Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood
Summary: Background: Cardiovascular diseases may originate in childhood. Biomarkers identifying individuals with increased risk for disease are needed to support early detection and to optimise prevention strategies. Methods: In this prospective study, by applying a machine learning to high through...
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Elsevier
2021-10-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421004047 |
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English |
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Article |
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DOAJ |
author |
Xiaowei Ojanen, Ph.D Runtan Cheng, Msc Timo Törmäkangas, Ph.D Noa Rappaport, Ph.D Tomasz Wilmanski, Ph.D Na Wu, Msc Erik Fung, M.B.Ch.B., Ph.D Rozenn Nedelec, MSc Sylvain Sebert, PhD Dimitris Vlachopoulos, Ph.D Wei Yan, Ph.D Nathan D. Price, Ph.D Sulin Cheng, Ph.D Petri Wiklund, Ph.D |
spellingShingle |
Xiaowei Ojanen, Ph.D Runtan Cheng, Msc Timo Törmäkangas, Ph.D Noa Rappaport, Ph.D Tomasz Wilmanski, Ph.D Na Wu, Msc Erik Fung, M.B.Ch.B., Ph.D Rozenn Nedelec, MSc Sylvain Sebert, PhD Dimitris Vlachopoulos, Ph.D Wei Yan, Ph.D Nathan D. Price, Ph.D Sulin Cheng, Ph.D Petri Wiklund, Ph.D Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood EBioMedicine metabolomics cardio-metabolic risk children longitudinal-study ALSPAC |
author_facet |
Xiaowei Ojanen, Ph.D Runtan Cheng, Msc Timo Törmäkangas, Ph.D Noa Rappaport, Ph.D Tomasz Wilmanski, Ph.D Na Wu, Msc Erik Fung, M.B.Ch.B., Ph.D Rozenn Nedelec, MSc Sylvain Sebert, PhD Dimitris Vlachopoulos, Ph.D Wei Yan, Ph.D Nathan D. Price, Ph.D Sulin Cheng, Ph.D Petri Wiklund, Ph.D |
author_sort |
Xiaowei Ojanen, Ph.D |
title |
Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood |
title_short |
Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood |
title_full |
Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood |
title_fullStr |
Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood |
title_full_unstemmed |
Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood |
title_sort |
towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthood |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2021-10-01 |
description |
Summary: Background: Cardiovascular diseases may originate in childhood. Biomarkers identifying individuals with increased risk for disease are needed to support early detection and to optimise prevention strategies. Methods: In this prospective study, by applying a machine learning to high throughput NMR-based metabolomics data, we identified circulating childhood metabolic predictors of adult cardiovascular disease risk (MetS score) in a cohort of 396 females, followed from childhood (mean age 11·2 years) to early adulthood (mean age 18·1 years). The results obtained from the discovery cohort were validated in a large longitudinal birth cohort of females and males followed from puberty to adulthood (n = 2664) and in four cross-sectional data sets (n = 6341). Findings: The identified childhood metabolic signature included three circulating biomarkers, glycoprotein acetyls (GlycA), large high-density lipoprotein phospholipids (L-HDL-PL), and the ratio of apolipoprotein B to apolipoprotein A-1 (ApoB/ApoA) that were associated with increased cardio-metabolic risk in early adulthood (AUC = 0·641‒0·802, all p<0·01). These associations were confirmed in all validation cohorts with similar effect estimates both in females (AUC = 0·667‒0·905, all p<0·01) and males (AUC = 0·734‒0·889, all p<0·01) as well as in elderly patients with and without type 2 diabetes (AUC = 0·517‒0·700, all p<0·01). We subsequently applied random intercept cross-lagged panel model analysis, which suggested bidirectional causal relationship between metabolic biomarkers and cardio-metabolic risk score from childhood to early adulthood. Interpretation: These results provide evidence for the utility of a circulating metabolomics panel to identify children and adolescents at risk for future cardiovascular disease, to whom preventive measures and follow-up could be indicated. |
topic |
metabolomics cardio-metabolic risk children longitudinal-study ALSPAC |
url |
http://www.sciencedirect.com/science/article/pii/S2352396421004047 |
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doaj-cf456c54ccaa46fc829bae1d6626b23e2021-10-09T04:39:42ZengElsevierEBioMedicine2352-39642021-10-0172103611Towards early risk biomarkers: serum metabolic signature in childhood predicts cardio-metabolic risk in adulthoodXiaowei Ojanen, Ph.D0Runtan Cheng, Msc1Timo Törmäkangas, Ph.D2Noa Rappaport, Ph.D3Tomasz Wilmanski, Ph.D4Na Wu, Msc5Erik Fung, M.B.Ch.B., Ph.D6Rozenn Nedelec, MSc7Sylvain Sebert, PhD8Dimitris Vlachopoulos, Ph.D9Wei Yan, Ph.D10Nathan D. Price, Ph.D11Sulin Cheng, Ph.D12Petri Wiklund, Ph.D13Key Laboratory of Systems Biomedicine (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, FinlandKey Laboratory of Systems Biomedicine (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, ChinaFaculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, FinlandInstitute for Systems Biology, Seattle, WA, USAInstitute for Systems Biology, Seattle, WA, USAKey Laboratory of Systems Biomedicine (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaCARE Programme, Lui Che Woo Institute of Innovative Medicine, CUHK Hong Kong Hub of Paediatric Excellence, Hong Kong Children's Hospital, Hong Kong SAR, China; Laboratory for Heart Failure + Circulation Research, Li Ka Shing Institute of Health Sciences; Gerald Choa Cardiac Research Centre, Department of Medicine and Therapeutics; Centre for Cardiovascular Genomics and Medicine, Faculty of Medicine, The Chinese University of Hong Kong and Prince of Wales Hospital, Hong Kong SAR, China; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United KingdomCentre for Life-Course Health Research, Faculty of Medicine, University of Oulu, FinlandCentre for Life-Course Health Research, Faculty of Medicine, University of Oulu, FinlandChildren's Health and Exercise Research Centre, Sport and Health Sciences, University of Exeter, Exeter, United KingdomKey Laboratory of Systems Biomedicine (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, ChinaInstitute for Systems Biology, Seattle, WA, USAKey Laboratory of Systems Biomedicine (Ministry of Education), School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland; Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China; Corresponding author and requests for reprints to: Dr. Petri Wiklund and Dr. Sulin ChengExercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland; Corresponding author and requests for reprints to: Dr. Petri Wiklund and Dr. Sulin ChengSummary: Background: Cardiovascular diseases may originate in childhood. Biomarkers identifying individuals with increased risk for disease are needed to support early detection and to optimise prevention strategies. Methods: In this prospective study, by applying a machine learning to high throughput NMR-based metabolomics data, we identified circulating childhood metabolic predictors of adult cardiovascular disease risk (MetS score) in a cohort of 396 females, followed from childhood (mean age 11·2 years) to early adulthood (mean age 18·1 years). The results obtained from the discovery cohort were validated in a large longitudinal birth cohort of females and males followed from puberty to adulthood (n = 2664) and in four cross-sectional data sets (n = 6341). Findings: The identified childhood metabolic signature included three circulating biomarkers, glycoprotein acetyls (GlycA), large high-density lipoprotein phospholipids (L-HDL-PL), and the ratio of apolipoprotein B to apolipoprotein A-1 (ApoB/ApoA) that were associated with increased cardio-metabolic risk in early adulthood (AUC = 0·641‒0·802, all p<0·01). These associations were confirmed in all validation cohorts with similar effect estimates both in females (AUC = 0·667‒0·905, all p<0·01) and males (AUC = 0·734‒0·889, all p<0·01) as well as in elderly patients with and without type 2 diabetes (AUC = 0·517‒0·700, all p<0·01). We subsequently applied random intercept cross-lagged panel model analysis, which suggested bidirectional causal relationship between metabolic biomarkers and cardio-metabolic risk score from childhood to early adulthood. Interpretation: These results provide evidence for the utility of a circulating metabolomics panel to identify children and adolescents at risk for future cardiovascular disease, to whom preventive measures and follow-up could be indicated.http://www.sciencedirect.com/science/article/pii/S2352396421004047metabolomicscardio-metabolic riskchildrenlongitudinal-studyALSPAC |