Genetic variation in NOS1AP is associated with sudden cardiac death: evidence from the Rotterdam Study.

Common variation within the nitric oxide-1 synthase activator protein (NOS1AP) locus is strongly related to QT interval, a sudden cardiac death (SCD) risk factor. A recent report describes common variation in NOS1AP associated with SCD in a US population of European ancestry. The objective of the current study was to obtain additional evidence by investigating the association between NOS1AP variants and SCD in the prospective population-based Rotterdam Study.

Sonographic assessment of abdominal fat distribution in infancy.

There is growing evidence that not only the total amount of fat, but also the distribution of body fat determines risks for metabolic and cardiovascular disease. Developmental studies on factors influencing body fat distribution have been hampered by a lack of appropriate techniques for measuring intraabdominal fat in early life. Sonography, which is an established method for assessing abdominal fat distribution in adults, has not yet been evaluated in infants.

Evaluation of risk prediction updates from commercial genome-wide scans.

Purpose: Commercial internet-based companies offer genome-wide scans to predict the risk of common diseases and personalize nutrition and lifestyle recommendations. These risk estimates are updated with every new gene discovery.

Methods: To assess the benefits of updating risk information in commercial genome-wide scans, we compared type 2 diabetes risk predictions based on TCF7L2 alone, 18 polymorphisms alone, and 18 polymorphisms plus age, sex, and body mass index.

Biomarkers of left atrial volume: a longitudinal study in patients with end stage renal disease.

Left atrial volume (LAV) has recently emerged as a useful biomarker for risk stratification and risk monitoring in patients with end stage renal disease. We investigated the relationship between cardiac natriuretic peptides (atrial natriuretic peptide [ANP] and brain natriuretic peptide [BNP]) and norepinephrine (NE) with LAV and LAV changes over time in 199 end stage renal disease patients. At baseline, LAV was directly related to BNP (r=0.

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.

We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

Context: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.

Objective: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples.

Design, Setting, And Participants: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.

NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance.

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.

Cardiac structures track during the first 2 years of life and are associated with fetal growth and hemodynamics: the Generation R Study.

Background: The aim of this study is to examine whether cardiac size and function track in early childhood and are associated with fetal and early postnatal growth and blood flow characteristics.

Methods: This study was embedded in a population-based prospective cohort study from fetal life onward. Fetal growth and fetal and placental blood flow parameters in second and third trimester of pregnancy were measured by ultrasound and Doppler.

Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study.

Objective: We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes.

Design: Population-based birth cohort study.

Setting: Data of pregnant women and their children in Rotterdam, the Netherlands.

Risk factors for coronary, aortic arch and carotid calcification; The Rotterdam Study.

This study was performed to examine the association of cardiovascular risk factors with calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT). This study was embedded in the Rotterdam Study, a population-based study in subjects aged 55 years and over. From October 2003 until December 2004, subjects were invited to undergo a MSCT scan.

Dietary intake of fish and omega-3 fatty acids in relation to long-term dementia risk.

Background: Greater fish and omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake may reduce dementia risk; however, previous studies have reported conflicting results, which were largely based on short-term follow-up.

Objective: The objective was to study the dietary consumption of fish and omega-3 PUFAs in relation to long-term dementia risk.

Design: We studied 5395 participants aged > or =55 y in the Rotterdam Study who were free of dementia and reported dietary information at baseline.

Fetal and postnatal growth and blood pressure at the age of 2 years. The Generation R Study.

Objectives: To examine which fetal and postnatal growth characteristics are associated with blood pressure (BP) in children at the age of 2 years.

Methods: This study was embedded in the Generation R Study, a population-based prospective cohort study from early fetal life onwards. Fetal ultrasound examinations were carried out at the visits in one of the research centers in early, mid- and late pregnancy.

Loci at chromosomes 13, 19 and 20 influence age at natural menopause.

We conducted a genome-wide association study for age at natural menopause in 2,979 European women and identified six SNPs in three loci associated with age at natural menopause: chromosome 19q13.4 (rs1172822; -0.4 year per T allele (39%); P = 6.

Multiple loci associated with indices of renal function and chronic kidney disease.

Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity. We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60 ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases).

Genome-wide association study of blood pressure and hypertension.

Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7).

Genome-wide association meta-analysis for total serum bilirubin levels.

Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism. We aimed to identify genetic contributors to variability in serum bilirubin levels by combining results from three genome-wide association studies (Framingham heart study, n = 3424; Rotterdam study, n = 3847; Age, Gene, Environment and Susceptibility-Reykjavik, n = 2193). Meta-analysis showed strong replication for a genetic influence on serum bilirubin levels of the UGT1A1 locus (P < 5 x 10(-324)) and a 12p12.

Genetic variation in the fibrinogen-alpha and fibrinogen-gamma genes in relation to arterial stiffness: the Rotterdam Study.

Objective: Arterial stiffness increases with age and predicts cardiovascular disease. Fibrinogen is an acute-phase protein and some studies showed an association with arterial stiffness. We studied genetic variation in the fibrinogen-alpha (FGA) and fibrinogen-gamma (FGG) genes, by means of single nucleotide polymorphisms (FGA: -58 G/A, 1374 G/A, 1526 T/C, 312 Thr/Ala, and FGG: 4288 G/A, 6326 G/A, 7792 T/C) and resultant haplotypes in relation to arterial stiffness.

Inverse association between dairy intake and hypertension: the Rotterdam Study.

Background: Little is known about the effect of different types of dairy food products on the development of hypertension.

Objective: The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products.

Design: We examined the relation between dairy intake and incident hypertension in 2245 participants of the Rotterdam Study aged > or =55 y with complete dietary and blood pressure data, who were free of hypertension at baseline (1990-1993).

Prognostic models with competing risks: methods and application to coronary risk prediction.

Clinical decision-making often relies on a subject's absolute risk of a disease event of interest. However, in a frail population, competing risk events may preclude the occurrence of the event of interest. We review competing-risk regression models with a view toward predictive modeling.

Common variants at ten loci influence QT interval duration in the QTGEN Study.

QT interval duration, reflecting myocardial repolarization on the electrocardiogram, is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study, as part of the QTGEN consortium. We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes.

Fetal and postnatal growth and body composition at 6 months of age.

Objectives: The objectives of the study was to examine which parental, fetal, and postnatal characteristics are associated with fat and lean mass at the age of 6 months and examine the effect of growth (catch-down, catch-up) in fetal life and early infancy on fat and lean mass.

Design: This study was embedded in the Generation R Study, a prospective cohort study from early fetal life onward. Body composition was measured by dual-energy X-ray absorptiometry in 252 infants at 6 months.

Calcium channel blockers, NOS1AP, and heart-rate-corrected QT prolongation.

Objectives: To study whether NOS1AP single nucleotide polymorphisms (SNPs), rs10494366 T>G and rs10918594 C>G, modify the heart-rate-corrected QT (QTc) prolonging effect of calcium channel blockers.

Background: Common variation in the NOS1AP gene has been associated with QT interval variation in several large population samples. NOS1 is presumed to influence intracellular calcium.

A high menaquinone intake reduces the incidence of coronary heart disease.

Background And Aim: Vitamin K dependent proteins have been demonstrated to inhibit vascular calcification. Data on the effect of vitamin K intake on coronary heart disease (CHD) risk, however, are scarce. To examine the relationship between dietary vitamins K(1) and K(2) intake, and its subtypes, and the incidence of CHD.