TABLE 1.

Increased Burden of Rare VUSs and Rare Missense VUSs in the ESTAD Cases

	ESTAD-EA (n = 231)	ESP-EA (n = 4,300)	OR (95% CI)	p Value
VUSs in ESTAD-EA versus ESP-EA
HTAD genes VUSs	74	712	2.42 (1.78–3.17)	2.0 × 10−8
HTAD genes missense VUSs	70	708	2.21 (1.65–2.95)	3.9 × 10−7
HTAD genes synonymous variants*	40	839	0.86 (0.61–1.23)	0.44
HCM genes VUSs†	23	350	0.80 (0.51–1.25)	0.33
VUSs in HTAD genes in ESTAD-EA versus ESP-EA
ACTA2	2	2	18.77 (2.63–133.85)	0.01
TGFBR2	7	10	13.41 (5.06–35.55)	1.0 × 10−5
TGFBR1	7	32	4.17 (1.82–9.55)	3.1 × 10−3
LOX	3	19	2.97 (0.87–10.09)	0.10
MYLK	8	54	2.82 (1.33–6.00)	0.01
SMAD3	1	7	2.67 (0.33–21.76)	0.34
COL3A1	12	112	2.05 (1.11–3.77)	0.03
TGFB2	6	58	1.95 (0.83–4.57)	0.14
MYH11	18	233	1.48 (0.90–2.43)	0.14
FBN1	10	183	1.02 (0.53–1.95)	0.87

Values are the number of rare variants in genes grouped together (top section) or genes individually (lower section), unless otherwise indicated.

^*Synonymous variants do not alter amino acid sequence.

^†HCM genes.

CI = confidence interval; EA = European ancestry; ESP = Exome Sequencing Project; ESTAD = early onset of sporadic thoracic aortic dissection; HCM = hypertrophic cardiomyopathy; HTAD = heritable thoracic aortic disease; OR = odds ratio; VUSs = variants of unknown significance.