John Danesh

This study expands the human plasma proteome analysis using an enhanced SomaScan platform, identifying new genetic associations and disease mechanisms beyond the classical secretome.

The paper analyzes over 800,000 human genomes to assess penetrance of clinically relevant variants, finding that 95% of pLoF variants in severe diseases have explanations for lack of disease manifestation.

The paper shows that environmental variance increases with age, reducing heritability and PRS accuracy for multiple traits and diseases, suggesting younger cohorts are better for risk prediction models.

This paper introduces PHBC to estimate pleiotropic heritability across diseases, finding that about half of common disease heritability is shared with other diseases.

This study identifies metabolic reaction fluxes that interact with CAD risk alleles, revealing their role as amplifiers or buffers in disease susceptibility.

This study identifies genetic determinants of blood gene expression and splicing, linking them to molecular phenotypes and health outcomes through QTL analysis and colocalization.

This study evaluates the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm compared to current strategies.

The paper identifies misexpression of inactive genes in whole blood and links it to nearby rare structural variants using RNA and genome sequencing data.

Rare-variant depletion in 1kb windows of 76,156 gnomAD genomes, versus feature-adjusted mutation expectations, marks regulatory elements and outperforms seven alternative scores at flagging functional non-coding variants.

The paper develops a method to infer compound heterozygosity from exome sequencing data, achieving high accuracy in phasing rare variants for recessive disease diagnosis.

The paper identifies a NOTCH3 variant, p.Arg1231Cys, enriched in South Asians and strongly associated with stroke risk, highlighting the importance of genetic diversity in stroke research.

This study identifies 1,289 genetic signals for type 2 diabetes in 2.5 million individuals, revealing distinct clusters linked to vascular complications and highlighting ancestry-specific genetic risk factors.

The paper identifies pQTLs for 91 plasma proteins, finds novel associations, and uses MR to uncover causal roles in immune-mediated diseases, suggesting new therapeutic targets.

The paper develops genetic scores for 17,227 molecular traits using multi-omic data from INTERVAL and validates them across ancestries, demonstrating their utility in pathway analysis and disease association discovery.

The paper develops genetically personalised organ-specific metabolic models to identify associations between metabolic fluxes and disease risk, finding 97 fluxes linked to coronary artery disease.

This study identifies 400+ genetic loci associated with circulating metabolic traits and highlights pleiotropy and novel disease pathways.

The paper reports LTL measurements in 474,074 UK Biobank participants, identifying factors like age, sex, ethnicity, and white cell count associated with LTL variation.

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

The paper uses polygenic scores to identify plasma proteins causally linked to cardiometabolic diseases and finds some are targets for existing therapies.

This study uses Mendelian randomization to identify plasma proteins associated with stroke risk and potential therapeutic targets.

The paper identifies genetic associations between blood lipid metabolites and cardiometabolic disease loci in South Asian populations using lipidomics data from two studies.

This study identifies 592 genetic loci associated with 184 plasma proteins in 26,494 individuals and finds causal relationships between protein levels and disease.

A coronary artery disease GWAS of 181,522 cases among 1,165,690 participants yields 241 associations (54 new); an eight-predictor consensus nominates 185 candidate causal genes, 94 with ≥3 predictors.

PGS Catalog standardizes 192 curated polygenic scores and metadata (86 traits); reapplied in UK Biobank, eight of nine colorectal cancer scores predicted disease in European-ancestry participants.

ClinGen and the PGS Catalog expand the GRIPS guideline into a 22-item Polygenic Risk Score Reporting Statement covering study populations, model construction, evaluation, and clinical interpretation.

This study uses Mendelian randomization to examine if ACE inhibitors or cardiometabolic risk factors affect lung ACE2 and TMPRSS2 expression or plasma ACE2 levels, finding no overall association.

The paper characterizes the genetic structure of South Asian populations, identifies founder effects and high homozygosity, and develops a custom SNP array for genetic studies in the region.

This paper uses Mendelian randomization and colocalization to identify causal relationships between plasma proteins and disease phenotypes, finding 111 putatively causal effects.

This study identifies 5,552 blood-cell trait-variant associations across 746,667 individuals from 5 global populations, including 71 novel loci and ancestry-specific variants not found in European ancestry populations.

This study identifies 5,106 new genetic variants associated with blood cell traits using large-scale GWAS, highlighting the polygenic and monogenic basis of hematopoiesis.