Publications by authors named "Peyser P"
Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.
View Article and Find Full Text PDFThe relationship between mitochondrial DNA (mtDNA) heteroplasmy and nuclear DNA (nDNA) methylation (CpGs) remains to be studied. We conducted an epigenome-wide association analysis of heteroplasmy burden scores across 10,986 participants (mean age 77, 63% women, and 54% non-White races/ethnicities) from seven population-based observational cohorts. We identified 412 CpGs (FDR p < 0.
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- Whole genome sequencing (WGS) helps identify rare genetic variants that may explain the missing heritability of coronary artery disease (CAD) by analyzing 4,949 cases and 17,494 controls from the NHLBI TOPMed program.
- The study estimates that the heritability of CAD is around 34.3%, with ultra-rare variants contributing about 50%, especially those with low linkage disequilibrium.
- Functional annotations show significant enrichment of CAD heritability, highlighting the importance of ultra-rare variants and specific regulatory mechanisms in different cells as major factors influencing genetic risk for the disease.
Article Synopsis
- * We found 17 genetic loci associated with sleep duration impacting lipid levels, with 10 of them being newly identified and linked to sleep-related disturbances in lipid metabolism.
- * The research points to potential drug targets that could lead to new treatments for lipid-related issues in individuals with sleep problems, highlighting the connection between sleep patterns and cardiovascular health.
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- Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
- Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
- The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
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- Clonal hematopoiesis (CH) occurs when genetically identical blood cells expand, often influenced by genetic mutations linked to blood cancers; however, many cases happen without known driver mutations.
- Researchers analyzed 51,399 genomes to study a specific type of CH (CH-LPMneg) without detectable leukemia-related mutations, developing a new method (GEM rate) to estimate mutation burden without paired samples.
- Through their study, they identified seven genes linked to CH-LPMneg and found that alterations in hematopoietic stem cell (HSC) behavior may drive this mutation burden, while a broader analysis revealed relationships between GEM and the expression of 404 genes.
Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes.
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- Coronary artery calcification (CAC) is linked to heart disease and assessed through a genome-wide association study (GWAS) involving 22,400 participants from various backgrounds.
- The study confirmed connections with four known genetic loci and discovered two new loci related to CAC, with supportive replication findings for both.
- Functional tests suggest that ARSE promotes calcification in vascular smooth muscle cells and its variants may influence CAC levels, identifying ARSE as a key target for potential treatments in vascular calcific diseases.
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- Genome-wide association studies (GWAS) have successfully identified genes linked to telomere length, but previous research hadn't validated these findings until now.
- In a large analysis involving over 211,000 people, the study discovered five new signals linked to telomere length and highlighted the importance of blood/immune cells in this area.
- The researchers confirmed that the genes KBTBD6 and POP5 truly affect telomere length by demonstrating that manipulating these genes can lengthen telomeres and that their regulation is crucial for understanding telomere biology.
Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.
View Article and Find Full Text PDFAlthough both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways.
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- This study analyzed the relationship between bone mineral density (BMD) and coronary artery calcification (CAC) using data from the Rotterdam Study and the Framingham Heart Study, involving a total of 3,647 individuals with detailed measurements of BMD and CAC.
- The researchers employed various statistical methods, including linear regression and Mendelian randomization, but found no significant associations between BMD levels and CAC.
- The results suggest that the earlier observed connections between low BMD and high CAC may not indicate a causal relationship but are likely influenced by other factors or shared underlying causes.
Article Synopsis
- Type 2 diabetes (T2D) is a complex disease influenced by various genetic factors and molecular mechanisms that vary by cell type and ancestry.
- In a large study involving over 2.5 million individuals, researchers identified 1,289 significant genetic associations linked to T2D, including 145 new loci not previously reported.
- The study categorized T2D signals into eight distinct clusters based on their connections to cardiometabolic traits and showed that these genetic profiles are linked to vascular complications, emphasizing the role of obesity-related processes across different ancestry groups.
Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotypes to identify quantitative trait loci for expression (eQTLs) and splicing (sQTLs) in coronary arteries from 138 ancestrally diverse Americans.
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- Educational attainment is linked to cardiovascular health, and a large genomic study examined how it interacts with cholesterol and triglyceride levels in nearly 226,315 individuals across five population groups.
- The study identified 18 new genetic variations related to lipid levels—nine for low-density lipoprotein (LDL), seven for high-density lipoprotein (HDL), and two for triglycerides (TG)—some of which interact with educational attainment.
- Researchers also found five gene targets that potentially interact with FDA-approved drugs, suggesting a connection between genetics and drug responses related to lipid metabolism and overall health.
Background: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.
Methods: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program.
Article Synopsis
- Large-scale whole-genome sequencing (WGS) studies have enhanced our understanding of how rare genetic variants affect complex human traits through better analysis techniques.* -
- Current methods for analyzing multiple traits are limited in their ability to handle rare variants in large WGS datasets, prompting the development of MultiSTAAR.* -
- MultiSTAAR enables more powerful analysis by considering relatedness, population structure, and the correlation between traits, leading to the discovery of new genetic associations in lipid traits that single-trait analyses missed.*
Article Synopsis
- Coronary artery disease (CAD) involves the buildup of atherosclerotic plaques in arteries, with complex interactions between vascular and immune cells contributing to its progression.
- This study integrates data from 22 single-cell RNA sequencing libraries, analyzing 118,578 cells to map human atherosclerosis and to better understand cell diversity and communication.
- Key findings include the identification of smooth muscle cell (SMC) markers linked to CAD and atherosclerosis progression, which were validated through various analyses, aiming to inform future cardiovascular research.
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- Megabase-scale mosaic chromosomal alterations (mCAs) in blood can indicate the risk of various human diseases, and this study analyzes whole-genome sequencing data from 67,390 individuals to better understand mCA rates across different genetic backgrounds.
- The research found that whole-genome sequencing is more effective than traditional methods for detecting mCAs, revealing that individuals of European ancestry have higher rates of autosomal mCAs and lower rates of chromosome X mCAs compared to those of African or Hispanic ancestry.
- The study identifies three genetic loci linked to chromosome X loss and associates rare variants in specific genes (DCPS, ADM17, PPP1R16B, and TET2) with autosomal mCAs
Article Synopsis
- * Findings validate previous associations, revealing that lower mtDNA CN correlates with a higher risk of coronary heart disease but within the context of no causal relationship established in either direction.
- * Strong evidence suggests that high low-density lipoprotein cholesterol influences mtDNA CN levels, indicating it may play a key role in the relationship between mtDNA CN and cardiovascular health.
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 avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population.
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- Nonalcoholic fatty liver disease (NAFLD) is widespread, partly genetic, and currently lacks effective treatment options.
- A genome-wide association study (GWAS) identified several genetic variants linked to NAFLD, focusing on genes related to metabolism and liver function.
- Genetic risk factors can help classify NAFLD into subtypes and significantly increase the risk of severe liver complications, potentially aiding in the development of targeted therapies.
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- The study investigates the role of CCR2, a receptor for CCL2 involved in monocyte movement, in the risk of atherosclerotic cardiovascular disease, particularly through examining genetic variants in a large population sample from the UK Biobank.
- Researchers identified 45 harmful genetic variants linked to lower monocyte counts, finding that carriers had a reduced risk of myocardial infarction and coronary artery disease, especially the M249K variant.
- The M249K variant was associated with significantly lower risks for heart issues without increasing infection risk, suggesting its potential protective role against cardiovascular diseases.
Article Synopsis
- This study examines the relationship between resting heart rate and cardiovascular diseases, identifying 493 genetic variants linked to this trait through a large-scale analysis of 835,465 individuals.
- It highlights the significance of higher genetically predicted resting heart rates, which are associated with an increased risk of dilated cardiomyopathy but lower risk for conditions like atrial fibrillation and ischemic strokes.
- The study also challenges previous findings on resting heart rate and all-cause mortality, suggesting earlier results may have been influenced by biases, ultimately enhancing our understanding of the biological implications of resting heart rate in cardiovascular health.