3.2 First Genome-Wide Association Study of Cardiovascular Magnetic Resonance Derived Aortic Distensibility Reveals 7 Loci

DOI

10.2991/artres.k.191224.015How to use a DOI?

Abstract

Background: Although arterial stiffness has demonstrated moderate heritability, our knowledge of the genes modulating arterial stiffness is still limited. We conducted genome-wide association studies (GWASs) of aortic distensibility (AoD) in both ascending (AA) and proximal descending aorta (PDA) to discover novel genetic loci.

Methods: Our study included ~14,500 European-ancestry participants in the UK Biobank study. AoD in AA and PDA were assessed at the level of pulmonary artery bifurcation using transverse cine images obtained from 1.5 Tesla cardiovascular magnetic resonance scanners1. Relative cross-sectional aortic area change was calculated using an automated tool2. GWASs were performed in a discovery cohort (n = 3,841), with replication in 9,630 individuals. We also performed GWASs for each trait in the combined cohort (n = 14,596). All GWASs were performed under a linear mixed model and adjusted for age, sex, height, weight, systolic blood pressure, diabetes, smoking, genotype array type and the first ten principal components.

Results: We found three significant loci (p < 5 × 10^–8) for AA AoD and six for PDA AoD (Figure 1A). The ELN locus was discovered and replicated for AA AoD, and was significantly associated with PDA AoD in the combined cohort (Figure 1B). ELN encodes elastin a central component of elastic fibres in the heart and blood vessels. The most significant locus for PDA AoD was FBLN5; FBLN5 encodes fibulin 5 which is vital for elastic fibre formation.

Conclusions: In the first GWAS of AoD, we discovered seven unique loci. These results enhance our understanding of the biological processes underlying arterial stiffness.

Figure 1A

Venn diagram of the 7 genome-wide significant loci from our study

Figure 1B

Miami plot of distensibility in the ascending (AA) and proximal descending aorta (PDA) in the combined cohort. Quartered cross symbol denotes locus was also genome-wide significant in discovery and replication cohorts.

Copyright

© 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

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TY  - JOUR
AU  - Kenneth Fung
AU  - Luca Biasiolli
AU  - Evan Hann
AU  - Julia Ramirez
AU  - Elena Lukaschuk
AU  - Nay Aung
AU  - Jose Paiva
AU  - Konrad Werys
AU  - Mihir Sanghvi
AU  - Ross Thomson
AU  - Jennifer Rayner
AU  - Henrike Puchta
AU  - Niall Moon
AU  - Katharine Thomas
AU  - Aaron Lee
AU  - Stefan Piechnik
AU  - Stefan Neubauer
AU  - Steffen Petersen
AU  - Patricia Munroe
PY  - 2020
DA  - 2020/02/15
TI  - 3.2 First Genome-Wide Association Study of Cardiovascular Magnetic Resonance Derived Aortic Distensibility Reveals 7 Loci
JO  - Artery Research
SP  - S21
EP  - S22
VL  - 25
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191224.015
DO  - 10.2991/artres.k.191224.015
ID  - Fung2020
ER  -