Showing papers by "Christopher J. O'Donnell published in 2018"

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future

Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

Abstract: The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 100 years of follow-up Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000) Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease) Analysis of genetic data and blood lipid measurements from over 300,000 participants in the Million Veteran Program identifies new associations for blood lipid traits

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Association of interleukin 6 receptor variant with cardiovascular disease effects of interleukin 6 receptor blocking therapy: A phenome - Wide association study

Abstract: Importance Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene–drug pair provides an example to test whether associations ofIL6RSNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade. Objective To determine whether screening for clinical associations with theIL6RSNP in a phenome-wide association study (PheWAS) using EHR biobank data can identify drug effects from IL6R clinical trials. Design, Setting, and Participants Diagnosis codes and routine laboratory measurements were extracted from the VA Million Veteran Program (MVP); diagnosis codes were mapped to phenotype groups using published PheWAS methods. A PheWAS was performed by fitting logistic regression models for testing associations of theIL6RSNPs with 1342 phenotype groups and by fitting linear regression models for testing associations of theIL6RSNP with 26 routine laboratory measurements. Significance was reported using a false discovery rate of 0.05 or less. Findings were replicated in 2 independent cohorts using UK Biobank and Vanderbilt University Biobank data. The Million Veteran Program included 332 799 US veterans; the UK Biobank, 408 455 individuals from the general population of the United Kingdom; and the Vanderbilt University Biobank, 13 835 patients from a tertiary care center. Exposures IL6RSNPs (rs2228145;rs4129267). Main Outcomes and Measures Phenotypes defined byInternational Classification of Diseases, Ninth Revisioncodes. Results Of the 332 799 veterans included in the main cohort, 305 228 (91.7%) were men, and the mean (SD) age was 66.1 (13.6) years. TheIL6RSNP was most strongly associated with a reduced risk of aortic aneurysm phenotypes (odds ratio, 0.87-0.90; 95% CI, 0.84-0.93) in the MVP. We observed known off-target effects of IL6R blockade from clinical trials (eg, higher hemoglobin level). The reduced risk for aortic aneurysms among those with theIL6RSNP in the MVP was replicated in the Vanderbilt University Biobank, and the reduced risk for coronary heart disease was replicated in the UK Biobank. Conclusions and Relevance In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of theIL6RSNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.

A comprehensive evaluation of the genetic architecture of sudden cardiac arrest.

Abstract: Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

ADP Platelet Hyperreactivity Predicts Cardiovascular Disease in the FHS (Framingham Heart Study).

Abstract: Background Platelet function is associated with adverse events in patients with cardiovascular disease (CVD). Methods and Results We examined associations of baseline platelet function with incident CVD events in the community‐based FHS (Framingham Heart Study). Participants free of prevalent CVD and without recent aspirin treatment with available data in the Framingham Offspring cohort (1991–1995) and Omni cohort (1994–1998) were included. Platelet function was measured with light transmission aggregometry using collagen (1.9 μg/mL), ADP (0.05–15 μmol/L), and epinephrine (0.01–15 μmol/L). We used proportional hazards models to analyze incident outcomes (myocardial infarction/stroke, CVD, and CVD mortality) with respect to platelet measures. The study sample included 2831 participants (average age, 54.3 years; 57% women). During follow‐up (median, 20.4 years), we observed 191 composite incident myocardial infarction or stroke events, 432 incident CVD cases, and 117 CVD deaths. Hyperreactivity to ADP and platelet aggregation at ADP concentration of 1.0 μmol/L were significantly associated with incident myocardial infarction/stroke in a multivariable model (hazard ratio, 1.68 [95% confidence interval, 1.13–2.50] [ P =0.011] for hyperreactivity across ADP doses; and hazard ratio, 1.16 [95% confidence interval, 1.02–1.33] [ P =0.029] for highest quartile of ADP response at 1.0 μmol/L versus others). No association was observed for collagen lag time or any epinephrine measures with incident myocardial infarction or stroke. Conclusions Intrinsic hyperreactivity to low‐dose ADP in our community‐based sample, who were free of CVD and any antiplatelet therapy, is associated with future arterial thrombosis during a 20‐year follow‐up. These findings reinforce ADP activation inhibition as a critical treatment paradigm and encourage further study of ADP inhibitor‐refractive populations.

Astronaut Cardiovascular Health and Risk Modification (Astro-CHARM) Coronary Calcium Atherosclerotic Cardiovascular Disease Risk Calculator

Abstract: Background: Coronary artery calcium (CAC) is a powerful novel risk indicator for atherosclerotic cardiovascular disease (ASCVD). Currently, there is no available ASCVD risk prediction tool that int...

A new look at the decomposition of agricultural productivity growth incorporating weather effects.

Abstract: Random fluctuations in temperature and precipitation have substantial impacts on agricultural output. However, the contribution of these changing configurations in weather to total factor productivity (TFP) growth has not been addressed explicitly in econometric analyses. Thus, the key objective of this study is to quantify and to investigate the role of changing weather patterns in explaining yearly fluctuations in TFP. For this purpose, we define TFP to be a measure of total output divided by a measure of total input. We estimate a stochastic production frontier model using U.S. state-level agricultural data incorporating growing season temperature and precipitation, and intra-annual standard deviations of temperature and precipitation for the period 1960-2004. We use the estimated parameters of the model to compute a TFP index that has good axiomatic properties. We then decompose TFP growth in each state into weather effects, technological progress, technical efficiency, and scale-mix efficiency changes. This approach improves our understanding of the role of different components of TFP in agricultural productivity growth. We find that annual TFP growth averaged 1.56% between 1960 and 2004. Moreover, we observe substantial heterogeneity in weather effects across states and over time.

Productivity and Efficiency Analysis: An Economic Approach to Measuring and Explaining Managerial Performance

Abstract: This book provides a coherent description of the main concepts and statistical methods used to analyse economic performance. The focus is on measures of performance that are of practical relevance to policy makers. Most, if not all, of these measures can be viewed as measures of productivity and/or efficiency. Linking fields as diverse as index number theory, data envelopment analysis and stochastic frontier analysis, the book explains how to compute measures of input and output quantity change that are consistent with measurement theory. It then discusses ways in which meaningful measures of productivity change can be decomposed into measures of technical progress, environmental change, and different types of efficiency change. The book is aimed at graduate students, researchers, statisticians, accountants and economists working in universities, regulatory authorities, government departments and private firms. The book contains many numerical examples. Computer codes and datasets are available on a companion website.

Maintenance of Ideal Cardiovascular Health and Coronary Artery Calcium Progression in Low-Risk Men and Women in the Framingham Heart Study.

Abstract: Background— Ideal cardiovascular health (CVH) is associated with a lower risk of cardiovascular disease and freedom from coronary artery calcium (CAC). Prospective data on the association between maintenance of optimal CVH and the progression of subclinical coronary atherosclerosis are limited. We assessed the influence of unfavorable versus favorable CVH on the incidence of CAC progression. Methods and Results— The study population consisted of 1119 FHS (Framingham Heart Study) participants who attended the serial FHS MDCT I and MDCT II study (Multi-Detector Computed Tomography) and had a zero Agatston CAC score at baseline. CVH status was defined using 6 CVH metrics from the American Heart Association definition. CAC progression was defined by an increase in Agatston CAC score to ≥3.4. Generalized estimating equations were applied to identify significant associations of CAC progression with both the baseline measurement of CVH and the longitudinal maintenance of CVH. After follow-up (mean, 6.1 years), we observed CAC progression in 191 participants (17.1%). Participants with unfavorable CVH at baseline had a greater risk of CAC progression (odds ratio, 2.43; 95% confidence interval, 1.40–4.23; P =0.0017). In addition, each unit decrease in ideal CVH metric was associated with an increase in CAC progression (odds ratio, 1.15; 95% confidence interval, 0.99–1.34; P =0.067), after adjustment for baseline ideal CVH metrics. Conclusions— Significant associations between an unfavorable CVH profile and CAC progression support public health measures that seek to prevent cardiovascular disease by promoting favorable CVH profiles in persons free of clinical and subclinical cardiovascular disease.

Australian university productivity growth and public funding revisited

Abstract: The Australian Government provides basic operating grants to universities, which are used to teach domestic undergraduate students. It imposes a productivity offset on the grants to encourage improvements in university productivity. But it is not transparent and does not vary across universities. Thus, universities have little incentive to improve performance. This paper develops an alternative framework that uses incentive regulation to allocate these grants to universities, which provides stronger incentives for universities to improve productivity. Regulators often use a similar framework to set prices for natural monopoly services such as utilities and public transport. Under incentive regulation, the basic operating grants could be reduced, on average, by 1.76% per annum over 5 years, which is about $100 million per annum. This finding is contrary to several recent Australian Government inquires that suggest the basic operating grant is inadequate and that this compromises the quality of unde...

Common Coding Variants in SCN10A Are Associated With the Nav1.8 Late Current and Cardiac Conduction.

Abstract: Background: Genetic variants at the SCN5A / SCN10A locus are strongly associated with electrocardiographic PR and QRS intervals. While SCN5A is the canonical cardiac sodium channel gene, the role of SCN10A in cardiac conduction is less well characterized. Methods: We sequenced the SCN10A locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology. Results: We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium ( r 2 =0.86) with each other to be the strongest signals for PR (rs10428132, β=−4.74, P =1.52×10 −14 ) and QRS intervals (rs6599251, QRS β=−0.73; P =1.2×10 −4 ), respectively. Although these variants were not associated with SCN5A or SCN10A expression in human atrial tissue (n=490), they were in high linkage disequilibrium ( r 2 ≥0.72) with a common SCN10A missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%, P =0.03, and I962V+V1073A, 22.4±0.8%, P =0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%, P =0.03). Conclusions: Our findings suggest an association between genetic variation in SCN10A , the late sodium current, and alterations in cardiac conduction.

Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

Abstract: In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.

A phenotyping algorithm to identify acute ischemic stroke accurately from a national biobank: the Million Veteran Program

Abstract: Background Large databases provide an efficient way to analyze patient data. A challenge with these databases is the inconsistency of ICD codes and a potential for inaccurate ascertainment of cases. The purpose of this study was to develop and validate a reliable protocol to identify cases of acute ischemic stroke (AIS) from a large national database. Methods Using the national Veterans Affairs electronic health-record system, Center for Medicare and Medicaid Services, and National Death Index data, we developed an algorithm to identify cases of AIS. Using a combination of inpatient and outpatient ICD9 codes, we selected cases of AIS and controls from 1992 to 2014. Diagnoses determined after medical-chart review were considered the gold standard. We used a machine-learning algorithm and a neural network approach to identify AIS from ICD9 codes and electronic health-record information and compared it with a previous rule-based stroke-classification algorithm. Results We reviewed administrative hospital data, ICD9 codes, and medical records of 268 patients in detail. Compared with the gold standard, this AIS algorithm had a sensitivity of 91%, specificity of 95%, and positive predictive value of 88%. A total of 80,508 highly likely cases of AIS were identified using the algorithm in the Veterans Affairs national cardiovascular disease-risk cohort (n=2,114,458). Conclusion Our algorithm had high specificity for identifying AIS in a nationwide electronic health-record system. This approach may be utilized in other electronic health databases to accurately identify patients with AIS.

The artefacts of death: CT post-mortem findings.

Abstract: Post-mortem CT is an increasingly used tool for investigating cause of death. While sharing many similarities with pre-mortem imaging, a number of unique artefacts occur at post-mortem CT, and these have the potential to mask underlying disease processes. It is vital that the artefacts associated with the process of dying and decompositional changes are recognised to avoid misdiagnosis. The following pictorial review discusses and illustrates the important and common post-mortem changes.

Baseline Characterization and Annual Trends of Body Mass Index for a Mega-Biobank Cohort of US Veterans 2011-2017.

Abstract: Aim: Million Veteran Program (MVP) is the largest ongoing mega-cohort biobank program in the US with 570,131 enrollees as of May 2017. The primary aim is to describe demographics, military service, and major diseases and comorbidities of the MVP cohort. Our secondary aim is to examine body mass index (BMI), a proxy for general health, among enrollees. Materials and Method: The study population consists of Veterans who actively use the Veterans Health Administration in the US. Data evaluated in this paper combine health information from multiple sources to provide the most comprehensive demographic profile and information on height and weight of MVP enrollees. A standardized cleaning algorithm was used to curate the demographic variables for each participant in MVP. For height and weight, we derived a final data point for each participant to evaluate BMI. Statistical Analysis Used: Multivariable logistic regression was used to compare the differences in BMI categories across enrollment years adjusting for gender, race, and age. P < 0.05 was considered statistically significant. All analyses were conducted using Statistical Analysis System 9.2. Results: The MVP cohort consists of 90.4% of males with an average age of 61.9 years (standard deviation [SD] = 13.9). MVP is the largest multiethnic biobank cohort within the Veteran population with 73.9% White, 19.0% Black, and 6.5% Hispanic. The most common self-reported disease was hypertension (62.6%) for males and depression (47.5%) for females. Mean BMI was 29.7 kg/m2 (SD = 5.8) with 38.2% obese and 42.3% overweight. Conclusions: Our findings suggest that demographic representation in MVP is similar to the Veterans Health Administration population and contrasts with the overall National Health and Nutrition Examination Survey US population. The prevalence of overweight and obese is high among US Veterans, and future studies will examine the role of BMI and disease risk in the Veteran population.

Prevalence of Ideal Cardiovascular Health Metrics in the Million Veteran Program

Abstract: No data exist on the prevalence of ideal cardiovascular health metrics in a national sample of U.S. veterans. We assessed the prevalence of ideal Life's Simple Seven (LSS) metrics in a cross-sectional study of 554,855 U.S. veterans enrolled in the Million Veteran Program (MVP) from 2011 to 2017. We used the American Heart Association's established criteria to categorize each LSS metric as either poor, intermediate, or ideal for a veteran at time of MVP enrollment. Information on adiposity/body mass index, smoking status, diet, and physical activity was obtained from self-reported survey data, and clinical measurements for total cholesterol, blood pressure, and plasma glucose were obtained from electronic health records. Complete data on all LSS health factors were available for 201,745 veterans. The prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal cardiovascular health metrics was 29.2%, 34.6%, 22.6%, 10.0%, 3.0%, 0.6%, <0.1%, and 0%, respectively. The frequency of ideal body mass index, physical activity, smoking status, total cholesterol, blood pressure, and plasma glucose was 19.4%, 3.8%, 27.0%, 21.8%, 17.8%, and 34.5%, respectively, in our study population. Among the 7 metrics, MVP participants were least likely to achieve ideal diet (0.4%), particularly the recommendation for fruit and vegetable (at least 4.5 cups/day) intake. Our data show an extremely low prevalence of ideal cardiovascular health factors among veterans in the MVP, especially for diet and physical activity. These findings underscore the need to improve adherence to modifiable lifestyle factors that could result in subsequent reduction in cardiovascular disease burden among veterans.

Longitudinal Associations of Pericardial and Intrathoracic Fat With Progression of Coronary Artery Calcium (from the Framingham Heart Study).

Abstract: Cross-sectional studies have shown that pericardial fat is associated with atherosclerotic burden above and beyond generalized and central adiposity. Whether pericardial fat is longitudinally associated with coronary artery calcium (CAC) has not been firmly established. We examined the associations between cardiac ectopic fat including pericardial and intrathoracic fat with CAC progression and incidence in a community-based study setting. Study participants were from the Framingham Heart Study Offspring and Third Generation Cohorts who underwent multidetector computed tomography at 2 consecutive examinations (2002 to 2005 and 2008 to 2011) for the assessment of CAC. Multivariable-adjusted regression models were used to evaluate the associations between cardiac ectopic fat with CAC. Nonlinear associations were also examined. We included 1,732 participants (49.6% women, mean age 49.9 years). Of the 1,024 participants with a CAC score = 0 at baseline, 197 individuals developed a CAC score > 0 (19.2%) during 6.1 years of follow-up. The remaining 708 participants with a CAC score > 0 at baseline were eligible for CAC progression analysis. We identified nonlinear association between pericardial fat and CAC progression. Higher pericardial fat was associated with higher CAC progression only for those participants with pericardial fat higher than the median value (β = 56.0, p = 0.04). Intrathoracic fat was linearly associated with CAC progression (β = 23.0, p = 0.02). However, all of these associations did not persist after additional adjustment for body mass index, abdominal visceral adipose tissue, or waist circumference (all p ≥ 0.14). Neither pericardial nor intrathoracic fat were associated with CAC incidence (all p ≥ 0.33). Overall, both of the cardiac ectopic fat measures were longitudinally associated with CAC progression.

Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.

Abstract: Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Effects of Genetic Variants Associated with Familial Hypercholesterolemia on Low-Density Lipoprotein-Cholesterol Levels and Cardiovascular Outcomes in the Million Veteran Program.

Abstract: Background: Familial hypercholesterolemia (FH) is characterized by inherited high levels of LDL-C (low-density lipoprotein cholesterol) and premature coronary heart disease. Over a thousand low-fre...

Lp-PLA2, scavenger receptor class B type i gene (SCARB1) rs10846744 variant, and cardiovascular disease

Abstract: Background We previously reported association of SCARB1 SNP rs10846744 with common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since rs10846744 has been reported in association with Lp-PLA2 mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis. Methods We first examined association of rs10846744 in CVD in multiple large-scale consortium-based genome-wide association studies. We further examined 27 parameters of interest, including Lp-PLA2 mass and activity, inflammatory markers, and plasma phospholipid fatty acids, and fatty acid ratios in participants from the Multi-Ethnic Study of Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744 with cIMT and incident CVD. Finally, we examined the association of rs10846744 with Lp-PLA2 activity, cardiovascular outcomes, and interaction with the Lp-PLA2 inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies. Results SCARB1 rs10846744 was associated with coronary artery disease events in CARDIoGRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P = 1.4x10-4). In combined analysis across race/ethnic groups in MESA, rs10846744 was associated with Lp-PLA2 mass (P = 0.04) and activity (P = 0.001), homocysteine (P = 0.03), LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01), docosapentaenoic acid [DPA] (P = 0.04), DPA/ eicosapentaenoic acid [EPA] ratio (P = 0.002), and DHA/EPA ratio (P = 0.008). Lp-PLA2 activity was identified as a mediator of rs10846744 with cIMT in a basic model (P = 8x10-5), but not after adjustment for CVD risk factors. There was no interaction or modifier effect of the Lp-PLA2 inhibitor darapladib assignment on the relationship between rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. Summary SCARB1 rs10846744 is significantly associated with Lp-PLA2 activity, atherosclerosis, and CVD events, but Lp-PLA2 activity is not a mediator in the association of rs10846744 with cIMT in MESA.

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Alien and native plant seed dispersal by vehicles.

Abstract: Vehicles play a significant role in spreading plants, both in terms of quantity and quality (species). This study was conducted in Southeast Queensland to determine the role of utility vehicles in spreading seeds. These vehicles were found to carry up to 397 seeds per vehicle and in all four seasons of the year, with the majority of these species being alien to Australia and/or Queensland. The largest seed loads were found in autumn in this summer rainfall environment. Seeds were shown to attach to all parts of the vehicle, often in mud picked up from the ground, affixed directly to the engine or radiator, or carried into the cabin by the driver. Therefore, much of the seed load is to be found on the underside, on the back and front mudguards while smaller collections were found in the cabin, on the radiator and engine, and on the tyres. Fewer viable seeds were found on the engine, presumably as desiccation and heat contributed more to their death on this part of the vehicle. One method used to reduce weed seed spread by vehicles in Queensland is washing and vacuuming of vehicles. From the present study, these procedures would need to be applied to all parts of the vehicle and in all seasons of the year.

Effect of isolated left bundle-branch block on biventricular volumes and ejection fraction: a cardiovascular magnetic resonance assessment.

Abstract: Background Left bundle branch block (LBBB) is associated with abnormal left ventricular (LV) contraction, and is frequently associated with co-morbid cardiovascular disease, but the effect of an isolated (i.e. in the absence of cardiovascular dissease) LBBB on biventricular volumes and ejection fraction (EF) is not well characterized. The objective of this study was to compare LV and right ventricular (RV) volumes and EF in adults with an isolated LBBB to matched healthy controls and to population-derived normative values, using cardiovascular magnetic resonance (CMR) imaging.

Large-Scale Genomic Biobanks and Cardiovascular Disease.

Abstract: Cardiovascular disease is a leading cause of morbidity and mortality worldwide and is the focus of extensive biomedical research. Large genetic consortia combining data from many traditional prospective cohort and ascertained case-control study designs have facilitated the discovery of genetic associations for a variety of cardiovascular diseases including diabetes, coronary artery disease, and hypertension. Biobank-based genetic studies offer an alternative whereby large populations are genotyped and linked to electronic health records. Biobank sample sizes worldwide have surpassed even the largest genetic consortia and have yielded key insights into the genetic determinants of both common and rare cardiovascular phenotypes. Herein, we provide an overview of the largest genomic biobanks and discuss the relevant advantages and challenges inherent to the biobank model of cohort generation and genomic study design.