Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9).

Post-mortem CT findings following intentional ingestion of mercuric chloride.

Mercury is known to be associated with both acute and chronic poisoning. A 36-year-old man intentionally ingested mercuric chloride (HgCl(2)) and died within 24h. Post-mortem CT images showed oral, esophageal and gastric wall hyperdense "staining".

Variants in the CNR1 and the FAAH genes and adiposity traits in the community.

Pharmacologic blockade of the endocannabinoid receptor 1 leads to weight loss and an improved metabolic risk profile in overweight and obese individuals. We hypothesize that common genetic variants in the CNR1 (encoding endocannabinoid receptor 1) and FAAH genes (encoding fatty acid amide hydrolase, a key enzyme hydrolyzing endocannabinoids) are associated with adiposity traits. We genotyped 18 single-nucleotide polymorphisms (SNPs) in the CNR1 gene and 9 SNPs in the FAAH gene in 2,415 Framingham Offspring Study participants (mean age 61 +/- 10 years; 52.

An open access database of genome-wide association results.

Background: The number of genome-wide association studies (GWAS) is growing rapidly leading to the discovery and replication of many new disease loci. Combining results from multiple GWAS datasets may potentially strengthen previous conclusions and suggest new disease loci, pathways or pleiotropic genes. However, no database or centralized resource currently exists that contains anywhere near the full scope of GWAS results.

Novel measurements of periaortic adipose tissue in comparison to anthropometric measures of obesity, and abdominal adipose tissue.

Background: Perivascular adipose tissue may be associated with the amount of local atherosclerosis. We developed a novel and reproducible method to standardize volumetric quantification of periaortic adipose tissue by computed tomography (CT) and determined the association with anthropometric measures of obesity, and abdominal adipose tissue.

Methods: Measurements of adipose tissue were performed in a random subset of participants from the Framingham Heart Study (n=100) who underwent multidetector CT of the thorax (ECG triggering, 2.

Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study.

Aims: The aim of this study was to assess whether pericardial fat, intrathoracic fat, and visceral abdominal adipose tissue (VAT) are associated with the prevalence of cardiovascular disease (CVD).

Methods And Results: Participants from the Framingham Heart Study Offspring cohort underwent abdominal and chest multidetector computed tomography to quantify volumes of pericardial fat, intrathoracic fat, and VAT. Relations between each fat depot and CVD were assessed using logistic regression.

Relation of corneal arcus to cardiovascular disease (from the Framingham Heart Study data set).

Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary artery disease (CAD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and CAD.

Synthetic approaches to the 2007 new drugs.

New drugs are introduced to the market every year and each individual drug represents a privileged structure for its biological target. These new chemical entities (NCEs) provide insights into molecular recognition and also serve as leads for designing future new drugs. This review covers the syntheses of 19 NCEs marketed in 2007.

Patterns of abdominal fat distribution: the Framingham Heart Study.

Objective: The prevalence of abdominal obesity exceeds that of general obesity. We sought to determine the prevalence of abdominal subcutaneous and visceral obesity and to characterize the different patterns of fat distribution in a community-based sample.

Research Design And Methods: Participants from the Framingham Heart Study (n = 3,348, 48% women, mean age 52 years) underwent multidetector computed tomography; subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were assessed.

Association of lifestyle factors with abdominal subcutaneous and visceral adiposity: the Framingham Heart Study.

Objective: The purpose of this study was to assess the relationship between lifestyle factors and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based setting.

Research Design And Methods: Cross-sectional associations between lifestyle factors (dietary quality, physical activity, smoking, and alcohol consumption) and SAT and VAT volumes were examined in 2,926 Framingham Heart Study participants (48.6% women, aged 50 +/- 10 years).

Common variants at 30 loci contribute to polygenic dyslipidemia.

Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time.

Von Willebrand factor, type 2 diabetes mellitus, and risk of cardiovascular disease: the framingham offspring study.

Background: Von Willebrand factor (vWF) is inconsistently associated with cardiovascular disease (CVD). This might be explained by associations of vWF with type 2 diabetes mellitus and insulin resistance.

Methods And Results: We tested whether vWF predicted incident CVD in 3799 Framingham Offspring Study participants, and in particular, among those with type 2 diabetes mellitus or insulin resistance.

Genetics of the Framingham Heart Study population.

This chapter provides an introduction to the Framingham Heart Study and the genetic research related to cardiovascular diseases conducted in this unique population. It briefly describes the origins of the study, the risk factors that contribute to heart disease, and the approaches taken to discover the genetic basis of some of these risk factors. The genetic architecture of several biological risk factors has been explained using family studies, segregation analysis, heritability, and phenotypic and genetic correlations.

SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMap.

Summary: The interpretation of genome-wide association results is confounded by linkage disequilibrium between nearby alleles. We have developed a flexible bioinformatics query tool for single-nucleotide polymorphisms (SNPs) to identify and to annotate nearby SNPs in linkage disequilibrium (proxies) based on HapMap. By offering functionality to generate graphical plots for these data, the SNAP server will facilitate interpretation and comparison of genome-wide association study results, and the design of fine-mapping experiments (by delineating genomic regions harboring associated variants and their proxies).

Defining normal distributions of coronary artery calcium in women and men (from the Framingham Heart Study).

Coronary artery calcium (CAC) may improve risk stratification for patients with coronary heart disease (CHD) beyond traditional risk factors. Subjects from the Framingham Heart Study Offspring and Third Generation cohorts (48% women; mean age 53 years) underwent noncontrast electrocardiographically triggered cardiac multidetector computed tomography. The prevalence of absolute CAC (Agatston score [AS] >0, >100, and >400) and relative age- and gender-specific strata (25th, 50th, 75th, 90th, and 95th percentiles) were determined in a healthy subset free of clinically apparent cardiovascular disease or CHD risk factors (n = 1,586), the overall sample at risk (n = 3,238), and subjects at intermediate Framingham risk score (FRS; 6% to 20% 10-year CHD event risk; n = 1,177).

Facet joint osteoarthritis and low back pain in the community-based population.

Study Design: Cross-sectional study.

Objective: To evaluate the association between lumbar spine facet joint osteoarthritis (FJ OA) identified by multidetector computed tomography (CT) and low back pain (LBP) in the community-based Framingham Heart Study.

Summary Of Background Data: The association between lumbar FJ OA and LBP remains unclear.

Cardiovascular genomics, personalized medicine, and the National Heart, Lung, and Blood Institute: part I: the beginning of an era.

The inaugural issue of Circulation: Cardiovascular Genetics arrives at a remarkable time in the history of genetic research and cardiovascular medicine. Despite tremendous progress in knowledge gained, cardiovascular disease(CVD) remains the leading cause of death in the United States,1 and it has overcome infectious diseases as the leading cause of death worldwide.2 In addition, rates of CVD remain higher in black and Hispanic populations in the United States.

Association of visceral and subcutaneous adiposity with kidney function.

Background And Objectives: Obesity is a risk factor for incident chronic kidney disease (CKD). Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations.

Common variants in the adiponectin gene (ADIPOQ) associated with plasma adiponectin levels, type 2 diabetes, and diabetes-related quantitative traits: the Framingham Offspring Study.

Objective: Variants in ADIPOQ have been inconsistently associated with adiponectin levels or diabetes. Using comprehensive linkage disequilibrium mapping, we genotyped single nucleotide polymorphisms (SNPs) in ADIPOQ to evaluate the association of common variants with adiponectin levels and risk of diabetes.

Research Design And Methods: Participants in the Framingham Offspring Study (n = 2,543, 53% women) were measured for glycemic phenotypes and incident diabetes over 28 years of follow-up; adiponectin levels were quantified at exam 7.

Vitamin K, circulating cytokines, and bone mineral density in older men and women.

Background: Vitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro.

Objective: The objective of this study was to assess 1) associations between measures of vitamin K status [plasma phylloquinone and serum percentage of undercarboxylated osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP) concentrations and 2) the effect of daily 500 mug phylloquinone supplementation for 3 y on cytokine concentrations.

Design: Concentrations of IL-6, osteoprotegerin, and CRP and bone mineral density (BMD) were measured at baseline and after 3 y of follow-up in 379 healthy men and women (60-81 y; 58.

Indexes of kidney function and coronary artery and abdominal aortic calcium (from the Framingham Offspring Study).

It is uncertain whether moderate chronic kidney disease (CKD) or measures of kidney function are associated with subclinical atherosclerosis as represented by coronary artery calcium (CAC) or abdominal aortic calcium (AAC). We used logistic and linear regression analyses to relate CKD (glomerular filtration rate <60 ml/min/1.73 m(2)), cystatin C (cysC), and microalbuminuria (MA) with CAC and AAC obtained using multidetector computed tomography in Framingham Heart Study Offspring participants (mean age 59 years, 55.

Cerebrovascular disease in type 1A glycogen storage disease.

Glycogen storage diseases are a group of genetic disorders involving pathways for storage of glycogen and its utilization to maintain blood glucose. Clinical manifestations include hypoglycaemia, hepatomegaly, delayed adolescence and hyperlipidaemia. Hyperlipidaemia is frequent and patients surviving long enough are thought to be at increased risk of atherosclerosis.

Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study.

Background And Purpose: Previous estimates of the prevalence of silent cerebral infarction (SCI) on MRI in community-based samples have varied between 5.8% and 17.7% depending on age, ethnicity, presence of comorbidities, and imaging techniques.

Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study.

Background And Aims: Fatty liver is the hepatic manifestation of obesity, but community-based assessment of fatty liver among unselected patients is limited. We sought to determine the feasibility of and optimal protocol for quantifying fat content in the liver in the Framingham Heart Study using multidetector computed tomography (MDCT) scanning.

Methods: Participants (n = 100, 49% women, mean age 59.