Erik P.A. van Iperen

The Dutch cardiomyopathy registry (DCR); rationale and registry design

Peter-Paul Zwetsloot, Michiel T.H.M. Henkens, Erik P.A. van Iperen, Michiel Minten et autres

BACKGROUND: Cardiomyopathies are important causes of arrhythmias, sudden cardiac death, and heart failure. With accumulating knowledge in clinical, genetic, and molecular phenotyping, the number of distinct disease entities is growing. There is a need for broad, inclusive, high-quality prospective multi-center registries to …

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Clinical presentation, disease course, and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease: a cohort study across 18 countries

Marijke Linschoten, Alicia Uijl, Astrid Schut, C E M Jakob et autres

AIMS: Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. METHODS AND RESULTS: We used data …

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Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

Toby Johnson, Amar Mehta, Nathan Pankratz, Mohammad Hadi Zafarmand et autres

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of …

Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Sandosh Padmanabhan, Matthijs F.L. Meijs, Yiran Guo, Amber L. Beitelshees et autres

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by …

Mendelian randomization of blood lipids for coronary heart disease

Susan Redline, Reecha Sofat, Sonia Shah, Suthesh Sivapalaratnam et autres

AimsTo investigate the causal role of high-density lipoprotein cholesterol (HDL-C) and triglycerides in coronary heart disease (CHD) using multiple instrumental variables for Mendelian randomization.Methods and resultsWe developed weighted allele scores based on single nucleotide polymorphisms (SNPs) with established associations with HDL-C, triglycerides, …

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A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

N. Charlotte Onland‐Moret, Suthesh Sivapalaratnam, Patricia B. Munroe, Mark J. Caulfield et autres

To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome.

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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Markku Laakso, Marcus E. Kleber, Yun Kyoung Kim, Peter E. H. Schwarz et autres

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified …

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Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis

Suthesh Sivapalaratnam, Zabaneh, Erik P.A. van Iperen, Hypponen et autres

BACKGROUND: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. METHODS: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated …

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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis

Eleanor Wheeler, Aaron Leong, Ching‐Ti Liu, Marie‐France Hivert et autres

BACKGROUND: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action …

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Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals

Emily Holzinger, Shefali S. Verma, Carrie Moore, Molly A. Hall et autres

The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), …

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Extending the use of GWAS data by combining data from different genetic platforms

Erik P.A. van Iperen, G. Kees Hovingh, Folkert W. Asselbergs, Aeilko H. Zwinderman

BACKGROUND: In the past decade many Genome-wide Association Studies (GWAS) were performed that discovered new associations between single-nucleotide polymorphisms (SNPs) and various phenotypes. Imputation methods are widely used in GWAS. They facilitate the phenotype association with variants that are not directly genotyped. …

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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Georg Ehret, Teresa Ferreira, Daniel I. Chasman, Ellen M. Schmidt et autres

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We …