64 Result(s)
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Jeffrey R O'Connell
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Article
Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate
Clonal hematopoiesis of indeterminate potential (CHIP), whereby somatic mutations in hematopoietic stem cells confer a selective advantage and drive clonal expansion, not only correlates with age but also conf...
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Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease
Nonalcoholic fatty liver disease (NAFLD) is common and partially heritable and has no effective treatments. We carried out a genome-wide association study (GWAS) meta-analysis of imaging (n = 66,814) and diagnost...
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Article
Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis
Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2–6, but the basis of their fi...
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Article
Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies
Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with c...
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A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies
Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV ass...
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Open AccessWhole genome sequence analysis of blood lipid levels in >66,000 individuals
Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated allel...
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Article
Open AccessGenetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are ...
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Open AccessWhole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage who...
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Open AccessAn Amish founder population reveals rare-population genetic determinants of the human lipidome
Identifying the genetic determinants of inter-individual variation in lipid species (lipidome) may provide deeper understanding and additional insight into the mechanistic effect of complex lipidomic pathways ...
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Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring
A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferati...
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Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data
Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. ...
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Article
Open AccessGenome sequencing unveils a regulatory landscape of platelet reactivity
Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through...
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Open AccessVariant-specific inflation factors for assessing population stratification at the phenotypic variance level
In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differe...
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Article
The trans-ancestral genomic architecture of glycemic traits
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregate...
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Article
Open AccessChromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now ana...
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Open AccessSequencing of 53,831 diverse genomes from the NHLBI TOPMed Program
The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treat...
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Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale
Large-scale whole-genome sequencing studies have enabled the analysis of rare variants (RVs) associated with complex phenotypes. Commonly used RV association tests have limited scope to leverage variant functi...
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Article
Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 indivi...
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Article
Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conduc...
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 22...
