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Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans

Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method...

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Autores principales: Chen, Zsu-Zsu, Pacheco, Julian Avila, Gao, Yan, Deng, Shuliang, Peterson, Bennet, Shi, Xu, Zheng, Shuning, Tahir, Usman A., Katz, Daniel H., Cruz, Daniel E., Ngo, Debby, Benson, Mark D., Robbins, Jeremy M., Guo, Xiuqing, del Rocio Sevilla Gonzalez, Magdalena, Manning, Alisa, Correa, Adolfo, Meigs, James B., Taylor, Kent D., Rich, Stephen S., Goodarzi, Mark O., Rotter, Jerome I., Wilson, James G., Clish, Clary B., Gerszten, Robert E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630088/
https://www.ncbi.nlm.nih.gov/pubmed/35998269
http://dx.doi.org/10.2337/db22-0033
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author Chen, Zsu-Zsu
Pacheco, Julian Avila
Gao, Yan
Deng, Shuliang
Peterson, Bennet
Shi, Xu
Zheng, Shuning
Tahir, Usman A.
Katz, Daniel H.
Cruz, Daniel E.
Ngo, Debby
Benson, Mark D.
Robbins, Jeremy M.
Guo, Xiuqing
del Rocio Sevilla Gonzalez, Magdalena
Manning, Alisa
Correa, Adolfo
Meigs, James B.
Taylor, Kent D.
Rich, Stephen S.
Goodarzi, Mark O.
Rotter, Jerome I.
Wilson, James G.
Clish, Clary B.
Gerszten, Robert E.
author_facet Chen, Zsu-Zsu
Pacheco, Julian Avila
Gao, Yan
Deng, Shuliang
Peterson, Bennet
Shi, Xu
Zheng, Shuning
Tahir, Usman A.
Katz, Daniel H.
Cruz, Daniel E.
Ngo, Debby
Benson, Mark D.
Robbins, Jeremy M.
Guo, Xiuqing
del Rocio Sevilla Gonzalez, Magdalena
Manning, Alisa
Correa, Adolfo
Meigs, James B.
Taylor, Kent D.
Rich, Stephen S.
Goodarzi, Mark O.
Rotter, Jerome I.
Wilson, James G.
Clish, Clary B.
Gerszten, Robert E.
author_sort Chen, Zsu-Zsu
collection PubMed
description Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method that measures 305 targeted or “known” and 2,342 nontargeted or “unknown” compounds in fasting plasma samples from 2,750 participants (315 incident cases) in the Jackson Heart Study (JHS)—a community cohort of self-identified African Americans—who are underrepresented in omics studies. We found 307 unique compounds (82 known) associated with diabetes after adjusting for age and sex at a false discovery rate of <0.05 and 124 compounds (35 known, including 11 not previously associated) after further adjustments for BMI and fasting plasma glucose. Of these, 144 and 68 associations, respectively, replicated in a multiethnic cohort. Among these is an apparently novel isomer of the 1-deoxyceramide Cer(m18:1/24:0) with functional geonomics and high-resolution mass spectrometry. Overall, known and unknown metabolites provided complementary information (median correlation ρ = 0.29), and their inclusion with clinical risk factors improved diabetes prediction modeling. Our findings highlight the importance of including nontargeted metabolomics methods to provide new insights into diabetes development in ethnically diverse cohorts.
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spelling pubmed-96300882023-01-21 Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans Chen, Zsu-Zsu Pacheco, Julian Avila Gao, Yan Deng, Shuliang Peterson, Bennet Shi, Xu Zheng, Shuning Tahir, Usman A. Katz, Daniel H. Cruz, Daniel E. Ngo, Debby Benson, Mark D. Robbins, Jeremy M. Guo, Xiuqing del Rocio Sevilla Gonzalez, Magdalena Manning, Alisa Correa, Adolfo Meigs, James B. Taylor, Kent D. Rich, Stephen S. Goodarzi, Mark O. Rotter, Jerome I. Wilson, James G. Clish, Clary B. Gerszten, Robert E. Diabetes Genetics/Genomes/Proteomics/Metabolomics Nontargeted metabolomics methods have increased potential to identify new disease biomarkers, but assessments of the additive information provided in large human cohorts by these less biased techniques are limited. To diversify our knowledge of diabetes-associated metabolites, we leveraged a method that measures 305 targeted or “known” and 2,342 nontargeted or “unknown” compounds in fasting plasma samples from 2,750 participants (315 incident cases) in the Jackson Heart Study (JHS)—a community cohort of self-identified African Americans—who are underrepresented in omics studies. We found 307 unique compounds (82 known) associated with diabetes after adjusting for age and sex at a false discovery rate of <0.05 and 124 compounds (35 known, including 11 not previously associated) after further adjustments for BMI and fasting plasma glucose. Of these, 144 and 68 associations, respectively, replicated in a multiethnic cohort. Among these is an apparently novel isomer of the 1-deoxyceramide Cer(m18:1/24:0) with functional geonomics and high-resolution mass spectrometry. Overall, known and unknown metabolites provided complementary information (median correlation ρ = 0.29), and their inclusion with clinical risk factors improved diabetes prediction modeling. Our findings highlight the importance of including nontargeted metabolomics methods to provide new insights into diabetes development in ethnically diverse cohorts. American Diabetes Association 2022-11 2022-08-23 /pmc/articles/PMC9630088/ /pubmed/35998269 http://dx.doi.org/10.2337/db22-0033 Text en © 2022 by the American Diabetes Association https://www.diabetesjournals.org/journals/pages/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/journals/pages/license.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Chen, Zsu-Zsu
Pacheco, Julian Avila
Gao, Yan
Deng, Shuliang
Peterson, Bennet
Shi, Xu
Zheng, Shuning
Tahir, Usman A.
Katz, Daniel H.
Cruz, Daniel E.
Ngo, Debby
Benson, Mark D.
Robbins, Jeremy M.
Guo, Xiuqing
del Rocio Sevilla Gonzalez, Magdalena
Manning, Alisa
Correa, Adolfo
Meigs, James B.
Taylor, Kent D.
Rich, Stephen S.
Goodarzi, Mark O.
Rotter, Jerome I.
Wilson, James G.
Clish, Clary B.
Gerszten, Robert E.
Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans
title Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans
title_full Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans
title_fullStr Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans
title_full_unstemmed Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans
title_short Nontargeted and Targeted Metabolomic Profiling Reveals Novel Metabolite Biomarkers of Incident Diabetes in African Americans
title_sort nontargeted and targeted metabolomic profiling reveals novel metabolite biomarkers of incident diabetes in african americans
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630088/
https://www.ncbi.nlm.nih.gov/pubmed/35998269
http://dx.doi.org/10.2337/db22-0033
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