Ramachandran Srini Vasan

TorchGWAS2: Cost-Effective Phenome- and Genome-Wide Association Testing in Related Samples

TorchGWAS2 improves genome-wide association testing in related samples by using a deterministic variance-correction algorithm, achieving faster and more powerful results across large-scale omics data.

Cross-cohort analysis of expression and splicing quantitative trait loci in TOPMed

The paper analyzes expression and splicing quantitative trait loci (e/sQTL) across multiple tissues in the TOPMed dataset and finds that secondary e/sQTL signals are still discoverable, with many GWAS signals colocalizing with these e/sQTL.

Plasma Proteomics and Sensitive Imaging Biomarkers of Vascular Brain Injury

The paper identifies plasma proteins associated with diffusion tensor imaging biomarkers of white matter injury and suggests potential causal relationships using Mendelian randomization.

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.

Human Plasma Proteomic Profile of Clonal Hematopoiesis

The paper identifies plasma proteins associated with clonal hematopoiesis and links them to cardiovascular disease through proteomic and genetic analyses.

Altered Gut Microbiota Mediates the Association between APOE Genotype and Amyloid-β Accumulation in Middle-Aged Adults

This study shows that gut microbiota mediates the effect of APOE ε4 genotype on amyloid-β accumulation in middle-aged adults.

Genetic Architecture and Analysis Practices of Circulating Metabolites in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program

The paper analyzes circulating metabolites using genome-wide association data from the TOPMed program, identifying 1,778 loci and highlighting sex-specific genetic contributions.

Adherence to Lifes Essential 8 Enhances Gut Microbiota Diversity and Cognitive Performance

This study shows that better adherence to LE8 metrics improves gut microbiota diversity and cognitive performance in the Framingham Heart Study participants.

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.

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.

Cerebral Small Vessel Disease Burden is Associated with Decreased Abundance of Gut Barnesiella intestinihominis Bacterium in the Framingham Heart Study

The paper investigates the relationship between gut microbiota and cerebral small vessel disease markers in the Framingham Heart Study, finding associations between specific bacterial genera and cSVD burden.

Genetic modification of inflammation and clonal hematopoiesis-associated cardiovascular risk

The paper identifies IL1RAP and AIM2 as key modifiers of CHIP-associated cardiovascular risk using UK Biobank data and CRISPR experiments in mice.

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.

Genetic control of mRNA splicing as a potential mechanism for incomplete penetrance of rare coding variants

This study shows that common splice-regulatory variants can reduce the pathogenicity of rare exonic variants by modulating mRNA splicing.

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.

Investigating gene-diet interactions impacting the association between macronutrient intake and glycemic traits

The paper identifies a gene-diet interaction modifying the association between macronutrient intake and glycemic traits, highlighting challenges in detecting such interactions due to measurement error and sample size.

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.

Deep learning enables genetic analysis of the human thoracic aorta

This study uses deep learning to analyze aortic dimensions from MRI and identifies genetic loci associated with aortic diameter, highlighting SVIL as a key gene and developing a polygenic score for aneurysm risk.

Genetic and environmental correlations between complex phenotypes differ by race/ethnicity and sex

The paper estimates genetic and environmental correlations between complex phenotypes across different racial/ethnic groups and sexes using data from the TOPMed program.

Presence and Transmission of Mitochondrial Heteroplasmic Mutations in Human Populations of European and African Ancestry

The paper examines the concordance and characteristics of mitochondrial heteroplasmic mutations in maternal pairs of European and African ancestry, finding higher concordance in close relatives and associations with age and nuclear genome regions.

BinomiRare: A carriers-only test for association of rare genetic variants with a binary outcome for mixed models and any case-control proportion

The paper introduces BinomiRare, a test for rare variant association with binary outcomes in mixed models, showing it controls type 1 error in simulations and applies it to study genetic variants in disease traits.

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.

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.

De novo mutations across 1,465 diverse genomes reveal novel mutational insights and reductions in the Amish founder population.

The paper analyzes de novo mutations in 1,465 genomes to show similar mutation rates across ancestries but reduced rates in the Amish population, with environmental factors possibly influencing mutation rates.