Genomic insights in ascending aortic size and distensibility

Jan Walter Benjamins*, Ming Wai Yeung, Yordi J. van de Vegte, M. Abdullah Said, Thijs van der Linden, Daan Ties, Luis E. Juarez-Orozco, Niek Verweij, Pim van der Harst

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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Samenvatting

Background
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.

Methods
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.

Findings
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.

Interpretation
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.
Originele taal-2English
Artikelnummer103783
Aantal pagina's18
TijdschriftEBioMedicine
Volume75
Vroegere onlinedatum27-dec-2021
DOI's
StatusPublished - 3-jan-2022

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