scholarly journals 279GWAS of heart rate in 87,759 Chinese subjects highlighted its genetic correlations with cardiometabolic traits

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Songchun Yang ◽  
Canqing Yu ◽  
Yu Guo ◽  
Zheng Bian ◽  
Robin G. Walters ◽  
...  

Abstract Background Resting heart rate (RHR) has been associated with risks of mortality and multiple chronic diseases. Previous studies, predominantly conducted in Europeans, have reported 91 independent variants associated with RHR and its genetic correlations with several cardiometabolic traits. Studies from East Asians are lacking. Methods We performed a GWAS for RHR in 87,701 participants aged 30-79 years from China Kadoorie Biobank (CKB). A linear mixed model was used under an additive model. Replication was conducted in 37,251 Chinese participants from CKB and UK Biobank. We conducted LD score regression to quantify genetic correlations across RHR and 11 cardiometabolic traits. Results Only 50 previously reported variants were replicated in CKB (=0.025). We identified ten novel loci associated with RHR (P<5 × 10-8), of which 50 candidate genes were prioritized. RHR showed significant genetic correlations with diastolic blood pressure (rg=0.258, P=5.71 × 10−10), mean arterial pressure (rg=0.225, P=3.08 × 10−8), systolic blood pressure (rg=0.170, P=4.92 × 10−5), plasma glucose (rg=0.197, P=0.003), total cholesterol (rg=0.287, P=0.012), and high-density lipoprotein (rg=0.246, P=0.030). Conclusions We identified ten novel loci associated with RHR in a large Asian cohort. The identified genetic correlations of RHR with blood pressure, glucose, and lipids indicate previously reported association of RHR with risk of all-cause death might be mediated via its correlations with cardiometabolic traits. Key messages

Hypertension ◽  
2021 ◽  
Vol 77 (3) ◽  
pp. 823-832
Author(s):  
Neelakshi Hudda ◽  
Misha Eliasziw ◽  
Scott O. Hersey ◽  
Ellin Reisner ◽  
Robert D. Brook ◽  
...  

Exposure to traffic-related air pollution (TRAP) may contribute to increased prevalence of hypertension and elevated blood pressure (BP) for residents of near-highway neighborhoods. Relatively few studies have investigated the effects of reducing TRAP exposure on short-term changes in BP. We assessed whether reducing indoor TRAP concentrations by using stand-alone high-efficiency particulate arrestance (HEPA) filters and limiting infiltration through doors and windows effectively prevented acute (ie, over a span of hours) increases in BP. Using a 3-period crossover design, 77 participants were randomized to attend three 2-hour-long exposure sessions separated by 1-week washout periods. Each participant was exposed to high, medium, and low TRAP concentrations in a room near an interstate highway. Particle number concentrations, black carbon concentrations, and temperature were monitored continuously. Systolic BP (SBP), diastolic BP, and heart rate were measured every 10 minutes. Outcomes were analyzed with a linear mixed model. The primary outcome was the change in SBP from 20 minutes from the start of exposure. SBP increased with exposure duration, and the amount of increase was related to the magnitude of exposure. The mean change in SBP was 0.6 mm Hg for low exposure (mean particle number and black carbon concentrations, 2500 particles/cm 3 and 149 ng/m 3 ), 1.3 mm Hg for medium exposure (mean particle number and black carbon concentrations, 11 000 particles/cm 3 and 409 ng/m 3 ), and 2.8 mm Hg for high exposure (mean particle number and black carbon concentrations, 30 000 particles/cm 3 and 826 ng/m 3 ; linear trend P =0.019). There were no statistically significant differences in the secondary outcomes, diastolic BP, or heart rate. In conclusion, reducing indoor concentrations of TRAP was effective in preventing acute increases in SBP.


Author(s):  
Tao Huang ◽  
Wenxiu Wang ◽  
Jingjia Wang ◽  
Jun Lv ◽  
Canqing Yu ◽  
...  

Abstract Objectives To examine the direction, strength and causality of the associations of resting heart rate (RHR) with cardiometabolic traits. Methods We assessed the strength of associations between measured RHR and cardiometabolic traits in 506,211 and 372,452 participants from China Kadoorie Biobank (CKB) and UK Biobank (UKB). Mendelian randomization (MR) analyses were used to make causal inferences in 99,228 and 371,508 participants from CKB and UKB, respectively. Results We identified significant, directionally-concordant observational associations between RHR and higher total cholesterol, triglycerides (TG), low-density lipoprotein, C-reactive protein (CRP), glucose, body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) after the Bonferroni correction. MR analyses showed that 10 beat/min higher genetically-predicted RHR were trans-ethnically associated with a higher DBP (beta 2.059 [95%CI 1.544, 2.574] mmHg in CKB; 2.037 [1.845, 2.229] mmHg in UKB), higher CRP (0.180 [0.057, 0.303] log mg/L in CKB; 0.154 [0.134, 0.174] log mg/L in UKB), higher TG (0.052 [-0.009, 0.113] log mmol/L in CKB; 0.020 [0.010, 0.030] log mmol/L in UKB) and higher WHR (0.218 [-0.033, 0.469] % in CKB; 0.225 [0.111, 0.339] % in UKB). In the opposite direction, higher genetically-predicted SBP, TG, glucose, WHR and lower high-density lipoprotein were associated with elevated RHR. Conclusion Our large-scale analyses provide causal evidence between RHR and cardiometabolic traits, highlighting the importance of monitoring heat rate as a means of alleviating the adverse effect of metabolic disorders.


Author(s):  
Alice Iannaccone ◽  
Daniele Conte ◽  
Cristina Cortis ◽  
Andrea Fusco

Internal load can be objectively measured by heart rate-based models, such as Edwards’ summated heart rate zones, or subjectively by session rating of perceived exertion. The relationship between internal loads assessed via heart rate-based models and session rating of perceived exertion is usually studied through simple correlations, although the Linear Mixed Model could represent a more appropriate statistical procedure to deal with intrasubject variability. This study aimed to compare conventional correlations and the Linear Mixed Model to assess the relationships between objective and subjective measures of internal load in team sports. Thirteen male youth beach handball players (15.9 ± 0.3 years) were monitored (14 training sessions; 7 official matches). Correlation coefficients were used to correlate the objective and subjective internal load. The Linear Mixed Model was used to model the relationship between objective and subjective measures of internal load data by considering each player individual response as random effect. Random intercepts were used and then random slopes were added. The likelihood-ratio test was used to compare statistical models. The correlation coefficient for the overall relationship between the objective and subjective internal data was very large (r = 0.74; ρ = 0.78). The Linear Mixed Model using both random slopes and random intercepts better explained (p < 0.001) the relationship between internal load measures. Researchers are encouraged to apply the Linear Mixed Models rather than correlation to analyze internal load relationships in team sports since it allows for the consideration of the individuality of players.


2021 ◽  
Vol 8 (7) ◽  
pp. 129
Author(s):  
Jennifer Davis ◽  
Anthea L. Raisis ◽  
Claire R. Sharp ◽  
Rachel E. Cianciolo ◽  
Steven C. Wallis ◽  
...  

Resveratrol has been shown to preserve organ function and improve survival in hemorrhagic shock rat models. This study investigated whether seven days of oral resveratrol could improve hemodynamic response to hemorrhage and confer benefits on risk of acute kidney injury (AKI) without inducing coagulopathy in a canine model. Twelve greyhound dogs were randomly allocated to receive oral resveratrol (1000 mg/day) or placebo for seven days prior to inducing hemorrhage until a targeted mean blood pressure of ≤40 mmHg was achieved. AKI biomarkers and coagulation parameters were measured before, immediately following, and two hours after hemorrhage. Dogs were euthanized, and renal tissues were examined at the end of the experiment. All investigators were blinded to the treatment allocation. A linear mixed model was used to assess effect of resveratrol on AKI biomarkers and coagulation parameters while adjusting for volume of blood loss. A significant larger volume of blood loss was required to achieve the hypotension target in the resveratrol group compared to placebo group (median 64 vs. 55 mL/kg respectively, p = 0.041). Although histological evidence of AKI was evident in all dogs, the renal tubular injury scores were not significantly different between the two groups, neither were the AKI biomarkers. Baseline (pre-hemorrhage) maximum clot firmness on the Rotational Thromboelastometry (ROTEM®) was stronger in the resveratrol group than the placebo group (median 54 vs. 43 mm respectively, p = 0.009). In summary, seven days of oral resveratrol did not appear to induce increased bleeding risk and could improve greyhound dogs’ blood pressure tolerance to severe hemorrhage. Renal protective effect of resveratrol was, however, not observed.


2021 ◽  
Author(s):  
Rada R Veeneman ◽  
Jentien M Vermeulen ◽  
Abdel Abdellaoui ◽  
Eleanor Sanderson ◽  
Robyn E Wootton ◽  
...  

Importance: Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to fully unravel the nature of this relationship. Objective: Investigate genetic correlations and potential bi-directional effects between liability to schizophrenia and CVD. Design, setting, and participants: We obtained summary-data of genome-wide-association studies of schizophrenia (N=130,644), heart failure (N=977,323), coronary artery disease (N=332,477), systolic and diastolic blood pressure (N=757,601), heart rate variability (N=46,952), QT interval (N=103,331), early repolarization and dilated cardiomyopathy ECG patterns (N=63,700). We computed genetic correlations with linkage disequilibrium score regression and conducted bi-directional Mendelian randomization (MR). With multivariable MR, we investigated whether associations were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. To ensure robustness, we applied a range of sensitivity methods. Main outcomes and measures: Schizophrenia, heart failure, coronary artery disease, systolic blood pressure, diastolic blood pressure, heart rate variability, QT interval, early repolarization, dilated cardiomyopathy. Results: Genetic correlations between liability to schizophrenia and CVD were close to zero (-0.02 to 0.04). With MR, we found robust evidence that liability to schizophrenia increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization risk, largely mediated by BMI and lipid levels. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting previous studies. In the other direction, there was weak evidence that higher systolic, but not diastolic, blood pressure increases schizophrenia risk. Conclusions and relevance: Our findings indicate that liability to schizophrenia increases the risk of heart failure, and that this is not mediated by key health behaviours. This is consistent with the notion that schizophrenia is characterised by a systemic dysregulation of the body (including inflammation and oxidative stress) with detrimental effects on the heart. To decrease cardiovascular mortality among schizophrenia patients, priority should lie with optimal treatment and interventions in early stages of psychoses. We also identified early repolarization, currently understudied, as a potential CVD marker among patients with schizophrenia.


1985 ◽  
Vol 30 (2) ◽  
pp. 106-110 ◽  
Author(s):  
D. J. Webb ◽  
M. J. Hutcheson ◽  
M. P. Robertson ◽  
G. D. Murray ◽  
A. R. Lorimer ◽  
...  

In a 12-week double-blind randomised study the efficacy of atenolol and a new longer-acting formulation of trimazosin were compared when given once daily in patients with mild to moderate hypertension. Two parallel groups, each consisting of 18 patients, were studied. At randomisation the two groups were well matched for age and sex distribution. They were also well matched for blood pressure, pulse rate and body weight; these latter measurements were recorded at regular intervals during the 12 weeks of study. Atenolol produced substantial reduction in both systolic and diastolic blood pressure, and in heart rate, during 12 weeks of treatment. This therapeutic effect was maintained until the next dose after 24 hours. Trimazosin, by comparison, failed to reduce either systolic or diastolic pressure, or to alter heart rate. Side effects were minor with both agents and compliance with treatment was good. Atenolol caused significant elevation of plasma concentration of triglyceride, with reduction in high density lipoprotein concentration when compared with trimazosin. In conclusion, atenolol was confirmed as an effective agent for the treatment of mild to moderate hypertension. By comparison trimazosin in the longer-acting formulation was ineffective in this study. However, trimazosin may still find a place in treatment if used at higher dose.


2017 ◽  
Vol 9 (8) ◽  
pp. 63
Author(s):  
Jairo Azevedo Junior ◽  
Juliana Petrini ◽  
Gerson Barreto Mourão ◽  
José Bento Sterman Ferraz

Variance components and genetic parameters of economically relevant traits in livestock, whether continuous or categorical, can be estimated by methods computationally available providing support for the selection and mating of animals in breeding programs. The objectives of this paper were to obtain and compare the variance components estimates for visual traits under continuous or categorical distribution in single-trait analysis and their correlations with continuous productive traits in two-trait analysis. Data of conformation (CONF), precocity of fat deposition (PREC) and muscling (MUSC) visual scores evaluated at 18 months of age as well as the weight at 18 months of age (YW) were collected from animals born from 2000 to 2012, in Nellore cattle herds raised in Southeastern and Central Western tropical regions of Brazil. Methods III of Henderson, Restricted Maximum Likelihood (REML), Bayesian Inference and generalized linear mixed model (GLMM) were tested. Variance components obtained from single-trait analysis were similar to those obtained from two-trait analysis. The estimates of heritability (h2) for the visual scores ranged from 0.1081 to 0.2190. Heritability estimates for traits evaluated by visual scores have moderate to high magnitude justifying the inclusion of visual scores as selection criteria in animal breeding and the selection of animals with higher scores for mating. High genetic correlations between yearling weight and morphological traits were verified. For visual scores of conformation, precocity and muscling, the most suitable model based on one-trait or two-trait analyses considered an animal model, a linear distribution of the data and the estimation method of the components of (co)variance based on Bayesian methodology.


1968 ◽  
Vol 10 (4) ◽  
pp. 853-864 ◽  
Author(s):  
Gunther Schlager

Analysis of data from crosses between the A/J and SWR/J strains showed that the genic action of the alleles affecting blood pressure by which these strains differ act additively in the males. The apparent partial dominance observed in the female data was due to the truncation of the upper tail of the distribution of blood pressures in the SWR/J strain. When the data were corrected for this truncation, an additive model of inheritance also fitted the female data.The genetic control of hematocrit per cent and relative kidney weight was indicated. The inheritance is additive for hematocrit, and is more complex for relative kidney weight where epistatic interactions are involved. The A/J and SWR/J strains did not differ in renin granularity.The interrelationship of hematocrit per cent, relative kidney weight, renin granularity, and blood pressure was investigated. Hematocrit and renin granularity were considered not to be the source of the blood pressure differences between the two strains. Significant phenotypic and genetic correlations between relative kidney weight and blood pressure were discernible in the male data, but not among the females.


2020 ◽  
Vol 39 (01) ◽  
Author(s):  
Kefale Getahun ◽  
Million Tadesse ◽  
Direba Hundie

This study was aimed to generate information on variance components and the resulting genetic parameters (heritability, repeatability, genetic and phenotypic correlations and genetic trends) of some economic traits of Borena and its crosses with Holstein Friesian dairy cattle maintained at Holetta agricultural research center dairy farm. Traits studied were age at first service (AFS), age at first calving (AFC), calving interval (CI), days open (DO) and number of service per conception (NSC). Overall, 11331 dairy cattle reproductive performance records were used for the study. WOMBAT, which is a software package for quantitative genetic analysis of continuous traits, fitting a linear, mixed model; estimates of covariance components and the resulting genetic parameters were employed and obtained. Heritability values of reproductive traits were from very low (0.071, 0.082 and 0.012) for CI, DO and NSC to moderate (0.3 and 0.22) for AFC and AFS traits. Repeatability estimate for CI, DO and NSC were low (0.17, 0.17 and 0.129). Strong and positive genetic correlation (0.98) was appeared between AFS and AFC traits. Negative genetic correlations were observed between AFS and DO (-0.001), AFC and DO (-0.05), AFS and NSC (-0.022), AFC and NSC (-0.29) and CI and NSC (-0.31). AFS were negative phenotypic correlation with CI, DO and NSC. Similarly, AFC was negative phenotypic correlation with CI and DO. Low phenotypic correlation was observed between AFC and NSC, CI and DO, CI and NSC and, DO and NSC. Strong and positive phenotypic correlation was appeared between AFS and AFC. The regression coefficient of mean breeding value for NSC, CI, DO, AFC and AFS on year of birth were -0.0066x+13.25 times/year, -1.19x+2387.4 days/year, -1.23x+2445.6 days/year, 0.2x-410 months/year and 0.48x-980 months/year, respectively.


Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1256-1262
Author(s):  
Balewgizie S. Tegegne ◽  
Tengfei Man ◽  
Arie M. van Roon ◽  
Nigus G. Asefa ◽  
Harriëtte Riese ◽  
...  

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all P <0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (−0.20/−0.16) and with diastolic BP (−0.15/−0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, −0.08 to −0.23) and diastolic BP (range, −0.20 to −0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap.


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