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22 papers found.
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Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust...

Sequence Analysis of Six Blood Pressure Candidate Regions in 4,178 Individuals: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study

Background Genome-wide association studies (GWAS) identified multiple loci for blood pressure (BP) and hypertension. Six genes – ATP2B1, CACNB2, CYP17A1, JAG1, PLEKHA7, and SH2B3 – were evaluated for sequence variation with large effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP). Methods and Results...

Genetic Evidence for a Normal-Weight “Metabolically Obese” Phenotype Linking Insulin Resistance, Hypertension, Coronary Artery Disease, and Type 2 Diabetes

Yaghootkar Robert A. Scott Charles C. White Weihua Zhang Elizabeth Speliotes Patricia B. Munroe Georg B. Ehret Joshua C. Bis Caroline S. Fox Mark Walker Ingrid B. Borecki Joshua W. Knowles Laura Yerges

Prospective Associations of Coronary Heart Disease Loci in African Americans Using the MetaboChip: The PAGE Study

Background Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in...

The Challenges of Genome-Wide Interaction Studies: Lessons to Learn from the Analysis of HDL Blood Levels

Genome-wide association studies (GWAS) have revealed 74 single nucleotide polymorphisms (SNPs) associated with high-density lipoprotein cholesterol (HDL) blood levels. This study is, to our knowledge, the first genome-wide interaction study (GWIS) to identify SNP×SNP interactions associated with HDL levels. We performed a GWIS in the Rotterdam Study (RS) cohort I (RS-I) using the...

Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades...

Associations of NINJ2 Sequence Variants with Incident Ischemic Stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) Consortium

Background Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident...

Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci

, and SH2B3 Loci Guillaume Pare Paul M Ridker Lynda Rose Maja Barbalic Jose e Dupuis Abbas Dehghan Joshua C. Bis Emelia J. Benjamin Dov Shiffman Alexander N. Parker Daniel I. Chasman Michel Georges

Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including...

A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach

Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger...

Logic Regression for Analysis of the Association between Genetic Variation in the Renin-Angiotensin System and Myocardial Infarction or Stroke

Recent developments in genetic sequencing technology now make it possible to genotype large numbers of single nucleotide polymorphisms (SNPs) in large samples. Many association studies using SNP data are now being carried out. Typically, these observational studies establish whether certain haplotypes or individual SNPs are associated with a health outcome. Few methods exist for...

Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium

Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers...

Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia

Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the...

Renin-Angiotensin System Haplotypes and the Risk of Myocardial Infarction and Stroke in Pharmacologically Treated Hypertensive Patients

The products of the renin-angiotensin system (RAS) play an important role in the pathogenesis of cardiovascular disease. Studies examining RAS gene variants and cardiovascular disease have focused on single-nucleotide polymorphisms (SNPs) rather than haplotypes, which better characterize the patterns of genetic variation. The authors conducted a population-based, case-control...

Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans

James S. Pankow Candace Kammerer Yongmei Liu Michael Nalls Sarah Tishkoff Fridtjof Thomas Elad Ziv Bruce M. Psaty Joshua C. Bis Jerome I. Rotter Kent D. Taylor Erin Smith Nicholas J. Schork Daniel Levy

No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index: Results from Meta-Analyses of 80,607 Subjects

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations...

Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium

Tang Ani Manichaikul Millennia Foy Edmond K. Kabagambe Jennifer A. Nettleton Irena B. King Lu-Chen Weng Sayanti Bhattacharya Stefania Bandinelli Joshua C. Bis Stephen S. Rich David R. Jacobs Jr. Antonio

Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels

Maja Barbalic 15 Jose e Dupuis 12 9 Abbas Dehghan 16 20 Joshua C. Bis 19 Ron C. Hoogeveen 7 Renate B. Schnabel 12 Vijay Nambi 7 Monique Bretler 16 20 Nicholas L. Smith 8 16 Annette Peters 5 Chen Lu

Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations

Michael Preuss CARDIoGRAM Consortium Joshua C. Bis Christopher J. O'Donnell Nora Franceschini CHARGE Consortium Jacqueline C. M. Witteman Tatiana Axenovich Ben A. Oostra Thomas Meitinger Andrew A. Hicks

Genetic variation associated with circulating monocyte count in the eMERGE Network

J.A. van Rooij Ming-Huei Chen Albert V. Smith Neil A. Zakai Qiong Yango Melissa Garcia Yongmei Liu Thomas Lumley Aaron R. Folsom Alex P. Reiner Janine F. Felix Abbas Dehghan James G. Wilson Joshua C ... . Bis Caroline S. Fox Nicole L. Glazer L. Adrienne Cupples Josef Coresh Gudny Eiriksdottir Vilmundur Gudnason Stefania Bandinelli Timothy M. Frayling Aravinda Chakravarti Cornelia M. van Duijn David