Potential association of genetic variants with thoracic aortic aneurysm and dissection: Evidence from a Japanese community-based cohort.

Authors

Kentaro Akabane, Ken Nakamura, Hidenori Sato, Tsuneo Konta, Shusuke Arai, Yasushi Imai, Tetsuro Uchida

Published in

General thoracic and cardiovascular surgery. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition for which early risk stratification and preventive strategies present critical challenges. Although genetic contributions are well established in high-risk populations, the clinical relevance of rare variants in the general population remains poorly understood. We aimed to explore the association between low-frequency homozygous minor allele genotypes in TAAD-related genes and TAAD-related mortality using a Japanese community-based cohort.
We selected 14 single-nucleotide polymorphisms from genes with definitive or strong clinical validity for TAAD, based on the criterion that the frequency of individuals homozygous for the minor allele was less than 5%. Participants with any low-frequency homozygous minor allele genotypes were classified as carriers, while those without such genotypes were classified as non-carriers. The primary outcome was TAAD-related mortality, and we examined whether carrier status was associated with the risk of TAAD-related death.
Among 24,478 participants, we analyzed 5,722 individuals (1,499 carriers and 4,223 non-carriers) who had genome-wide genotyping data. TAAD-related deaths were observed in 12 individuals (8 carriers and 4 non-carriers). Carriers exhibited lower survival rates compared to non-carriers. Univariate Cox model analysis showed carrier status was associated with increased TAAD-related mortality. These variants had not been previously classified as pathogenic.
Low-frequency homozygous minor allele genotypes in established TAAD-related genes were associated with TAAD-related mortality in a general Japanese population. These findings should be interpreted as hypothesis-generating and are limited to mortality as the endpoint, providing population-based epidemiological evidence on the potential clinical relevance of currently unclassified variants.

PMID:
42467302
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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