Language
English
Publication Date
9-1-2024
Journal
American Journal of Medical Genetics Part A
DOI
10.1002/ajmg.a.63644
PMID
38688863
PMCID
PMC11315632
PubMedCentral® Posted Date
9-1-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
The male predominance in sporadic thoracic aortic aneurysm and dissection (TAD) suggests that the X chromosome contributes to TAD, but this has not been tested. We investigated whether X-linked variation-common (minor allele frequency [MAF] ≥0.01) and rare (MAF < 0.01)-was associated with sporadic TAD in three cohorts of European descent (Discovery: 364 cases, 874 controls; Replication: 516 cases, 440,131 controls, and ARIC [Atherosclerosis Risk in Communities study]: 753 cases, 2247 controls). For analysis of common variants, we applied a sex-stratified logistic regression model followed by a meta-analysis of sex-specific odds ratios. Furthermore, we conducted a meta-analysis of overlapping common variants between the Discovery and Replication cohorts. For analysis of rare variants, we used a sex-stratified optimized sequence kernel association test model. Common variants results showed no statistically significant findings in the Discovery cohort. An intergenic common variant near SPANXN1 was statistically significant in the Replication cohort (p = 1.81 × 10-8). The highest signal from the meta-analysis of the Discovery and Replication cohorts was a ZNF182 intronic common variant (p = 3.5 × 10-6). In rare variants results, RTL9 reached statistical significance (p = 5.15 × 10-5). Although most of our results were statistically insignificant, our analysis is the most comprehensive X-chromosome association analysis of sporadic TAD to date.
Keywords
Aged, Female, Humans, Male, Middle Aged, Aortic Aneurysm, Thoracic, Case-Control Studies, Chromosomes, Human, X, Cohort Studies, Dissection, Thoracic Aorta, Gene Frequency, Genes, X-Linked, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Published Open-Access
yes
Recommended Citation
Musfee, Fadi I; Jun, Goo; Mitchell, Laura E; et al., "X-Linked Genetic Associations in Sporadic Thoracic Aortic Dissection" (2024). Faculty and Staff Publications. 4253.
https://digitalcommons.library.tmc.edu/baylor_docs/4253