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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.

SUBMITTER: Rode M

PROVIDER: S-EPMC7425880 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Rode Michael M Teren Andrej A Wirkner Kerstin K Horn Katrin K Kirsten Holger H Loeffler Markus M Scholz Markus M Pott Janne J

PloS one 20200813 8

<h4>Background</h4>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 architectu ...[more]

PMID: 32790701

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Project description:Background:Obesity is an important risk factor of cardiovascular disease (CVD). Atherosclerosis can be considered an important signal of CVD. Primary physicians can reduce the risk of CVD by preventing and treating obesity. Therefore, finding a tool to diagnose the association of obesity with arteriosclerosis is important. The association between obesity parameters and arterial stiffness remains controversial. To our knowledge, no previous studies reported the relationships between multiple new anthropometric parameters (a body shape index [ABSI], body round index [BRI], and visceral adiposity index [VAI]) and brachial-ankle wave velocity (ba-PWV) as an indicator of CVD risk, especially in the Korean population. Objective:To investigate the relationships between arterial stiffness (assessed using ba-PWV) and anthropometric parameters estimated on the basis of body mass index (BMI), waist circumference (WC), ABSI, BRI, and VAI, and to identify the indicators of obesity that best represents CVD risk. Methods:A total of 2,647 adults (1,474 men and 1,173 women) were recruited for this cross-sectional study. The correlations between the anthropometric indexes (BMI, WC, ABSI, BRI, and VAI) and mean ba-PWV were analyzed. A multivariate linear regression analysis was performed to evaluate the association between each anthropometric and the presence of arterial stiffness. Results:We investigated the relationships between the obesity parameters and ba-PWV by adjusting the covariates (age, diabetes mellitus [DM], hypertension [HTN], and smoking status) related to the mean ba-PWV. In the multivariate regression analysis, ABSI (men: ? =0.066, p<0.01; women: ? =0.087, p<0.001) and VAI (men: ? =0.067, p<0.01; women: ? =0.136, p<0.001) were found to be significantly correlated with the mean ba-PWV in both men and women in Korea. Conclusion:Among the new obesity indices, ABSI and VAI were found to be significantly associated with arterial stiffness, represented by the mean ba-PWV, in both men and women in Korea. These results suggest that ABSI and VAI may be convenient, highly cost-effective, and simple assessment tools for obesity and CVD risk in clinical practice.

Project description:IntroductionIntestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness.Methods and analysisAn observational case-control study will be developed. Cases will be defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), Cardio-Ankle Vascular Index (CAVI), brachial ankle pulse wave velocity (ba or ba-PWV) above the 90th percentile, for age and sex, of the reference population. Controls will be selected from the same population as cases. The study will be developed in Primary Healthcare Centres. We will select 500 subjects (250 cases and 250 controls), between 45 and 74 years of age. Cases will be selected from a database that combines data from EVA study (Spain) and Guimarães/Vizela study (Portugal).Measurementscf-PWV will be measured using the SphygmoCor system, CAVI, ba-PWV and Ankle-Brachial Index will be determined using VaSera device. Gut microbiome composition in faecal samples will be determined by 16S ribosomal RNA sequencing. Lifestyle will be assessed by food frequency questionnaire, adherence to the Mediterranean diet and IPAQ (International Physical Activity Questionnaire). Body composition will be evaluated by bioimpedance.Ethics and disseminationThe study has been approved by 'Committee of ethics of research with medicines of the health area of Salamanca' on 14 December 2018 (cod. 2018-11-136) and the 'Ethics committee for health of Guimaraes' (Portugal) on 15 October 2019 (ref: 67/2019). All study participants will sign an informed consent form agreeing to participate in the study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow a better description of gut microbiota in patients with arterial stiffness.Trial registration detailsClinicalTrials.gov, identifier NCT03900338.

Dataset Information

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

Publications

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

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