learning model using cardiologist-annotated segmentation data, however, majority of images were not manually reviewed
Miner et al. (22)	To identify the genetic causality and association on different morphologic subtype	126 AAA patients with normal descending thoracic aorta and 93 AAA patients with radiological features of thoracic aortic disease	The genetic pathways in double strain DNA break repair, variants in vitamin D signaling cholesterol metabolism and extracellular matrix breakdown were associated with AAA patients with thoracic aortic diseases	Strength: illustrated the use of next generation sequencing and CTA analysis for evaluating endo-phenotypes possibly related to the etiology of AAA
				Weakness: limited applicability as only patients with confirmed European ancestry were included to detect genetic variation; limited sample size; lack of tissue sample to evaluate the outcomes of the variants on transcription and translation
Francis et al. (23)	GWAS of aortic distensibility for aortic aneurysms and brain white matter hyperintensities	The GWAS of aortic distensibility and area from UK Biobank cardiac MRI data of up to 32,590 Caucasian population	A total of 102 loci (including 27 novel associations) related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases were identified	Strength: a significant heritable component was shown from large-scale studies in GWAS of ascending and descending aortic distensibility; the evidence of mechanistic associations of TGF-β, IGF, PDGF and VEGF signaling pathways with aortic distensibility were shown
			Four signaling pathways (TGF-β, IGF, VEGF and PDGF) associated with aortic distensibility were found using functional analysis	Weakness: only Caucasian individuals from UK Biobank were included, which was not representative of the whole UK population; the use of non-invasive blood pressure as proxies for central blood pressure measurement might affect the accuracy of the distensibility calculations

GTAAD, genetically triggered thoracic aortic aneurysm and dissection; AAA, abdominal aortic aneurysm; AAo, ascending aorta; AI, artificial intelligence; CMR, cardiovascular magnetic resonance; CTA, computed tomography angiogram; GWAS, genome-wide association studies; IGF, insulin-like growth factor; MRI, magnetic resonance imaging; PDGF, platelet-derived growth factor; SNPs, single nucleotide polymorphisms; TGF-β, transforming growth factor β; VEGF, vascular endothelial growth factor.