孟德尔随机化
全基因组关联研究
升主动脉
候选基因
单核苷酸多态性
冠状动脉疾病
人口
生物
遗传关联
生物信息学
遗传学
医学
内科学
主动脉
基因
遗传变异
基因型
环境卫生
作者
Jan W. Benjamins,Ming Wai Yeung,Yordi J. van de Vegte,M. Abdullah Said,Thijs van der Linden,Daan Ties,Luis Eduardo Juárez-Orozco,Niek Verweij
出处
期刊:EBioMedicine
[Elsevier]
日期:2022-01-01
卷期号:75: 103783-103783
被引量:22
标识
DOI:10.1016/j.ebiom.2021.103783
摘要
Alterations in the anatomic and biomechanical properties of the ascending aorta (AAo) can give rise to various vascular pathologies. The aim of the current study is to gain additional insights in the biology of the AAo size and function.We developed an AI based analysis pipeline for the segmentation of the AAo, and the extraction of AAO parameters. We then performed genome-wide association studies of AAo maximum area, AAo minimum area and AAo distensibility in up to 37,910 individuals from the UK Biobank. Variants that were significantly associated with AAo phenotypes were used as instrumental variables in Mendelian randomization analyses to investigate potential causal relationships with coronary artery disease, myocardial infarction, stroke and aneurysms.Genome-wide association studies revealed a total of 107 SNPs in 78 loci. We annotated 101 candidate genes involved in various biological processes, including connective tissue development (THSD4 and COL6A3). Mendelian randomization analyses showed a causal association with aneurysm development, but not with other vascular diseases.We identified 78 loci that provide insights into mechanisms underlying AAo size and function in the general population and provide genetic evidence for their role in aortic aneurysm development.
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