Patricia A. Peyser

cellSTAAR: Incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of non-coding regions

cellSTAAR integrates single-cell ATAC-seq with whole-genome sequencing to enhance power and interpretation of rare variant association tests in non-coding regions.

A statistical framework for powerful multi-trait rare variant analysis in large-scale whole-genome sequencing studies

The paper introduces MultiSTAAR, a statistical framework for multi-trait rare variant analysis in WGS studies, identifying new lipid trait associations in diverse populations.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood

The paper identifies genetic and phenotypic correlates of mosaic loss of chromosome Y in blood using whole genome sequencing data from the TOPMed program.

The Genetic Determinants and Genomic Consequences of Non-Leukemogenic Somatic Point Mutations

The paper develops a method to quantify somatic mutation burden in whole-genome sequencing data without paired-tissue samples and identifies genetic and phenotypic correlates of clonal hematopoiesis without known driver mutations.

Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis

This study performs a meta-analysis of scRNA-seq datasets to map human atherosclerosis cell diversity and identifies disease-relevant vascular cell states and markers.

Validation of human telomere length trans-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as novel human telomere length regulation genes

The paper validates novel telomere length regulation genes POP5 and KBTBD6 identified through trans-ancestry GWAS using functional experiments in blood cells.

Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors: evidence from a genome-wide association meta-analysis followed by Mendelian randomization

This study uses GWAS and Mendelian randomization to show that lower sclerostin levels increase risk of hypertension, type 2 diabetes, myocardial infarction, and atherogenic lipid profiles.

Clonal hematopoiesis is driven by aberrant activation of TCL1A

The paper develops PACER to infer clonal expansion rates from single timepoint data and identifies TCL1A activation as a mediator of clonal hematopoiesis fitness.

FHL5 controls vascular disease-associated gene programs in smooth muscle cells

This study identifies FHL5 as a causal gene for vascular disease risk through eQTL colocalization and functional analyses, showing its role in vascular remodeling and calcification.

Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus.

This study identifies 43 genomic loci associated with reproductive success in 785,604 individuals, showing ongoing natural selection at the FADS locus.

Structural variation across 138,134 samples in the TOPMed consortium

The paper presents a comprehensive catalog of structural variants across 138,134 individuals, identifying novel variants and their associations with cardio-metabolic and hematologic traits.

Mosaic chromosomal alterations in blood across ancestries via whole-genome sequencing

This study uses whole-genome sequencing to analyze mosaic chromosomal alterations across diverse ancestries, finding higher rates in certain populations and associations with germline variants.

A framework for detecting noncoding rare variant associations of large-scale whole-genome sequencing studies

The paper introduces a framework for detecting noncoding rare variant associations using whole-genome sequencing data, applying it to lipid traits in the TOPMed program.

Whole genome sequence analysis of blood lipid levels in >66,000 individuals

The paper performs whole genome sequence analysis of plasma lipid levels in 66,329 individuals, identifying new lipid-associated alleles, including rare non-coding variants.

Genomic and phenomic landscape of clonal hematopoiesis in over a million ancestrally diverse participants

This study analyzes clonal hematopoiesis in over a million diverse individuals, identifying 72 genome-wide significant loci and linking CHIP to various phenotypes.

Whole Genome Sequence Association Analysis of Fasting Glucose and Fasting Insulin Levels in Diverse Cohorts from the NHLBI TOPMed Program

The paper performs whole genome sequence association analysis of fasting glucose and insulin levels in diverse cohorts, identifying 22 significant variants across 16 gene regions, including rare variants.

Bidirectional Mendelian randomization supports bidirectional causality between telomere length and clonal hematopoiesis of intermediate potential

The paper uses bidirectional Mendelian randomization to show LTL lengthening increases CHIP risk, while CHIP accelerates LTL shortening, with modest mediation between CHIP and CAD via LTL.

A system for phenotype harmonization in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program

The paper describes a system for harmonizing phenotype data across multiple studies in the TOPMed program, enabling reproducible and shared phenotype data for over 80 studies.

Within-sibship GWAS improve estimates of direct genetic effects

In 159,701 siblings from 17 cohorts, population GWAS overstate direct effects on height, education, smoking, cognition, depressive symptoms and age at first birth; clinical traits mostly agree across models.

Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed

This study identifies 59 sentinel variants and two novel genes associated with telomere length using whole genome sequences from 109,122 trans-ethnic individuals.

Rare Non-coding Variation Identified by Large Scale Whole Genome Sequencing Reveals Unexplained Heritability of Type 2 Diabetes: Trans-Omics for Precision Medicine (TOPMed) Program

The paper identifies rare non-coding variants from whole genome sequencing in the TOPMed program, showing they contribute significantly to type 2 diabetes heritability.

Population sequencing data reveal a compendium of mutational processes in human germline

The paper decomposes mutation rate and spectra variation in human germline using blind source separation, identifying nine processes including those related to DNA damage and replication timing.

Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations

This study uses TOPMed whole genome sequences to improve imputation quality and detect rare variant associations in admixed African and Hispanic/Latino populations, identifying two novel associations with hematological traits.

Inherited Causes of Clonal Hematopoiesis of Indeterminate Potential in TOPMed Whole Genomes

The paper identifies germline genetic variants associated with clonal hematopoiesis of indeterminate potential (CHIP) using whole genome sequences from the TOPMed program.

Evaluation of the causal effect of fibrinogen on incident coronary heart disease via Mendelian randomization

This paper evaluates the causal effect of fibrinogen on coronary heart disease using Mendelian randomization, finding a small effect with multi-variant methods but not with single variant approaches.

Loss-of-function genomic variants with impact on liver-related blood traits highlight potential therapeutic targets for cardiovascular disease

The paper identifies loss-of-function variants affecting liver-related blood traits that reduce CVD risk without increasing metabolic disease risk, highlighting potential therapeutic targets.

Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile

The paper identifies 49 novel blood lipid loci associated with gene-sleep interactions in 126,926 individuals across 5 ancestry groups, with gene-short-sleep interactions explaining 4.25% of triglyceride variance.

Efficient variant set mixed model association tests for continuous and binary traits in large-scale whole genome sequencing studies

The paper introduces SMMAT, a variant-set mixed model association test for continuous and binary traits in large-scale WGS studies, showing it controls type I error rates and applies to population structured and related samples.

Fine-mapping of an expanded set of type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

This study fine-maps type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps, identifying 73 variants with >80% posterior probability of association.