Markku Laakso

Genetic integration with cell-specific nucleosome positioning resolves causal relationships underlying chromatin accessibility profiles

The paper maps cell type-specific genetic effects on nucleosome-free regions and nucleosome occupancy using snATAC-seq data from human muscle biopsies, showing causal relationships between these elements and GWAS traits.

Erosion of regenerative regulation: age-associated shifts in the skeletal muscle fiber epigenome and transcriptome

The paper identifies age-associated changes in the skeletal muscle epigenome and transcriptome, revealing shifts in chromatin accessibility and gene expression linked to metabolic and senescence pathways.

Integrated Analysis of Skeletal Muscle Transcriptional Networks Characterizes Dysregulation in Pathways and Trait-Associated Regulatory Regions in Type 2 Diabetes

The paper identifies dysregulated pathways and candidate driver genes in skeletal muscle from individuals with type 2 diabetes using co-expression networks and single-nucleus RNA-seq data.

MetaboXcan: A multiomic framework linking genetically predicted metabolites, gene expression, and complex traits

MetaboXcan predicts plasma metabolites from genetic data and associates them with complex traits, identifying disease risk genes and metabolites in chronic kidney disease.

Donor-matched iPSC model reveals context-dependent T2D genetic signals in fibro-adipogenic progenitors

The paper uses donor-matched iPSC-derived FAPs to show that T2D GWAS signals are enriched in adipogenic FAP subtypes under high-insulin exposure.

Genealogy based trait association with LOCATER boosts power at loci with allelic heterogeneity

The paper introduces LOCATER, a genealogy-based method that improves trait association power by leveraging haplotype diversity and allelic heterogeneity, identifying novel associations and recovering known loci in a Finnish cohort.

Inverse directions of association of higher physical activity and higher insulin resistance with human skeletal muscle cell type abundance and fiber type-level gene expression

The paper examines how physical activity and insulin resistance relate to skeletal muscle cell type abundance and gene expression in humans, finding inverse associations with specific cell types and gene expression patterns.

Single-cell DNA methylome and 3D genome atlas of the human subcutaneous adipose tissue

The paper characterizes the epigenomic and 3D genomic landscape of human subcutaneous adipose tissue at the cell-type level and links epigenomic variation to abdominal obesity risk.

Longitudinal adipose tissue single cell transcriptomics reveals genes and variants regulating weight loss after bariatric surgery

This study uses longitudinal single-cell adipose transcriptomics to identify genes and variants associated with weight loss after bariatric surgery and shows that BMI polygenic risk scores predict weight loss outcomes.

Probabilistic Fine-mapping of Putative Causal Genes

This paper introduces INTERFACE, a probabilistic fine-mapping method that improves the identification of causal genes by integrating colocalization and transcriptome-wide association evidence.

Human iPSC-derived pericyte-like cells carrying APP Swedish mutation overproduce beta-amyloid and induce cerebral amyloid angiopathy-like changes

This study shows that human iPSC-derived pericyte-like cells with the APP Swedish mutation overproduce beta-amyloid and exhibit CAA-like features in vitro.

Integrative analysis of the genome, transcriptome, and proteome identifies causal mechanisms of complex traits.

The paper introduces Multi-INTACT, a method that integrates transcriptome-wide association studies with protein QTL data to identify causal genes for metabolites, finding that both gene products are relevant for most gene nominations.

Population-scale skeletal muscle single-nucleus multi-omic profiling reveals extensive context specific genetic regulation

The paper performs population-scale single-nucleus multi-omic profiling of skeletal muscle to identify genetic regulation across cell types and traits.

Adipose tissue eQTL meta-analysis reveals the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits

The paper identifies additional eQTL signals in adipose tissue and shows they contribute to cardiometabolic traits through gene dosage effects.

A multi-ancestry genome-wide meta-analysis, fine-mapping, and target gene prioritization to characterize the genetic architecture of adiponectin.

This study performs a multi-ancestry GWAS for adiponectin, identifies 22 loci, and prioritizes target genes using GPScore, revealing novel genes and pathways involved in metabolic regulation.

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.

DrFARM: Identification and inference for pleiotropic gene in GWAS

DrFARM identifies pleiotropic gene variants by jointly analyzing genetic data and controlling false discovery rate, finding 288 new metabolite associations in a metabolic study.

Genome-wide characterization of circulating metabolic biomarkers reveals substantial pleiotropy and novel disease pathways

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

SARS-CoV-2 infection of human neurons requires endosomal cell entry and can be blocked by inhibitors of host phosphoinositol-5 kinase

This study shows that SARS-CoV-2 can infect a small fraction of human cortical neurons via the endosomal pathway, and this infection can be blocked by apilimod.

ACE2 expression in adipose tissue is associated with COVID-19 cardio-metabolic risk factors and cell type composition

The paper examines the association between adipose tissue ACE2 expression and cardio-metabolic risk factors, finding lower ACE2 levels linked to T2D, obesity, and inflammation-related cell type changes.

Genome-wide association study of 1,391 plasma metabolites in 6,136 Finnish men identifies 303 novel signals and provides biological insights into human diseases

This study identifies 303 novel genetic signals associated with plasma metabolites in Finnish men, revealing biological insights into disease mechanisms.

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.

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.

Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences

Association of Structural Variation with Cardiometabolic Traits in Finns

This study identifies 31 genome-wide significant associations between structural variations and cardiometabolic traits in Finns, including two novel loci with strong phenotypic effects.

Large-scale association analyses identify host factors influencing human gut microbiome composition

The paper identifies 31 host genetic loci influencing gut microbiome composition through GWAS and suggests causal effects in inflammatory diseases.

Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study

This study develops machine learning models to predict liver fat content using multi-omic and clinical data from NAFLD patients, achieving higher accuracy than existing tools.

A comprehensive study of metabolite genetics reveals strong pleiotropy and heterogeneity across time and context

This study identifies 588 SNP-metabolite associations using the METSIM cohort, revealing pleiotropy, temporal changes, and age-related genetic control shifts.

Exome sequencing identifies high impact trait-associated alleles enriched in Finns

Exome sequencing in Finnish populations identifies rare trait-associated alleles with higher frequencies and geographical clustering, revealing 30 novel associations with quantitative traits.

Reverse GWAS: Using Genetics to Identify and Model Phenotypic Subtypes

This paper introduces Reverse GWAS (RGWAS) to identify and validate phenotypic subtypes using genetics, finding three novel metabolic subtypes and showing differential treatment effects.