Genome-wide association analysis of pulse wave velocity traits provide new insights into the causal relationship between arterial stiffness and blood pressure

Abstract:

Background The pathophysiology of arterial stiffness is not completely understood. Pulse wave velocity (PWV) is an established marker for arterial stiffness. We compare genetics of three PWV modes, namely carotid-femoral PWV (cfPWV), brachial-ankle (baPWV) and brachial-femoral (bfPWV), reflecting different vascular segments to analyse association with genetic variants, heritability and genetic correlation with other biological traits. Furthermore we searched for shared genetic architecture concerning PWV, blood pressure (BP) and coronary artery disease (CAD) and examined the causal relationship between PWV and BP.

Methods and results We performed a genome-wide association study (GWAS) for cfPWV, baPWV and bfPWV in LIFE-Adult (N = 3,643–6,734). We analysed the overlap of detected genetic loci with those of BP and CAD and performed genetic correlation analyses. By bidirectional Mendelian Randomization, we assessed the causal relationships between PWV and BP. For cfPWV we identified a new locus with genome-wide significance near SLC4A7 on cytoband 3p24.1 (lead SNP rs939834: p = 2.05x10-8). We replicated a known PWV locus on cytoband 14q32.2 near RP11-61O1.1 (lead SNPs: rs17773233, p = 1.38x10-4; rs1381289, p = 1.91x10-4) For baPWV we estimated a heritability of 28% and significant genetic correlation with hypertension (rg = 0.27, p = 6.65x10-8). We showed a positive causal effect of systolic blood pressure on PWV modes (cfPWV: p = 1.51x10-4; bfPWV: p = 1.45x10-3; baPWV: p = 6.82x10-15).

Conclusions We identified a new locus for arterial stiffness and successfully replicated an earlier proposed locus. PWV shares common genetic architecture with BP and CAD. BP causally affects PWV. Larger studies are required to further unravel the genetic determinants and effects of PWV.

DOI: 10.1371/journal.pone.0237237

Projects: LIFE Adult

Publication type: Journal article

Journal: PLOS ONE

Editors: Kathrin Eller

Human Diseases: Arteriosclerosis, Arteriosclerotic cardiovascular disease

Citation: PLoS ONE 15(8):e0237237

Date Published: 13th Aug 2020

Registered Mode: by DOI

Authors: Michael Rode, Andrej Teren, Kerstin Wirkner, Katrin Horn, Holger Kirsten, Markus Loeffler, Markus Scholz, Janne Pott

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Rode, M., Teren, A., Wirkner, K., Horn, K., Kirsten, H., Loeffler, M., Scholz, M., & Pott, J. (2020). Genome-wide association analysis of pulse wave velocity traits provide new insights into the causal relationship between arterial stiffness and blood pressure. In K. Eller (Ed.), PLOS ONE (Vol. 15, Issue 8, p. e0237237). Public Library of Science (PLoS). https://doi.org/10.1371/journal.pone.0237237
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Created: 16th Aug 2020 at 05:35

Last updated: 7th Dec 2021 at 17:58

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