Dirk S. Paul

Human genetics implicates a BACH2-NRF2 axis in fetal hemoglobin activation

This study identifies a BACH2-NRF2 axis regulating fetal hemoglobin activation through genetic and functional analyses in a large multi-ancestry cohort.

Atlas of glomerular disease-specific genetic effects on blood transcriptome

The paper generates disease-specific genetic effect maps on the blood transcriptome for five glomerular diseases using whole genome and transcriptome sequencing data from the CureGN cohort.

Integrating Natural and Engineered Genetic Variation to Decode Regulatory Influence on Blood Traits

The paper combines natural and engineered genetic variation to identify 22 non-coding variants affecting haematological traits and shows how a CUX1 variant impacts megakaryopoiesis.

Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus

The paper identifies USP18 as a negative regulator of interferon response at a lupus risk locus through trans-eQTL analysis in lymphoblastoid cell lines.

Large-scale genome-wide analyses with proteomics integration reveal novel loci and biological insights into frailty

This study identifies 1,242 novel genetic variants and 31 novel genes associated with frailty through genome-wide association and proteomics integration.

Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities

The paper identifies plasma proteomic markers linked to polygenic risk of type 2 diabetes and related comorbidities using proteogenomic data from biobanks and clinical trials.

Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes

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

Genome-wide meta-analysis conducted in three large biobanks expands the genetic landscape of lumbar disc herniations

This study conducts a genome-wide meta-analysis across three biobanks to identify new genetic loci associated with lumbar disc herniation, expanding the known genetic landscape.

Misexpression of inactive genes in whole blood is associated with nearby rare structural variants

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

Damaging mutations in LXRα uncouple lipogenesis from hepatotoxicity and implicate hepatic cholesterol sensing in human liver health

This study identifies damaging LXRα mutations linked to reduced triglycerides but increased liver enzyme levels and hepatotoxicity, suggesting LXR's role in liver health and cautioning against its inhibition for MASLD treatment.

Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation

This study investigates whether donor DNA methylation can predict acute graft-versus-host disease (aGVHD) in HCT, finding that a classifier developed from methylation data failed to validate in an independent cohort.

Strong protective effect of the APOL1 p.N264K variant against G2-associated FSGS and kidney disease

The paper shows the APOL1 p.N264K variant reduces the risk of FSGS and kidney disease in individuals with G2 APOL1 risk alleles.

Mapping pQTLs of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and novel therapeutic targets

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.

A FinnGen pilot clinical recall study for Alzheimer's disease

The paper demonstrates the feasibility of conducting clinical recall studies from the FinnGen biobank to collect customized clinical data from participants with Alzheimer's disease or mild cognitive disorder.

Assessing the role of rare pathogenic variants in heart failure progression by exome sequencing in 8,089 patients

This study identifies seven genes associated with heart failure progression using exome sequencing in 8,089 patients and prioritizes them for therapeutic target validation.

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

The paper identifies protein-truncating variants in BSN associated with severe adult-onset obesity, type 2 diabetes, and fatty liver disease, with no effect on childhood adiposity.

GWAS of preeclampsia and hypertensive disorders of pregnancy uncovers genes related to cardiometabolic, endothelial and placental function

This study conducts a GWAS of preeclampsia and hypertensive disorders of pregnancy, identifying 18 genome-wide significant loci, including novel associations with blood pressure and placental function.

An atlas of genetic scores to predict multi-omic traits

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.

Genetically personalised organ-specific metabolic models in health and disease

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.

Influences of rare protein-coding genetic variants on the human plasma proteome in 50,829 UK Biobank participants

The paper identifies rare protein-coding variants influencing plasma protein levels in 50,829 UK Biobank participants using exome-wide association studies.

Assessing the contribution of rare-to-common protein-coding variants to circulating metabolic biomarker levels via 412,394 UK Biobank exome sequences

The paper assesses the contribution of rare-to-common protein-coding variants to metabolic biomarker levels using UK Biobank exome sequences and identifies novel gene-biomarker relationships.

Human genetic evidence supports MAP3K15 inhibition as a therapeutic strategy for diabetes

The paper identifies MAP3K15 as a protective gene for diabetes through genetic analysis and shows its inhibition could be a therapeutic strategy.

Genome-wide analysis of blood lipid metabolites in over 5,000 South Asians reveals biological insights at cardiometabolic disease loci

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

Elucidating mechanisms of genetic cross-disease associations: an integrative approach implicates protein C as a causal pathway in arterial and venous diseases

The paper identifies a genetic variant in PROCR that influences protein C and factor VII levels, linking it to both reduced coronary artery disease risk and increased venous thromboembolism risk through opposing inflammatory and thrombotic mechanisms.

Interleukin-6 Receptor Signalling and Abdominal Aortic Aneurysm Growth Rates

The paper investigates the effect of the IL6R-Asp358Ala variant on AAA growth and evaluates IL-6 pathway blockade in mouse models, finding no significant growth rate reduction but improved survival with trans-signalling inhibition.

Genetic effects on promoter usage are highly context-specific and contribute to complex traits

The paper identifies context-specific genetic effects on promoter usage and shows they contribute to complex traits more than canonical splicing QTLs.

Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes

The paper identifies 61 novel mutations in the aged human testes, most affecting the RAS-MAPK pathway, showing evidence of selfish selection in the male germline.

Cell and tissue type independent age-associated DNA methylation changes are not rare but common

The paper analyzes DNA methylation changes across multiple tissues and cell types to show that a substantial portion of age-related methylation changes is shared between different cell/tissue types, with some sites showing age-related alterations in over 10 different types.

DNA methylation oscillation defines classes of enhancers

The paper identifies DNA methylation oscillations as a marker for enhancer classification, showing high predictive power compared to other methods.

ProGeM: A framework for the prioritisation of candidate causal genes at molecular quantitative trait loci

ProGeM prioritizes candidate causal genes at molecular QTLs by integrating biological and genome annotations, achieving high accuracy in identifying true positives.