Leif Groop

Inferring compound heterozygosity from large-scale exome sequencing data

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

Genetic analysis of blood molecular phenotypes reveals regulatory networks affecting complex traits: a DIRECT study.

The paper identifies shared genetic regulation across mRNA, proteins, and metabolites in blood, revealing networks and mediators of GWAS variants.

Pharmacogenomics of GLP-1 Receptor Agonists: A genome-wide analysis of observational data and large randomized controlled trials

This study identifies genetic variants associated with glycaemic response to GLP-1 receptor agonists using observational and trial data, finding variants in GLP-1R and ARRB1 linked to HbA1c reduction.

The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α

This study shows that TYK2 is critical for β-cell development by regulating KRAS and IFN responses, suggesting TYK2 inhibition as a therapeutic target for type 1 diabetes.

Genetic regulation of RNA splicing in human pancreatic islets

The paper identifies splicing QTLs in human pancreatic islets that contribute to type 2 diabetes susceptibility by affecting gene splicing and revealing novel molecular mechanisms.

Islet Gene View - a tool to facilitate islet research

The paper introduces Islet Gene View (IGW), a platform that integrates gene expression and phenotypic data from pancreatic islets to explore T2D-related gene expression changes and their functional implications.

Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease

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.

TIGER: The gene expression regulatory variation landscape of human pancreatic islets

The paper creates TIGER, a resource integrating RNA-seq and genotyping data from human pancreatic islets to identify eQTLs and their associations with type 2 diabetes.

Cohort Profile: Epigenetics in Pregnancy (EPIPREG)-population-based sample of European and South Asian pregnant women living in Norway with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes

EPIPREG collects DNA methylation data from pregnant women in Norway to study associations with cardiometabolic traits and ethnic disparities in health.

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

The paper evaluates penetrance and variable expressivity of monogenic metabolic conditions using exome data from 77,184 individuals, finding that monogenic variants have larger effect sizes than polygenic scores but low penetrance.

Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification

This study performs a GWAS on random glucose measurements in 493,036 individuals, identifying 128 loci associated with glycaemic traits and providing insights into diabetes biology and treatment.

Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health

This study identifies five genetic loci associated with obstructive sleep apnoea and finds a causal link between BMI and OSA through polygenic risk scores and Mendelian randomization.

Influence of genetic variants on gene expression in human pancreatic islets - implications for type 2 diabetes

The paper investigates how genetic variants affect gene expression in human pancreatic islets and identifies candidate genes linked to type 2 diabetes.

Evaluating potential drug targets through human loss-of-function genetic variation

The paper evaluates potential drug targets using loss-of-function genetic variants from gnomAD, highlighting the importance of deep curation and targeted recall studies for drug discovery.

The mutational constraint spectrum quantified from variation in 141,456 humans

From 125,748 exomes and 15,708 genomes, 443,769 high-confidence predicted loss-of-function variants yield LOEUF, a continuous gene intolerance score tracking mouse lethality, cell essentiality, and disease associations.

Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinsons disease

The paper analyzes loss-of-function variants in LRRK2 across large genomic datasets to assess the safety of partial LRRK2 inhibition as a Parkinson's disease therapy.

Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes

The paper analyzes multi-nucleotide variants (MNVs) in 125,748 exomes and 15,708 genomes, identifying their distribution, mutational origins, and functional implications.

Loss of ZnT8 function protects against diabetes by enhanced insulin secretion

The paper shows that a loss-of-function variant in ZnT8 improves insulin secretion and protects against type 2 diabetes by enhancing glucose responsiveness and proinsulin conversion.

Human pancreatic islet 3D chromatin architecture provides insights into the genetics of type 2 diabetes

The paper links diabetes-associated enhancers with their target genes using 3D chromatin architecture in human pancreatic islets, revealing genetic variants that impact insulin secretion heritability.

Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen

This study identifies 16 genome-wide significant loci associated with diabetic kidney disease, including a protective variant in the COL4A3 gene.

Exome-wide association study on Albuminuria identifies a novel rare variant in CUBN and additional genes, in 33,985 Europeans with and without diabetes

Turning vice into virtue: Using Batch-Effects to Detect Errors in Large Genomic Datasets

The paper detects systematic errors in large genomic datasets by analyzing batch effects, finding coding regions have more errors than non-coding regions.

Genetic discovery and translational decision support from exome sequencing of 20,791 type 2 diabetes cases and 24,440 controls from five ancestries

This study identifies rare genetic variants associated with type 2 diabetes using exome sequencing of 20,791 cases and 24,440 controls, and provides a Bayesian framework to improve variant prioritization.

Controllability in an islet specific regulatory network identifies the transcriptional factor NFATC4, which regulates Type 2 Diabetes associated genes

The paper identifies NFATC4 as a key regulator of Type 2 Diabetes genes by analyzing a gene regulatory network in pancreatic islets and linking it to eQTLs and differential expression.

Haplotype sharing provides insights into fine-scale population history and disease in Finland

This study uses haplotype sharing among Finns to reconstruct recent population history and identify regions with increased rare disease variant sharing.

Narrow-sense heritability estimation of complex traits using identity-by-descent information.

This paper estimates narrow-sense heritability using identity-by-descent information in unrelated individuals and finds that IBD-based methods can capture rare variant contributions but are affected by stratification.

Fine-mapping of an expanded set of type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

This study fine-maps type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps, identifying 73 variants with >80% posterior probability of association.

Heterozygous RFX6 protein truncating variants cause Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance

This study identifies heterozygous RFX6 protein truncating variants as a cause of MODY with reduced penetrance, using genetic analysis and cohort comparisons.

Human pancreatic β cell lncRNAs control cell-specific regulatory networks

This study identifies β cell-specific lncRNAs that regulate transcriptional networks and show dysregulation in type 2 diabetes.