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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts

Ghosh, Nilanjana ; Lejonberg, Carl LU ; Czuba, Tomasz LU ; Dekkers, Koen ; Robinson, Richard ; Ärnlöv, Johan ; Melander, Olle LU orcid ; Smith, Maya Landenhed ; Evans, Anne M. and Gidlöf, Olof LU , et al. (2024) In Scientific Reports 14(1).
Abstract

Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The... (More)

Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
14
issue
1
article number
8933
publisher
Nature Publishing Group
external identifiers
  • scopus:85190669187
  • pmid:38637659
ISSN
2045-2322
DOI
10.1038/s41598-024-59388-7
language
English
LU publication?
yes
id
a5c35b85-032f-4cae-becb-8141948442a5
date added to LUP
2024-04-29 10:13:49
date last changed
2024-05-13 11:32:01
@article{a5c35b85-032f-4cae-becb-8141948442a5,
  abstract     = {{<p>Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50–80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.</p>}},
  author       = {{Ghosh, Nilanjana and Lejonberg, Carl and Czuba, Tomasz and Dekkers, Koen and Robinson, Richard and Ärnlöv, Johan and Melander, Olle and Smith, Maya Landenhed and Evans, Anne M. and Gidlöf, Olof and Gerszten, Robert E. and Lind, Lars and Engström, Gunnar and Fall, Tove and Smith, J. Gustav}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-59388-7}},
  doi          = {{10.1038/s41598-024-59388-7}},
  volume       = {{14}},
  year         = {{2024}},
}