Biomedical subjects

Torben Hansen

Publications and source records attributed to Torben Hansen.

3 recordsLinked to original sources

PubMed2026

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

Humans↗

PubMed2026

Colocalization and functional analyses identify GBE1 as a gene linking muscle strength and cardiometabolic fitness.

Handgrip strength is a proxy for muscular fitness, an indicator for general health status, and is associated with cardiometabolic health. The mechanisms connecting handgrip strength to skeletal muscle function are incompletely understood. We applied integrated linkage-disequilibrium-adjusted colocalization analysis of genome-wide association study summary statistics for handgrip strength, combined with expression and splicing quantitative trait loci from skeletal muscle, and identified glycogen branching enzyme 1 (GBE1) as a candidate gene for handgrip strength. CRISPR-interference knockdown of GBE1 in immortalized human skeletal muscle cells (HMCL-7304) demonstrated decreased glycogen content and accumulation of polyglucosan bodies. Knockdown of GBE1 led to increased oxygen consumption rate, oxidative stress, and changes in mitochondrial morphology. Transcriptomic profiling of GBE1 knockdown cells identified upregulation of the human superoxide dismutase 2 and enrichment of pathways related to muscle contraction and oxidative stress responses. These functional genomic analyses prioritize GBE1 as a muscle-relevant candidate gene for handgrip strength and provide mechanistic insights to muscle fitness.NEW & NOTEWORTHY Colocalization of genome-wide association study (GWAS) loci with quantitative trait loci (QTL) in skeletal muscle tissue identified GBE1 as a candidate for handgrip strength. Cellular phenotypes with GBE1 knockdown in immortalized human skeletal muscle cells include decreased glycogen content, accumulation of polyglucosan bodies, changes in mitochondrial function and morphology, and increased expression of reactive oxygen species (ROS) scavengers. Transcriptomic changes suggest a role for GBE1 in muscle contraction and oxidative stress-mediated responses.

Humans↗

PubMed2025

Scalable Deep Learning of Histology Images Reveals Genetic and Phenotypic Determinants of Adipocyte Hypertrophy.

BACKGROUND: White adipose tissue dysfunction has emerged as a critical factor in cardiometabolic disease development, yet the cellular microstructure and genetic architecture of adipocyte morphology remain poorly explored. METHODS: We introduce Adipocyte U-Net 2.0, an advanced deep learning method for the semantic segmentation of adipose tissue histology, enabling analysis of over 27 million adipocytes from 2,667 individuals. FINDINGS: Our approach revealed that adipocyte hypertrophy associates with metabolic dysfunction, including increased fasting glucose, glycated hemoglobin, leptin, and triglycerides, with decreased adiponectin and HDL cholesterol levels. Through the largest genome-wide association study of adipocyte size to date (NSubcutaneous = 2,066, NVisceral = 1,878), we identified four genome-wide significant loci: two in sex-combined analysis (rs73184721 in NAALADL2 and rs200047724 in NRXN3) and two female-specific variants (rs140503338 and rs11656704 in ULK2). Notably, these genetic associations showed congruent relationships with cardiometabolic traits, suggesting shared biological mechanisms. INTERPRETATION: Our findings demonstrate the utility of deep learning for adipocyte phenotyping at scale and provide novel insights into the genetic basis of adipocyte morphology and its relationship to metabolic disease.

Journal Article↗