Fibrotic diseases affect multiple organs and are associated with morbidity and mortality. To examine organ-specific and shared biologic mechanisms that underlie fibrosis in different organs, we developed machine learning models to quantify T1 time, a marker of interstitial fibrosis, in the liver, pancreas, heart and kidney among 43,881 UK Biobank participants who underwent magnetic resonance imaging. In phenome-wide association analyses, we demonstrate the association of increased organ-specific T1 time, reflecting increased interstitial fibrosis, with prevalent diseases across multiple organ systems. In genome-wide association analyses, we identified 27, 18, 11 and 10 independent genetic loci associated with liver, pancreas, myocardial and renal cortex T1 time, respectively. There was a modest genetic correlation between the examined organs. Several loci overlapped across the examined organs implicating genes involved in a myriad of biologic pathways including metal ion transport (SLC39A8, HFE and TMPRSS6), glucose metabolism (PCK2), blood group antigens (ABO and FUT2), immune function (BANK1 and PPP3CA), inflammation (NFKB1) and mitosis (CENPE). Finally, we found that an increasing number of organs with T1 time falling in the top quintile was associated with increased mortality in the population. Individuals with a high burden of fibrosis in ≥3 organs had a 3-fold increase in mortality compared to those with a low burden of fibrosis across all examined organs in multivariable-adjusted analysis (hazard ratio = 3.31, 95% confidence interval 1.77-6.19; P = 1.78 × 10). By leveraging machine learning to quantify T1 time across multiple organs at scale, we uncovered new organ-specific and shared biologic pathways underlying fibrosis that may provide therapeutic targets.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-024-03010-wDOI Listing

Publication Analysis

Top Keywords

organ-specific shared
12
examined organs
12
organs
8
multiple organs
8
shared biologic
8
machine learning
8
quantify time
8
interstitial fibrosis
8
liver pancreas
8
association analyses
8

Similar Publications

Diverse antibody repertoires spanning multiple lymphoid organs (i.e., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity.

View Article and Find Full Text PDF

Organ-level instance segmentation enables continuous time-space-spectrum analysis of pre-clinical abdominal photoacoustic tomography images.

Med Image Anal

December 2024

School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Medical Image Processing, Southern Medical University, Guangzhou 510515, China; Guangdong Province Engineering Laboratory for Medical Imaging and Diagnostic Technology, Southern Medical University, Guangzhou 510515, China. Electronic address:

Photoacoustic tomography (PAT), as a novel biomedical imaging technique, is able to capture temporal, spatial and spectral tomographic information from organisms. Organ-level multi-parametric analysis of continuous PAT images are of interest since it enables the quantification of organ specific morphological and functional parameters in small animals. Accurate organ delineation is imperative for organ-level image analysis, yet the low contrast and blurred organ boundaries in PAT images pose challenge for their precise segmentation.

View Article and Find Full Text PDF

Molecular background of the diverse metabolic profiles in leaves and inflorescences of naked catmint ( L.).

Front Plant Sci

November 2024

Department of Plant Physiology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.

L. shares a typical secondary chemistry with other species (fam. ), characterized by the tendency to intensively produce monoterpenoid iridoids, whereas the phenylpropanoid chemistry is steered towards the production of a caffeic acid ester, rosmarinic acid.

View Article and Find Full Text PDF

Introduction: Multilocus Inherited Neoplasia Allele Syndrome (MINAS) is a condition defined by the presence of germline pathogenic variants in more than one Cancer Susceptibility Gene (CSG). MINAS is still underreported in the literature and public databases. Since MINAS-related phenotypes are difficult to predict, case descriptions may contribute to risk assessment, treatment, and personalized surveillance for proband and relatives.

View Article and Find Full Text PDF

Fibrosis, an excessive self-repair response, is an age-related pathological process that universally affects various major organs such as the heart, liver, kidney, and lungs. Continuous accumulation of pathological tissue fibrosis destroys structural integrity and causes loss of function, with consequent organ failure and increased mortality. Although some differences exist in the triggering mechanisms and pathophysiologic manifestations of organ-specific fibrosis, they usually share similar cascading responses and features, including chronic inflammatory stimulation, parenchymal cell injury, and macrophage recruitment.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!