X-linked genetic associations in sporadic thoracic aortic dissection.

Autor: Musfee FI; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.; Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., Jun G; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Mitchell LE; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Chen H; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Guo D; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA., Prakash SK; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA., Adkar SS; Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Grove ML; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Choi RB; Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Klarin D; Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.; Department of Surgery, Stanford University School of Medicine, Palo Alto, California, USA., Boerwinkle E; Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA., Milewicz DM; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Sep; Vol. 194 (9), pp. e63644. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1002/ajmg.a.63644
Abstrakt: 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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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