scholarly journals Genetic Architecture of Quantitative Cardiovascular Traits: Blood Pressure, ECG and Imaging Phenotypes

2020 ◽  
Author(s):  
Nay Aung ◽  
William Young ◽  
Stefan Van Duijvenboden ◽  
Julia Ramírez ◽  
Steffen Petersen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Architecture ◽  
Cardiovascular Traits

Relationship between alcohol use, blood pressure and hypertension: an association study and a Mendelian randomisation study

2019 ◽  
Vol 73 (9) ◽  
pp. 796-801 ◽  
Author(s):  
Pian-Pian Zhao ◽  
Liang-Wen Xu ◽  
Tao Sun ◽  
Yin-Yin Wu ◽  
Xiao-Wei Zhu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Alcohol Use ◽  
Allele Frequency ◽  
Alcohol Drinking ◽  
Chinese Culture ◽  
Causal Effect ◽  
Strong Relationship ◽  
Mendelian Randomisation ◽  
Cardiovascular Traits ◽  
Pooled Samples

BackgroundPast studies have found a strong relationship between alcohol drinking and human health.MethodsIn this study, we first tested the association of rs671 with alcohol use in 2349 participants in southeast China. We then evaluated the causal impact between alcohol use and cardiovascular traits through a Mendelian randomisation (MR) analysis.ResultsWe found strong evidence for the association of rs671 in the ALDH2 gene with alcohol drinking (p=6.08×10-47; ORadj G=4.50, 95% CI 3.67 to 5.52). We found that female G carriers of rs671 had a higher proportion of non-drinkers than male G carriers (88.01% vs 38.70%). In non-drinkers, the female G allele frequency was higher than the male G allele frequency (71.1% vs 55.2%). MR analysis suggested that alcohol use had a causal effect on blood pressure (increasing 9.46 mm Hg for systolic blood pressure (p=9.67×10-4) and 7.50 mm Hg for diastolic blood pressure (p=9.62×10-5)), and on hypertension in men (p=0.011; OR =1.19, 95% CI 1.04 to 1.36) and in pooled samples (p=0.013; OR =1.20, 95% CI 1.04 to 1.39), but not in women. We did not observe a causal effect of alcohol use on body mass index and lipid levels; further studies are needed to clarify the non-causal relationship.ConclusionsCompared to never-drinkers, current and previous alcohol use had a causal effect on blood pressure and hypertension in pooled samples and in men. These results reflect Chinese culture which does not encourage women to drink.

The genetic architecture of blood pressure variation

2009 ◽  
Vol 3 (6) ◽  
pp. 418-425 ◽  
Author(s):  
Patricia B. Munroe ◽  
Toby Johnson ◽  
Mark J. Caulfield
Keyword(s):  
Blood Pressure ◽  
Genetic Architecture ◽  
Pressure Variation ◽  
Blood Pressure Variation

Abstract 15554: Mendelian Randomization of 436 Circulating Proteins Identifies Putatively Causal Proteins for Cardiovascular Disease and Its Risk Factors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Chen Yao ◽  
Shih-jen Hwang ◽  
Tianxiao Huan ◽  
Roby Joehanes ◽  
Daniel Levy
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Transcriptional Start Site ◽  
Fasting Blood Glucose ◽  
Clinical Biomarkers ◽  
Cardiovascular Traits

Introduction: Despite numerous efforts to understand the molecular mechanisms underlying cardiovascular disease, it remains the leading cause of death worldwide. Circulating proteins are frequently used as clinical biomarkers and may serve as effective drug targets. Hypothesis: Identifying genetic variants associated with circulating protein concentrations (pQTLs) and combining them with genome-wide association study (GWAS) results may bridge a knowledge gap of unexplained heritability, identify potentially causal proteins, and highlight promising therapeutic targets. Methods: We measured concentrations of 436 plasma proteins among 484 Framingham participants using OLINK cardiovascular disease and inflammation panels. For each protein, we conducted a GWAS using 1000G imputed genotypes (imputation quality >20%). Then we performed two sample Mendelian randomization using cis-pQTLs (SNPs within 1Mb of transcriptional start site of the protein coding gene) as instrumental variables and 11 public cardiovascular trait GWAS (coronary artery disease (CAD), HDL cholesterol, LDL cholesterol, triglycerides (TG), body mass index (BMI), obesity, fasting blood glucose, type 2 diabetes, systolic blood pressure, diastolic blood pressure, and Hypertension) as outcomes. Results: At Bonferroni-corrected P<0.05, we identified 5281 cis-pQTLs for 76 proteins. Mendelian randomization identified 13 putatively causal proteins for seven cardiovascular traits: FGF-5, IL-6RA, LPL , and TFPI for CAD; CAPG, IGG_FCrrec, LPL, and TFPI for HDL; KIM1, LPL, and TNFB for TG, ENTPD6 for BMI; FGF-5, TFPI, UMOD, IGFBP3, PXN, and NUCB2 for blood pressure traits. Conclusions: At Bonferroni-corrected P<0.05, we identified 5281 cis-pQTLs for 76 proteins. Mendelian randomization identified 13 putatively causal proteins for seven cardiovascular traits: FGF-5, IL-6RA, LPL , and TFPI for CAD; CAPG, IGG_FCrrec, LPL, and TFPI for HDL; KIM1, LPL, and TNFB for TG, ENTPD6 for BMI; FGF-5, TFPI, UMOD, IGFBP3, PXN, and NUCB2 for blood pressure traits.

scholarly journals Blood pressure and heart rate QTL in mice of the B6/D2 lineage: sex differences and environmental influences

2009 ◽  
Vol 36 (3) ◽  
pp. 158-166 ◽  
Author(s):  
David A. Blizard ◽  
Arimantas Lionikas ◽  
David J. Vandenbergh ◽  
Terrie Vasilopoulos ◽  
Glenn S. Gerhard ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Genetic Architecture ◽  
Interval Mapping ◽  
Adult Mice ◽  
Two Measures ◽  
Males And Females ◽  
Trait Locus ◽  
Sampling Procedures ◽  
Female Specific

A quantitative trait locus (QTL) approach was used to define the genetic architecture underlying variation in systolic blood pressure (SBP) and heart rate (HR), measured indirectly on seven occasions by the tail cuff procedure. The tests were conducted in 395 F2 adult mice (197 males, 198 females) derived from a cross of the C57BL/6J (B6) and DBA/2J (D2) strains and in 22 BXD recombinant-inbred (RI) strains. Interval mapping of F2 data for the first 5 days of measurement nominated one statistically significant and one suggestive QTL for SBP on chromosomes (Chr) 4 and 14, respectively, and two statistically significant QTL for HR on Chr 1 (which was specific to female mice) and Chr 5. New suggestive QTL emerged for SBP on Chr 3 (female-specific) and 8 and for HR on Chr 11 for measurements recorded several weeks after mice had undergone stressful blood sampling procedures. The two statistically significant HR QTL were confirmed by analyses of BXD RI strain means. Male and female F2 mice did not differ in SBP or HR but RI strain analyses showed pronounced strain-by-sex interactions and a negative genetic correlation between the two measures in both sexes. Evidence for a role for mitochondrial DNA was found for both HR and SBP. QTL for HR and SBP may differ in males and females and may be sensitive to different environmental contexts.

scholarly journals Homogeneous Assay of rs4343, anACEI/D Proxy, and an Analysis in the British Women’s Heart and Health Study (BWHHS)

2008 ◽  
Vol 24 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Mohammad Reza Abdollahi ◽  
Shuwen Huang ◽  
Santiago Rodriguez ◽  
Philip Alexander Isles Guthrie ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Linkage Disequilibrium ◽  
Liquid Phase ◽  
Diastolic Blood Pressure ◽  
Current Literature ◽  
Health Study ◽  
Insertion And Deletion ◽  
Homogeneous Assay ◽  
Post Hoc ◽  
Cardiovascular Traits

Current literature suggests thatACESNP rs4343,ACE2350A>G in exon 17, T202T, may be the best proxy for theACEAlu I/D whereas rs4363 and rs4362 may be slightly stronger predictors ofACElevels. Considering reported difficulties in genotypingACEI/D and stronger associations of rs4343 thanACEI/D with plasmaACElevels in Africans, and suitability of rs4343 for allelic mRNA (cDNA) studies, we developed and validated a liquid phase assay for rs4343, which has advantage on both functional and technical grounds. We confirmed that rs4343, is in near perfect linkage disequilibrium (D’=1, r2=0.88, n=64) withACEI/D in Europeans (A and G alleles of rs4343 marking insertion and deletion alleles ofACEI/D respectively).We then studied its association with metabolic and cardiovascular traits in 3253 British women (60–79 years old).Apart from a nominal trend of association with diastolic blood pressure (p anova=0.08; p trend=0.05), no other associations were observed. A post-hoc vascular and general phenome scan revealed no further associations.We conclude thatACEI/D is not a major determinant of metabolic and cardiovascular traits in this population. Liquid phase genotyping of SNP rs4343 may be preferable to gel basedACEI/D genotyping both for technical and functional reasons.

scholarly journals Homozygosity by descent mapping of blood pressure in the Old Order Amish: evidence for sex specific genetic architecture

BMC Genetics ◽  
2007 ◽  
Vol 8 (1) ◽  
Author(s):  
Patrick F McArdle ◽  
Harvey Dytch ◽  
Jeffery R O'Connell ◽  
Alan R Shuldiner ◽  
Braxton D Mitchell ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Architecture ◽  
Old Order Amish ◽  
Old Order

scholarly journals The Genetic Dissection of Ace2 Expression Variation in the Heart of Murine Genetic Reference Population

2020 ◽  
Vol 7 ◽  
Author(s):  
Fuyi Xu ◽  
Jun Gao ◽  
Undral Munkhsaikhan ◽  
Ning Li ◽  
Qingqing Gu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Reference Population ◽  
Functional Enrichment ◽  
P Wave ◽  
Eqtl Mapping ◽  
Cardiac Damage ◽  
Wide Range ◽  
Cardiovascular Traits

Background: A high inflammatory and cytokine burden that induces vascular inflammation, myocarditis, cardiac arrhythmias, and myocardial injury is associated with a lethal outcome in COVID-19. The SARS-CoV-2 virus utilizes the ACE2 receptor for cell entry in a similar way to SARS-CoV. This study investigates the regulation, gene network, and associated pathways of ACE2 that may be involved in inflammatory and cardiovascular complications of COVID-19.Methods: Cardiovascular traits were determined in the one of the largest mouse genetic reference populations: BXD recombinant inbred strains using blood pressure, electrocardiography, and echocardiography measurements. Expression quantitative trait locus (eQTL) mapping, genetic correlation, and functional enrichment analysis were used to identify Ace2 regulation, gene pathway, and co-expression networks.Results: A wide range of variation was found in expression of Ace2 among the BXD strains. Levels of Ace2 expression are negatively correlated with cardiovascular traits, including systolic and diastolic blood pressure and P wave duration and amplitude. Ace2 co-expressed genes are significantly involved in cardiac- and inflammatory-related pathways. The eQTL mapping revealed that Cyld is a candidate upstream regulator for Ace2. Moreover, the protein–protein interaction (PPI) network analysis inferred several potential key regulators (Cul3, Atf2, Vcp, Jun, Ppp1cc, Npm1, Mapk8, Set, Dlg1, Mapk14, and Hspa1b) for Ace2 co-expressed genes in the heart.Conclusions:Ace2 is associated with blood pressure, atrial morphology, and sinoatrial conduction in BXD mice. Ace2 co-varies with Atf2, Cyld, Jun, Mapk8, and Mapk14 and is enriched in the RAS, TGFβ, TNFα, and p38α signaling pathways, involved in inflammation and cardiac damage. We suggest that all these novel Ace2-associated genes and pathways may be targeted for preventive, diagnostic, and therapeutic purposes in cardiovascular damage in patients with systemic inflammation, including COVID-19 patients.

Shared Genetic Architecture Between Sleep and Blood Pressure Traits in Humans

2019 ◽  
Author(s):  
B.E. Cade ◽  
J. Lee ◽  
S.A. Gharib ◽  
D.J. Gottlieb ◽  
K.Y. He ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Genetic Architecture ◽  
Shared Genetic

scholarly journals Association of Genetic Variants With Body-Mass Index and Blood Pressure in Adolescents: A Replication Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Danick Goulet ◽  
Jennifer O’Loughlin ◽  
Marie-Pierre Sylvestre
Keyword(s):  
Blood Pressure ◽  
Body Mass Index ◽  
Systolic Blood Pressure ◽  
Body Mass ◽  
Genetic Variants ◽  
Mixed Models ◽  
Genetic Architecture ◽  
Initial Study ◽  
Positive Results ◽  
Shared Genetic

The strong correlation between adiposity and blood pressure (BP) might be explained in part by shared genetic risk factors. A recent study identified three nucleotide variants [rs16933812 (PAX5), rs7638110 (MRPS22), and rs9930333 (FTO)] associated with both body mass index (BMI) and systolic blood pressure (SBP) in adolescents age 12–18years. We attempted to replicate these findings in a sample of adolescents of similar age. A total of 713 adolescents were genotyped and had anthropometric indicators and blood pressure measured at age 13, 15, 17, and 24years. Using linear mixed models, we assessed associations of these variants with BMI and SBP. In our data, rs9930333 (FTO) was associated with body mass index, but not systolic blood pressure. Neither rs16933812 (PAX5) nor rs7638110 (MRPS22) were associated with body mass index or systolic blood pressure. Although, differences in phenotypic definitions and in genetic architecture across populations may explain some of the discrepancy across studies, nucleotide variant selection in the initial study may have led to false-positive results that could not be replicated.

scholarly journals The genetic architecture of blood pressure

2019 ◽  
Vol 15 (4) ◽  
pp. 192-192
Author(s):  
Ellen F. Carney
Keyword(s):  
Blood Pressure ◽  
Genetic Architecture
Sign in / Sign up

Export Citation Format

Share Document