Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(1), P. 44 - 53

Published: Jan. 1, 2023

Language: Английский

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Atlas of plasma NMR biomarkers for health and disease in 118,461 individuals from the UK Biobank

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 3, 2023

Abstract Blood lipids and metabolites are markers of current health future disease risk. Here, we describe plasma nuclear magnetic resonance (NMR) biomarker data for 118,461 participants in the UK Biobank. The biomarkers cover 249 measures lipoprotein lipids, fatty acids, small molecules such as amino ketones, glycolysis metabolites. We provide an atlas associations these to prevalence, incidence, mortality over 700 common diseases ( nightingalehealth.com/atlas ). results reveal a plethora associations, including susceptibility infectious risk various cancers, joint disorders, mental outcomes, indicating that abundant circulating beyond cardiometabolic diseases. Clustering analyses indicate similar association patterns across different types, suggesting latent systemic connectivity diverse set This work highlights value NMR based metabolic profiling large biobanks public research translation.

Language: Английский

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Metabolomic profiles predict individual multidisease outcomes

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2309 - 2320

Published: Sept. 22, 2022

Abstract Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored potential nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors onset 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal neurological diseases cancers. Specifically, trained a neural network learn disease-specific states from 168 circulating metabolic markers measured in 117,981 participants with ~1.4 million person-years follow-up UK Biobank validated model four independent cohorts. We found be associated incident event rates all investigated except breast cancer. For 10-year outcome prediction 15 endpoints, without established contribution, combination age sex state equaled or outperformed predictors. Moreover, added predictive information over comprehensive variables eight diseases, type 2 diabetes, dementia heart failure. Decision curve analyses showed that improvements translated into utility wide range decision thresholds. Taken together, our study demonstrates both limitations NMR-derived as assay many simultaneously.

Language: Английский

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Taurine deficiency as a driver of aging

Science, Journal Year: 2023, Volume and Issue: 380(6649)

Published: June 8, 2023

Aging is associated with changes in circulating levels of various molecules, some which remain undefined. We find that concentrations taurine decline aging mice, monkeys, and humans. A reversal this through supplementation increased the health span (the period healthy living) life mice monkeys. Mechanistically, reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, attenuated inflammaging. In humans, lower correlated several age-related diseases after acute endurance exercise. Thus, deficiency may be a driver because its increases worms, rodents, primates worms rodents. Clinical trials humans seem warranted to test whether might drive

Language: Английский

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OmicsNet 2.0: a web-based platform for multi-omics integration and network visual analytics

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(W1), P. W527 - W533

Published: May 5, 2022

Abstract Researchers are increasingly seeking to interpret molecular data within a multi-omics context gain more comprehensive picture of their study system. OmicsNet (www.omicsnet.ca) is web-based tool developed allow users easily build, visualize, and analyze networks rich relationships among lists ‘omics features interest. Three major improvements have been introduced in 2.0, which include: (i) enhanced network visual analytics with eleven 2D graph layout options novel 3D module layout; (ii) support for three new types: single nucleotide polymorphism (SNP) list from genetic variation studies; taxon microbiome profiling studies, as well liquid chromatography–mass spectrometry (LC–MS) peaks untargeted metabolomics; (iii) measures improve research reproducibility by coupling R command history the release companion OmicsNetR package, generation persistent links share interactive views. We performed case using obtained recent large-scale investigation on inflammatory bowel disease (IBD) demonstrated that was able quickly create meaningful facilitate hypothesis mechanistic insights.

Language: Английский

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The metabolomics of human aging: Advances, challenges, and opportunities

Science Advances, Journal Year: 2022, Volume and Issue: 8(42)

Published: Oct. 19, 2022

As the global population becomes older, understanding impact of aging on health and disease paramount. Recent advancements in multiomic technology have allowed for high-throughput molecular characterization at level. Metabolomics studies that analyze small molecules body can provide biological information across a diversity processes. Here, we review growing population-scale metabolomics research humans, identifying major trends field, implicated pathways, how these pathways relate to aging. We conclude by assessing main challenges date, opportunities advancing outlook precision applications.

Language: Английский

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Rare and common genetic determinants of metabolic individuality and their effects on human health

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(11), P. 2321 - 2332

Published: Nov. 1, 2022

Abstract Garrod’s concept of ‘chemical individuality’ has contributed to comprehension the molecular origins human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot metabolism at scale. We studied genetic architecture plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant–metabolite associations ( P < 1.25 × 10 −11 ) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% associations. Jointly modeling each region, we 423 regional, co-regulated, clusters called genetically influenced metabotypes. assigned causal genes for 62.4% these metabotypes, providing new insights into fundamental metabolite physiology clinical relevance, including metabolite-guided discovery potential adverse drug effects DPYD SRD5A2 ). show strong enrichment inborn errors metabolism-causing genes, examples phenotypes non-pathogenic variant carriers matching characteristics metabolism. Systematic, phenotypic follow-up metabolite-specific scores revealed multiple etiological relationships.

Language: Английский

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Plasma proteomic profiles predict individual future health risk

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 28, 2023

Developing a single-domain assay to identify individuals at high risk of future events is priority for multi-disease and mortality prevention. By training neural network, we developed disease/mortality-specific proteomic score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative markedly stratified the 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, genitourinary diseases, cancers, mortality. The discriminations witnessed accuracies achieved by ProRS 10 endpoints (e.g., cancer, dementia, death), with C-indexes exceeding 0.80. Notably, produced much better or equivalent predictive performance than established clinical indicators almost all endpoints. Incorporating predictors enhanced power most endpoints, but this combination only exhibited limited improvement when compared alone. Some proteins, e.g., GDF15, important discriminative values various diseases. We also showed that good observed could be largely translated into practical utility. Taken together, profiles may serve as replacement complex laboratory tests measures refine comprehensive assessments multiple diseases mortalities simultaneously. Our models were internally validated Biobank; thus, further independent external validations are necessary confirm our findings before application settings.

Language: Английский

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Biological and functional multimorbidity—from mechanisms to management

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(7), P. 1649 - 1657

Published: July 1, 2023

Language: Английский

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Assessment of six surrogate insulin resistance indexes for predicting cardiometabolic multimorbidity incidence in Chinese middle‐aged and older populations: Insights from the China health and retirement longitudinal study

Diabetes/Metabolism Research and Reviews, Journal Year: 2024, Volume and Issue: 40(1)

Published: Jan. 1, 2024

Insulin resistance (IR) is associated with cardiometabolic multimorbidity (CMM). We aimed to explore the predictive value of six surrogate IR indexes-Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), triglyceride-glucose (TyG), atherogenic plasma (AIP), TyG-body mass (TyGBMI), and TyG-waist circumference (TyGwaist)-to establish CMM incidence in Chinese middle-aged older populations.

Language: Английский

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