Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent

Introduction We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults.Research design and methods We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600)...

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Main Authors: Cynthia M Pérez, Jose M Ordovas, Katherine L Tucker, Shilpa N Bhupathiraju, Meir J Stampfer, Dong D Wang, Liming Liang, Chao-Qiang Lai, Rachel S Kelly, David T W Wong, Clary B Clish, Danielle E Haslam, Clemens Wittenbecher, Marijulie Martínez, Chih-Hao Lee, Laurence D Parnell, Kaumudi J Joshipura
Format: Article
Language:English
Published: BMJ Publishing Group 2021-03-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/9/1/e002298.full
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author Cynthia M Pérez
Jose M Ordovas
Katherine L Tucker
Shilpa N Bhupathiraju
Meir J Stampfer
Dong D Wang
Liming Liang
Chao-Qiang Lai
Rachel S Kelly
David T W Wong
Clary B Clish
Danielle E Haslam
Clemens Wittenbecher
Marijulie Martínez
Chih-Hao Lee
Laurence D Parnell
Kaumudi J Joshipura
author_facet Cynthia M Pérez
Jose M Ordovas
Katherine L Tucker
Shilpa N Bhupathiraju
Meir J Stampfer
Dong D Wang
Liming Liang
Chao-Qiang Lai
Rachel S Kelly
David T W Wong
Clary B Clish
Danielle E Haslam
Clemens Wittenbecher
Marijulie Martínez
Chih-Hao Lee
Laurence D Parnell
Kaumudi J Joshipura
author_sort Cynthia M Pérez
collection DOAJ
description Introduction We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults.Research design and methods We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40–75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates.Results Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS.Conclusions Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.
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spelling doaj-art-ead595bcd8b54bd5924e5e7694cc4b7f2025-08-20T01:59:04ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972021-03-019110.1136/bmjdrc-2021-002298Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descentCynthia M Pérez0Jose M Ordovas1Katherine L Tucker2Shilpa N Bhupathiraju3Meir J Stampfer4Dong D Wang5Liming Liang6Chao-Qiang Lai7Rachel S Kelly8David T W Wong9Clary B Clish10Danielle E Haslam11Clemens Wittenbecher12Marijulie Martínez13Chih-Hao Lee14Laurence D Parnell15Kaumudi J Joshipura16Department of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto RicoIMDEA-Food Institute, CEI UAM+CSIC, Madrid, SpainDepartment of Biomedical and Nutritional Sciences and Center for Population Health, University of Massachusetts Lowell, Lowell, Massachusetts, USAresearch associateprofessor of medicine and epidemiologyChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USADepartment of Biostatistics, Harvard University T H Chan School of Public Health, Boston, Massachusetts, USAAgricultural Research Service, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USAChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA1 UCLA School of Dentistry, Los Angeles, California, USAMetabolomics Platform, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USAChanning Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USANutrition, Harvard T H Chan School of Public Health, Boston, Massachusetts, USACenter for Clinical Research and Health Promotion, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto RicoMolecular Metabolism, Harvard T H Chan School of Public Health, Boston, Massachusetts, USAAgricultural Research Service, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts, USAEpidemiology, Harvard T H Chan School of Public Health, Boston, Massachusetts, USAIntroduction We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults.Research design and methods We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40–75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates.Results Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS.Conclusions Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.https://drc.bmj.com/content/9/1/e002298.full
spellingShingle Cynthia M Pérez
Jose M Ordovas
Katherine L Tucker
Shilpa N Bhupathiraju
Meir J Stampfer
Dong D Wang
Liming Liang
Chao-Qiang Lai
Rachel S Kelly
David T W Wong
Clary B Clish
Danielle E Haslam
Clemens Wittenbecher
Marijulie Martínez
Chih-Hao Lee
Laurence D Parnell
Kaumudi J Joshipura
Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent
BMJ Open Diabetes Research & Care
title Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent
title_full Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent
title_fullStr Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent
title_full_unstemmed Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent
title_short Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent
title_sort associations of network derived metabolite clusters with prevalent type 2 diabetes among adults of puerto rican descent
url https://drc.bmj.com/content/9/1/e002298.full
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