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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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Article
Open AccessValidation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes
Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere le...
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Article
Lac-Phe mediates the effects of metformin on food intake and body weight
Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin’s effects on energy balance. Here, we show that metfor...
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Article
Open AccessGenetic drivers of heterogeneity in type 2 diabetes pathophysiology
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic c...
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Article
Open AccessX-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements
X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association met...
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Article
Open AccessGenome-wide association identifies novel ROP risk loci in a multiethnic cohort
We conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide...
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Article
Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification
Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study of CAC in 22,400 p...
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Article
Open AccessMosaic chromosomal alterations in blood across ancestries using whole-genome sequencing
Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analy...
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Article
Open AccessMulti-ancestry epigenome-wide analyses identify methylated sites associated with aortic augmentation index in TOPMed MESA
Despite the prognostic value of arterial stiffness (AS) and pulsatile hemodynamics (PH) for cardiovascular morbidity and mortality, epigenetic modifications that contribute to AS/PH remain unknown. To gain a b...
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Article
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
Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification
Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic a...
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Article
Open AccessGenetic insights into resting heart rate and its role in cardiovascular disease
Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associate...
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Article
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin ac...
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Article
Open AccessMetabolomic profiling of glucose homeostasis in African Americans: the Insulin Resistance Atherosclerosis Family Study (IRAS-FS)
African Americans are at increased risk for type 2 diabetes.
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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
Open AccessMulti-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing
Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, who...
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Article
Gene expression associations with body mass index in the Multi-Ethnic Study of Atherosclerosis
Obesity, defined as excessive fat accumulation that represents a health risk, is increasing in adults and children, reaching global epidemic proportions. Body mass index (BMI) correlates with body fat and futu...
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Article
Open AccessDistinct COPD subtypes in former smokers revealed by gene network perturbation analysis
Chronic obstructive pulmonary disease (COPD) varies significantly in symptomatic and physiologic presentation. Identifying disease subtypes from molecular data, collected from easily accessible blood samples, ...
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Article
Open AccessSecretory leukocyte protease inhibitor and risk of heart failure in the Multi-Ethnic Study of Atherosclerosis
Circulating protease inhibitors are important regulators of inflammation that are implicated in the pathophysiology of heart failure (HF). Secretory leukocyte protease inhibitor (SLPI) is a serine protease inh...
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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...
