Robert E. Handsaker

Somatic DNA-repeat expansions initiate distinct yet analogous changes in Huntington's disease cortical and striatal neurons

This study shows that somatic DNA-repeat expansions in cortical and striatal neurons of Huntington's disease initiate similar pathological changes, but lead to distinct gene expression outcomes.

Human and bacterial genetic variation shape oral microbiomes and health

The paper identifies 11 human genetic loci associated with oral microbiome composition and host-microbial interactions linked to tooth decay.

Insights into the causes and consequences of DNA repeat expansions from 700,000 biobank participants

The paper analyzes DNA repeat instability in 700,000 participants to identify genetic modifiers of repeat expansion and contraction rates and their clinical associations.

Long somatic DNA-repeat expansion drives neurodegeneration in Huntington disease

The paper shows that HTT CAG repeats expand in striatal neurons over time, leading to gene expression changes and neurodegeneration in Huntington disease.

Concerted neuron-astrocyte gene expression declines in aging and schizophrenia

The paper identifies a neuron-astrocyte gene expression program, SNAP, that declines in aging and schizophrenia, linking it to cognitive function and genetic risk factors.

Utility of long-read sequencing for All of Us

The paper compares short-read and long-read sequencing in the All of Us initiative, finding HiFi reads provide the most accurate variant calling and presents a cloud-based pipeline for long-read analysis.

Hidden protein-altering variants influence diverse human phenotypes

The paper identifies protein-altering structural variants in UK Biobank data and finds associations with various quantitative traits, including hypertension and type 2 diabetes risk.

Repeat polymorphisms in non-coding DNA underlie top genetic risk loci for glaucoma and colorectal cancer.

The paper identifies non-coding VNTRs associated with glaucoma and colorectal cancer risk using UK Biobank data and statistical imputation.

The Genetic Architecture of DNA Replication Timing in Human Pluripotent Stem Cells

This study identifies genetic regulators of DNA replication timing in human pluripotent stem cells, revealing a histone code and combinatorial regulatory mechanisms.

Protein-coding repeat polymorphisms strongly shape diverse human phenotypes

The paper estimates VNTR lengths from whole-exome sequencing data and identifies associations between VNTRs and human phenotypes, finding strong effects on traits like height and lipoprotein(a).

Biological insights from the whole genome analysis of human embryonic stem cells

This study performs whole genome sequencing of human embryonic stem cells to identify genetic variants and provides resources for cell line selection.

A vast resource of allelic expression data spanning human tissues

The paper presents a large ASE resource from GTEx v8 with 431 million SNP-level and 153 million haplotype-level measurements, and extends phASER to estimate cis regulatory variant effect sizes.

Cell type specific genetic regulation of gene expression across human tissues

The paper uses bulk RNA-seq data to estimate cell type abundances and identifies cell type interaction QTLs that provide finer resolution of tissue specificity than bulk cis-eQTLs.

Determinants of telomere length across human tissues

The paper examines telomere length variation across 6,391 tissue samples from 952 individuals, showing tissue-specific differences, positive correlations between tissues, and associations with age and ancestry.

Diverse transcriptomic signatures across human tissues identify functional rare genetic variation

Integrating expression, allelic expression and splicing across tissues identifies rare variants with relevance to traits.

A Quantitative Proteome Map of the Human Body

The paper quantifies protein levels across 32 human tissues and compares them to transcriptome data, revealing insights into post-transcriptional regulation and disease mechanisms.

Insights into dispersed duplications and complex structural mutations from whole genome sequencing 706 families

The paper identifies dispersed duplications and de novo structural mutations using whole-genome sequencing data from 706 families by analyzing IBD relationships and copy number variations.

Mapping genetic effects on cellular phenotypes with "cell villages"

Census-seq pools cells from >100 human donors into "cell villages" and quantifies donor DNA before and after selection to map genetic effects on cellular traits.

The GTEx Consortium atlas of genetic regulatory effects across human tissues

GTEx v8 maps expression and splicing QTLs in 49 tissues from 838 donors: cis-eQTLs cover 94.7% of protein-coding genes, and cross-tissue QTL sharing mirrors cell-type composition.

Complement component 4 genes contribute sex-specific vulnerability in diverse illnesses

This study identifies C4 genes in the MHC locus as sex-specific contributors to risk for lupus, Sjogrens syndrome, and schizophrenia, with stronger effects in men than women.

Multi-platform discovery of haplotype-resolved structural variation in human genomes

This study identifies a large number of structural variants in human genomes using multiple sequencing technologies and presents them as a gold standard for future studies.

Limited contribution of rare, noncoding variation to autism spectrum disorder from sequencing of 2,076 genomes in quartet families

This study examines the role of noncoding variation in autism spectrum disorder using whole genome sequencing of 2,076 genomes, finding no significant association after correction for multiple testing.

The Genetic Landscape of Diamond-Blackfan Anemia

This study identifies genetic mutations in 78% of Diamond-Blackfan anemia patients using whole exome sequencing, finds new RP genes, and reports genotype-phenotype associations.

Integrated Clinical and Omics Approach to Rare Diseases: Novel Genes and Oligogenic Inheritance in Holoprosencephaly

This study identifies novel HPE genes and oligogenic inheritance patterns in holoprosencephaly by integrating clinical data with exome sequencing and gene prioritization.

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries

The paper uses whole genome sequencing to identify genetic variants associated with plasma lipoprotein(a) levels and finds high heritability and inter-ethnic differences in Lp(a) risk.

Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics

The paper develops S-PrediXcan to compute gene expression associations from GWAS summary data and applies it to 44 GTEx tissues and 100+ phenotypes, finding tissue-specific effects and colocalized associations.

Whole Genome Sequencing in Psychiatric Disorders: the WGSPD Consortium

The paper discusses the role of whole genome sequencing in psychiatric disorders through the WGSPD consortium, aiming to assess its utility compared to other genotyping methods.