Genetic Association Analysis of Known Thoracic Aortic Aneurysm and Dissection Susceptibility Genes in a Han-Taiwanese Population

Thoracic aortic aneurysm and dissection (TAAD) is a fatal disease and has genetic heritability. Identifying associated loci of heritable thoracic aortic disease is therefore crucial for early screening and preventive surgery. We conducted a two-step single-center-based genome-wide association study to evaluate the genetic association of TAAD in Han-Taiwanese population. 91 patients with TAAD and 910 gender-matched controls were identified. In the first step, WDR36 and PPP4R1, which have not previously been reported to be associated with TAAD in human studies, exceeded the genome-wide significance threshold. In the second step, we focused our analysis on the previously reported TAAD-related genes to assess their associated risks in our population. Three genes with seven different single nucleotide polymorphism (SNP)s were found to be significant, including COL5A2, PRKG1 and SMAD4. Among these seven SNPs, the minor allele frequency of rs994493314, rs1195959339, rs375518580, rs1054669161 and rs1006794099 were lower than 1% in Han-Taiwanese population but extremely rare in the general population, supporting the potential differences in allele frequencies across populations. The result of this study provides additional insights into the genetic associations of TAAD in the Han-Taiwanese population and helps address the existing knowledge gap.