John Brent Richards

Polygenic prediction of treatment response for precision medicine is vulnerable to collider bias

This paper shows that polygenic risk scores for CAD can create false treatment response patterns due to collider bias, not actual biological effects.

Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection in hospitalized COVID-19 patients

This study identifies gene-environment interactions influencing immune response to SARS-CoV-2 in hospitalized patients using single-cell RNA-sequencing and eQTL analysis.

The transaminase-omega-amidase pathway is a redox switch in glutamine metabolism that generates alpha-ketoglutarate

The paper identifies the transaminase-omega-amidase pathway as a redox-sensitive metabolic switch in endothelial glutamine metabolism, showing that NIT2 oxidation inhibits its activity and affects angiogenesis.

A flexible pipeline for reproducible exome-wide rare variant gene-trait associations

The paper introduces a customizable pipeline for exome-wide rare variant gene-trait associations, demonstrating its utility by replicating three studies and providing a standardized framework for similar analyses.

Caution when using network partners for target identification in drug discovery

The paper tests using protein network partners to identify drug targets, finding that while sensitivity improves, precision is low, limiting practical application.

An accurate genetic colocalization method for the HLA locus

This paper introduces HLA-colocalization, a method for genetic colocalization at the HLA locus using HLA alleles, showing it identifies novel causal associations between viruses and autoimmune diseases.

Identifying therapeutic targets for cancer: 2,094 circulating proteins and risk of nine cancers

This study identifies 40 circulating proteins associated with cancer risk using MR and colocalization, highlighting potential therapeutic targets and adverse effects of protein-altering interventions.

The performance of AlphaMissense to identify genes causing disease

This study evaluates AlphaMissense's impact on gene-based testing for disease causation using UK Biobank exome data, finding no significant improvement in identifying disease-causing genes.

Alternative splicing in the lung influences COVID-19 severity and respiratory diseases.

This study identifies alternative splicing in lung genes as a factor influencing COVID-19 severity and respiratory diseases using Mendelian randomization.

Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants

The paper identifies HLA variants associated with HBV vaccine response in Bangladeshi infants and links them to vaccine escape mechanisms.

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

The paper identifies nephronectin as a mediator of obesity's effect on COVID-19 severity using proteome-wide Mendelian randomization and validates its expression in lung cells.

HLA allele-calling using whole-exome sequencing identifies 129 novel associations in 11 autoimmune diseases: a multi-ancestry analysis in the UK Biobank

This study uses whole-exome sequencing to directly call HLA alleles in the UK Biobank, identifying 129 novel associations between HLA alleles and 11 autoimmune diseases.

ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19

This study identifies ELF5 as a risk gene for severe COVID-19 using genetic and single-cell expression data, showing its specific expression in respiratory epithelial cells.

Capturing additional genetic risk from family history for improved polygenic risk prediction

The paper develops a latent factor model to capture additional genetic risk from family history, improving polygenic risk prediction for height and 11 complex diseases.

An Effector Index to Predict Causal Genes at GWAS Loci

The paper introduces the Effector Index, an algorithm to predict causal genes at GWAS loci using genomic features, achieving 85% AUC in type 2 diabetes validation.

Alternative splicing of OAS1 alters the risk for severe COVID-19

The paper identifies an alternative splicing variant of OAS1 that provides protection against severe COVID-19 in people of African ancestry, independent of Neanderthal haplotypes.

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity.

The paper develops a machine learning model to predict COVID-19 severity using exonic variants from whole exome sequencing data, finding that variants across all frequency categories contribute to severity.

Genome Wide Association Metanalysis Of Skull Bone Mineral Density Identifies Loci Relevant For Osteoporosis And Craniosynostosis

This study identifies 59 genome-wide significant loci for skull bone mineral density, including four novel loci, and links them to osteoporosis and craniofacial developmental defects.

Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality

This study examines how a major genetic risk factor for COVID-19 affects mortality and severity, finding stronger effects in younger adults.

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19

The paper investigates the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19 and finds no significant association.

Osteocyte Transcriptome Mapping Identifies a Molecular Landscape Controlling Skeletal Homeostasis and Susceptibility to Skeletal Disease

The paper maps the osteocyte transcriptome in mice, identifies 1239 genes, and links them to skeletal disease susceptibility in humans.

A Neanderthal OAS1 Isoform Protects Against COVID-19 Susceptibility and Severity: Results from Mendelian Randomization and Case-Control Studies

This study identifies OAS1 as a protective factor against COVID-19 severity and susceptibility using Mendelian randomization and case-control analyses.

The effect of smoking on multiple sclerosis: a mendelian randomization study

This study uses Mendelian randomization to assess if smoking causally affects multiple sclerosis risk, finding no significant association.

Genotype Imputation and Reference Panel: A Systematic Evaluation

The paper evaluates genotype imputation accuracy across Han Chinese and European populations using 394 reference panels, finding optimal diversity levels and highlighting the need for better Chinese reference panels.

Constrained Instruments and their Application to Mendelian Randomization with Pleiotropy

This paper introduces Constrained Instrumental Variable (CIV) methods to improve Mendelian randomization by handling pleiotropy, showing better performance in simulations and application to ADNI data.

An Atlas of Human and Murine Genetic Influences on Osteoporosis

This paper identifies 518 genetic loci associated with bone mineral density and fracture risk, validates causal genes in mice, and provides insights for osteoporosis drug development.

Machine Learning to Predict Osteoporotic Fracture Risk from Genotypes

This paper uses machine learning to predict osteoporotic fracture risk from genotypes, finding that genomic predictions outperform clinical risk factors in identifying fracture risk.