ArticleCell metabolism2023
Protein-metabolite association studies identify novel proteomic determinants of metabolite levels in human plasma.
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Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18citing papers in PubMed
8.3field-weighted citation impact, top 2% of its field
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Who cites it
18 citing papers in PubMed, 54 citations in OpenAlex.
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- Distinct demethylation pathways of rice- and fish-derived methylmercury in pregnant women revealed by compound-specific isotope analysis.Eco-Environment & Health · 2026Article
- HUBMet: an integrative database and analytical platform for human blood metabolites and metabolite-protein associations.Genome biology · 2025Article
- Genetic architecture and analysis practices of circulating metabolites in the NHLBI Trans-Omics for Precision Medicine Program.American journal of human genetics · 2025Article
- Metabolomic Analysis of Cauda Epididymal Fluid in Yaks and Cattle.Animals : an open access journal from MDPI · 2025Article
- Longitudinal analysis of genetic and environmental interplay in human metabolic profiles and the implication for metabolic health.Genome medicine · 2025Article
- Trans-right ventricle metabolite gradients in obesity highlight multiple metabolic pathways.Physiological reports · 2025Article
- Macrophage SUCLA2 coupled glutaminolysis manipulates obesity through AMPK.Nature communications · 2025Article
- Microbiota contribute to regulation of the gut-testis axis in seasonal spermatogenesis.The ISME journal · 2025Article
- Cerebrospinal Fluid Metabolomics and Proteomics Integration in Neurological Syndromes.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Transcriptome and metabolome analysis of the responses of salt resistance of differentFrontiers in plant science · 2025Article
- Multi-omics approach to dissect the significance of lipid metabolism in helper T cell subset.Frontiers in immunology · 2025Review
- A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes.Nature communications · 2024Article
- Integrated proteomic and metabolomic profiling reveals novel insights on the inflammation and immune response in HFpEF.BMC genomics · 2024Article
- Multiomics Picture of Obesity in Young Adults.Biology · 2024Article
- Genetics unravels protein-metabolite relationships.Trends in endocrinology and metabolism: TEM · 2024Article
Corrections and comments
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Authors and funding
41 authors at 14 institutions in 1 country.
Mark D BensonDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Aaron S EismanDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Center for Biomedical Informatics, Brown University, Providence, RI, USA.
Usman A TahirDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Daniel H KatzDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Shuliang DengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Debby NgoDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Jeremy M RobbinsDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Alissa HofmannDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Xu ShiDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Shuning ZhengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Michelle KeyesDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Zhi YuBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Yan GaoUniversity of Mississippi Medical Center, Jackson, MS, USA.
Laurie FarrellDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Dongxiao ShenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Zsu-Zsu ChenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Daniel E CruzDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Mario SimsUniversity of Mississippi Medical Center, Jackson, MS, USA.
Adolfo CorreaUniversity of Mississippi Medical Center, Jackson, MS, USA.
Russell P TracyDepartment of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Peter DurdaDepartment of Pathology Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Yongmei LiuDepartment of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
W Craig JohnsonDepartment of Biostatistics, University of Washington, Seattle, WA, USA.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Jie YaoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Yii-Der Ida ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Ani W ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA; Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Deepti JainUniversity of Washington, Seattle, WA, USA.
Qiong YangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Claude BouchardHuman Genomic Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Mark A SarzynskiDepartment of Exercise Science, University of South Carolina, Columbia, Columbia, SC, USA.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Thomas J WangDepartment of Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
James G WilsonDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Clary B ClishBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Indra Neil SarkarCenter for Biomedical Informatics, Brown University, Providence, RI, USA.
Pradeep NatarajanBroad Institute of Harvard and MIT, Cambridge, MA, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine Harvard Medical School, Boston, MA, USA.
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA. Electronic address: rgerszte@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USUCLA Medical Center · USBroad Institute · USJackson Memorial Hospital · USUniversity of Vermont · USUniversity of Washington · USBoston University · USBrown University · USDuke Medical Center · USPennington Biomedical Research Center · USSouthwestern Medical Center · USUniversity of South Carolina · USUniversity of Virginia · USUniversity of Virginia Health System · US
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MUCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MA Biochemical Roadmap of Exercise Signaling - Pilot Project for MoTrPAC ConsortiumU24DK112340 · NIDDK · BROAD INSTITUTE, INC. · PI STEVEN A CARR, Clary B Clish · 2017 to 2026
$16.2MStudies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5MMetabolomic predictors of insulin resistance and diabetesR01DK081572 · NIDDK · VANDERBILT UNIVERSITY · PI CLISH, CLARY B, GERSZTEN, ROBERT E · 2008 to 2025
$9.3MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MHERITAGE STUDY: GENETICS, EXERCISE &RISK FACTORSR01HL045670 · NHLBI · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI RANKINEN, TUOMO · 1992 to 2010
$6.8MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NHGRI NIH HHS K99 HG012956NHGRI NIH HHS U54 HG003067NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201000001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011CNHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012CNHLBI NIH HHS HHSN268201800012INHLBI NIH HHS HHSN268201800014CNHLBI NIH HHS HHSN268201800014INHLBI NIH HHS HHSN268201800015INHLBI NIH HHS K08 HL145095NHLBI NIH HHS K08 HL161445NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL045670NHLBI NIH HHS R01 HL047317NHLBI NIH HHS R01 HL047323NHLBI NIH HHS R01 HL047327NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL133870NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL146462NHLBI NIH HHS U01 HL120393NIDDK NIH HHS K23 DK127073NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK081572NIDDK NIH HHS U24 DK112340NIGMS NIH HHS P30 GM118430NIMHD NIH HHS HHSN268201800013ININR NIH HHS R01 NR019628NLM NIH HHS F30 LM013320
Abstract
Although many novel gene-metabolite and gene-protein associations have been identified using high-throughput biochemical profiling, systematic studies that leverage human genetics to illuminate causal relationships between circulating proteins and metabolites are lacking. Here, we performed protein-metabolite association studies in 3,626 plasma samples from three human cohorts. We detected 171,800 significant protein-metabolite pairwise correlations between 1,265 proteins and 365 metabolites, including established relationships in metabolic and signaling pathways such as the protein thyroxine-binding globulin and the metabolite thyroxine, as well as thousands of new findings. In Mendelian randomization (MR) analyses, we identified putative causal protein-to-metabolite associations. We experimentally validated top MR associations in proof-of-concept plasma metabolomics studies in three murine knockout strains of key protein regulators. These analyses identified previously unrecognized associations between bioactive proteins and metabolites in human plasma. We provide publicly available data to be leveraged for studies in human metabolism and disease.
Indexed as
MetabolomicsProteomicsAnimalsGenome-Wide Association StudyHumansMicePolymorphism, Single NucleotideSignal Transductionfunctional genomicsgenome-wide association studygenomicsGWASmetabolomicsmulti-omicspathway discoveryproteomics
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.