Broadcasters, receivers, functional groups of metabolites, and the link to heart failure by revealing metabolomic network connectivity
Artikel i vetenskaplig tidskrift, 2024

Background and Objective: Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline.
Methods: We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites.
Results: We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet.
Conclusion: Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF.

Genetic variation

Heart failure

Metabolomics

Structural equation modeling

Causal networks

Confounding metabolites

Data-driven or Bayesian networks

Författare

Azam Yazdani

Broad Institute

Harvard Medical School

Raul Mendez-Giraldez

Beckman Coulter

Akram Yazdani

University of Texas Medical School

Rui Sheng Wang

Harvard Medical School

Daniel J. Schaid

Mayo Clinic

Sek Won Kong

Children's Hospital Boston

M. Reza Hadi

Iran University of Science and Technology

Ahmad Samiei

Children's Hospital Boston

Esmat Samiei

Gamelectronic

Clemens Wittenbecher

Chalmers, Life sciences, Livsmedelsvetenskap

Jessica Lasky-Su

Harvard Medical School

Clary B. Clish

Broad Institute

Jochen D. Muehlschlegel

Harvard Medical School

Francesco Marotta

ReGenera R & amp;D International for Aging Intervention and Vitality & amp; Longevity Medical Science Commission

Joseph Loscalzo

Harvard Medical School

Samia Mora

Harvard Medical School

Daniel I. Chasman

Harvard Medical School

Martin G. Larson

Boston University

Sarah H. Elsea

Baylor College of Medicine

Metabolomics

1573-3882 (ISSN) 1573-3890 (eISSN)

Vol. 20 4 71

Ämneskategorier

Kardiologi

Näringslära

DOI

10.1007/s11306-024-02141-y

Mer information

Senast uppdaterat

2024-08-07