Sharon L. R. Kardia

A reference panel for linkage disequilibrium and genotype imputation using whole-genome sequencing data from 2,680 participants across India

The paper constructs a large-scale LD and genotype imputation reference panel using whole-genome sequencing data from 2,680 Indian participants, improving imputation accuracy and polygenic risk score performance.

Revisiting the Evolution of Lactase Persistence: Insights from South Asian Genomes

This study analyzes South Asian genomes to understand the evolutionary history of lactase persistence, finding that Steppe ancestry, not selection, explains most LP prevalence, with exceptions in two pastoralist groups.

Genome-wide association study provides novel insight into the genetic architecture of severe obesity.

This study identifies novel genetic signals associated with severe obesity through GWAS and shows strong genetic overlap with BMI, highlighting shared comorbidities and lifestyle interactions.

Whole genome sequence association analysis of brain structural volume measures in the NHLBI TOPMed Program highlights novel loci in diverse participants

This study uses whole-genome sequence data from diverse participants to identify novel genetic loci associated with brain structural volumes, highlighting the importance of diverse cohorts in uncovering genetic architecture.

Region-based analysis with functional annotation identifies genes associated with cognitive function in South Asians from India

The paper identifies AD-associated genes in South Asians using whole-genome sequence data and variant analysis, finding associations for APOE, PICALM, and TSPOAP1 with cognitive function.

Multi-ancestry transcriptome-wide association studies of cognitive function, white matter hyperintensity, and Alzheimer's disease

This paper conducts multi-ancestry transcriptome-wide association studies to identify genes associated with cognitive function, white matter hyperintensity, and Alzheimer's disease using gene expression data from European and African ancestry individuals.

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.

Effect of APOE e4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD

The paper examines the effect of APOE ε4 and its interaction with sociodemographic factors on cognitive measures in South Asians from LASI-DAD, finding stronger associations in older adults and females.

Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed Whole Genome Sequencing Study

The paper identifies 83 rare lncRNA variant sets associated with blood lipid levels using WGS data from the TOPMed program and validates some in UK Biobank data.

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.

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.

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.

Exome Array Analysis of 9,721 ischemic stroke cases from the SiGN Consortium

The paper analyzes exome array data from 9,721 ischemic stroke cases to identify coding variants associated with stroke, finding 15 significant variants, including 13 novel associations.

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.

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.

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.

Recovery of trait heritability from whole genome sequence data

The paper estimates heritability for height and BMI using whole-genome sequence data and finds that rare variants contribute significantly to the missing heritability.

Rare coding variants in 35 genes associate with circulating lipid levels: a multi-ancestry analysis of 170,000 exomes

This study identifies 35 genes associated with circulating lipid levels using rare coding variants from 170,000 exomes across multiple ancestries.

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.

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

Over 400 million variants, 97% below 1% frequency, emerge from deep whole-genome sequencing of 53,831 diverse TOPMed participants; TOPMed haplotypes enable imputation down to ~0.01% frequency.

Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing

This study identifies 137 genome-wide significant loci associated with DNA methylation biomarkers of ageing using DNAm and SNP data from over 41,000 individuals.

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.

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.

Exome chip meta-analysis elucidates the genetic architecture of rare coding variants in smoking and drinking behavior

The paper analyzes rare coding variants in smoking and drinking behavior using exome chip data, finding that they contribute to phenotypic variation but require larger samples for individual variant associations.

Ninety-nine independent genetic loci influencing general cognitive function include genes associated with brain health and structure (N = 280,360)

This study identifies 99 genetic loci associated with general cognitive function using data from 280,360 individuals, finding genes linked to brain structure and neurodegenerative disorders.