Abstract
Population-scale expression profiling studies can provide valuable insights into biological and disease-underlying mechanisms. The availability of phenotypic traits is essential for studying clinical effects. Therefore, missing, incomplete, or inaccurate phenotypic information can make analyses challenging and prevent RNA-seq or other omics data to be reused. A possible solution are predictors that infer clinical or behavioral phenotypic traits from molecular data. While such predictors have been developed based on different omics data types and are being applied in various studies, metabolomics-based surrogates are less commonly used than predictors based on DNA methylation profiles.In this study, we inferred 17 traits, including diabetes status and exposure to lipid medication, using previously trained metabolomic predictors. We evaluated whether these metabolomic surrogates can be used as an alternative to reported information for studying the respective phenotypes using expression profiling data of four population cohorts. For the majority of the 17 traits, the metabolomic surrogates performed similarly to the reported phenotypes in terms of effect sizes, number of significant associations, replication rates, and significantly enriched pathways.The application of metabolomics-derived surrogate outcomes opens new possibilities for reuse of multi-omics data sets. In studies where availability of clinical metadata is limited, missing or incomplete information can be complemented by these surrogates, thereby increasing the size of available data sets. Additionally, the availability of such surrogates could be used to correct for potential biological confounding. In the future, it would be interesting to further investigate the use of molecular predictors across different omics types and cohorts.
| Original language | English |
|---|---|
| Article number | 546 |
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | BMC Genomics |
| Volume | 23 |
| Early online date | 31 Jul 2022 |
| DOIs | |
| Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:© 2022, The Author(s).
Funding
AJG and PACH received funding from EATRIS-Plus [], which has received funding from the European Union’s Horizon 2020 research and innovation programme [] under grant agreement no. 871096, and The Netherlands X-omics Initiative [], which is (partly) funded by the Dutch Research Council [], project no. 184.034.019. The Biobank-based Integrative Omics Study (BIOS) Consortium [] and the BBMRI Metabolomics Consortium [] are funded by BBMRI-NL, a Research Infrastructure financed by NWO, project nos. 184.021.007 and 184033111. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank the biobanks and participants of LifeLines [53], the Leiden Longevity Study [54], the Netherlands Twin Register [55], and the Rotterdam Study [56]. Special thanks also to Leon Mei, Davy Cats, Martin Brandt and the SURF RSC Team for their support and management of data and computational infrastructure. BBMRI-NL BIOS consortium Management Team Bastiaan T. Heijmans (chair)3, Peter A.C. ’t Hoen7, Joyce van Meurs8, Rick Jansen10, Lude Franke11. Cohort collection Dorret I. Boomsma12, RenÉ Pool12, Jenny van Dongen12, Jouke J. Hottenga12(Netherlands Twin Register); Marleen M.J. van Greevenbroek13, Coen D.A. Stehouwer13, Carla J.H. van der Kallen13, Casper G. Schalkwijk13(Cohort study on Diabetes and Atherosclerosis Maastricht); Cisca Wijmenga11, Lude Franke11, Sasha Zhernakova11, Ettje F. Tigchelaar11(LifeLines Deep); P. Eline Slagboom3, Marian Beekman3, Joris Deelen3, Diana van Heemst14(Leiden Longevity Study); Jan H. Veldink15, Leonard H. van den Berg15(Prospective ALS Study Netherlands); Cornelia M. van Duijn9, Bert A. Hofman16, Aaron Isaacs9, AndrÉ G. Uitterlinden8(Rotterdam Study). Data generation Joyce van Meurs (Chair)8, P. Mila Jhamai8, Michael Verbiest8, H. Eka D. Suchiman3, Marijn Verkerk8, Ruud van der Breggen3, Jeroen van Rooij8, Nico Lakenberg3. Data management and computational infrastructure Hailiang Mei (Chair)17, Maarten van Iterson3, Michiel van Galen7, Jan Bot18, Dasha V. Zhernakova11, Rick Jansen10, Peter van ’t Hof17, Patrick Deelen11, Irene Nooren18, Peter A.C. ’t Hoen7, Bastiaan T. Heijmans3, Matthijs Moed3. Data analysis group Lude Franke (Co-Chair)11, Martijn Vermaat7, Dasha V. Zhernakova11, RenÉ Luijk3, Marc Jan Bonder11, Maarten van Iterson3, Patrick Deelen11, Freerk van Dijk19, Michiel van Galen7, Wibowo Arindrarto17, Szymon M. Kielbasa20, Morris A. Swertz19, Erik. W van Zwet20, Rick Jansen10, Peter-Bram ’t Hoen (Co-Chair)7, Bastiaan T. Heijmans (Co-Chair)3. Affiliations of BIOS members3Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.7Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.8Department of Internal Medicine, ErasmusMC, Rotterdam, The Netherlands.9Department of Genetic Epidemiology, ErasmusMC, Rotterdam, The Netherlands.10Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.11Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.12Department of Biological Psychology, VU University Amsterdam, Neuroscience Campus Amsterdam, Amsterdam, The Netherlands.13Department of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.14Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.15Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.16Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.17Sequence Analysis Support Core, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.18SURFsara, Amsterdam, the Netherlands.19Genomics Coordination Center, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.20Medical Statistics, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands. BBMRI-NL Metabolomics consortium Cohort collection J.M. Geleijnse21, E. Boersma22, W.E. van Spil23, M.M.J. van Greevenbroek24,25, C.D.A. Stehouwer24,25, C.J.H. van der Kallen24,25, I.C.W. Arts6,26,27, F. Rutters28,29, J.W.J. Beulens28,29, M. Muilwijk28,30, P.J.M. Elders28,30, L.M. ’t Hart28,29,31, M. Ghanbari16,32, M.A. Ikram16, M.G. Netea33, M. Kloppenburg34,35, Y.F.M. Ramos3, N. Bomer36, I. Meulenbelt3, K. Stronks37, M.B. Snijder37, A.H. Zwinderman38, B.T. Heijmans3, L.H. Lumey39, C. Wijmenga40, J. Fu40,41, A. Zhernakova40, J. Deelen6,3, S.P. Mooijaart42, M. Beekman3, P.E. Slagboom3,6, G.L.J. Onderwater43, A.M.J.M. van den Maagdenberg7,43, G.M. Terwindt43, C.Thesing44,28, M. Bot44,28, B.W.J.H. Penninx44,28, S. Trompet45,42, J.W. Jukema45, N. Sattar46, I.C.C. van der Horst47, P. van der Harst48, C. So-Osman49,50, J.A. van Hilten51, R.G.H.H. Nelissen52, I.E. Höfer53, F.W. Asselbergs54,55, P. Scheltens56, C.E. Teunissen57, W.M. van der Flier58,56, J. van Dongen44,28, R. Pool44, A.H.M. Willemsen44,28, D.I. Boomsma44,28. Sample logistics, database and catalogue H.E.D. Suchiman3, J.J.H. Barkey Wolf3, M. Beekman3, D. Cats17, H. Mei17, M. Slofstra40, M. Swertz19,40, M.J.T. Reinders4,5, E.B. van den Akker4,3. Steering committee D.I. Boomsma44,28, M.A. Ikram16, P.E. Slagboom3,6. Affiliations of BBMRI-NL Metabolomics members3Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.4Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands.5The Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands.6Max Planck Institute for Biology of Ageing, Cologne, Germany.7Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.16Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.17Sequence Analysis Support Core, Leiden University Medical Center, Leiden, the Netherlands.18SURFsara, Amsterdam, the Netherlands.19University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.21Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.22Thorax centre, Erasmus Medical Centre, Rotterdam, the Netherlands.23Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.24Department of Internal Medicine, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.25School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands.26Department of Epidemiology, Maastricht University, Maastricht, the Netherlands.27Maastricht Center for Systems Biology, Maastricht University, Maastricht, the Netherlands.28Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.29Department of Epidemiology and Biostatistics, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.30Department of General Practice and Elderly Care Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands.31Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.32Department of Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.33Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.34Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.35Department of Rheumatology, Leiden University Medical Center, The Netherlands.36Department of Experimental Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.37Department of Public Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.38Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.39Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032.40Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.41Department of Pediatrics, University Medical Center Groningen, Groningen, The Netherlands.42Department of Internal Medicine, Division of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.43Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.44Department of Biological Psychology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands.45Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.46Institute of Cardiovascular and Medical Sciences, Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.47Department of Critical Care, University Medical Center Groningen, Groningen, The Netherlands.48Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.49Sanquin Blood Bank, Leiden and Department of Haematology, Groene Hart Hospital, Gouda, the Netherlands.50International Society of Blood Transfusion (ISBT), Amsterdam, The Netherlands.51Unit of Transfusion Medicine, Sanquin Blood Bank, Leiden, The Netherlands.52Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.53Department of Clinical Chemistry and Hematology, UMC Utrecht, the Netherlands.54Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.55Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.56Department of Neurology & Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands.57Neurochemistry Laboratory, Clinical Chemistry Department, Amsterdam University Medical Center, Amsterdam Neuroscience, The Netherlands.58Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Keywords
- Clinical surrogates
- Expression profiling
- Meta-analysis
- Metabolomics
- Multi-omics
- Population cohort study
- Predictors
- Surrogate outcomes
- Surrogates
- Transcriptomics
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