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dc.contributor.authorWang, Q-
dc.contributor.authorNiironen, M-
dc.contributor.authorTynkkynen, T-
dc.contributor.authorTiainen, M-
dc.contributor.authorDrenos, F-
dc.contributor.authorKangas, AJ-
dc.contributor.authorSoininen, P-
dc.contributor.authorSkilton, MR-
dc.contributor.authorHeikkilä, K-
dc.contributor.authorPouta, A-
dc.contributor.authorKähönen, M-
dc.contributor.authorLehtimäki, T-
dc.contributor.authorRose, RJ-
dc.contributor.authorKajantie, E-
dc.contributor.authorPerola, M-
dc.contributor.authorKaprio, J-
dc.contributor.authorEriksson, JG-
dc.contributor.authorRaitakari, OT-
dc.contributor.authorLawlor, DA-
dc.contributor.authorDavey Smith, G-
dc.contributor.authorJärvelin, M-R-
dc.contributor.authorAla-Korpela, M-
dc.contributor.authorAuro, K-
dc.identifier.citationInternational Journal of Epidemiology, 2016, 45 (5), pp. 1539 - 1550en_US
dc.description.abstractbstract Background: Lower birthweight is associated with increased susceptibility to cardiome-tabolic diseases in adulthood, but the underlying molecular pathways are incompletely understood. We examined associations of birthweight with a comprehensive metabolic profile measured in adolescents and adults. Methods: High-throughput nuclear magnetic resonance metabolomics and biochemical assays were used to quantify 87 circulating metabolic measures in seven cohorts from Finland and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15–75). Metabolic associations with birthweight were assessed by linear regression mod-els adjusted for sex, gestational age and age at blood sampling. The metabolic associ-ations with birthweight were compared with the corresponding associations with adult body mass index (BMI). Results: Lower birthweight adjusted for gestational age was adversely associated with cardiometabolic biomarkers, including lipoprotein subclasses, fatty acids, amino acids and markers of inflammation and impaired liver function (P < 0.0015 for 46 measures). Associations were consistent across cohorts with different ages at metabolic profiling, but the magnitudes were weak. The pattern of metabolic deviations associated with lower birthweight resembled the metabolic signature of higher adult BMI (R2 ¼ 0.77) as-sessed at the same time as the metabolic profiling. The resemblance indicated that 1 kg lower birthweight is associated with similar metabolic aberrations as caused by 0.92 units higher BMI in adulthood. Conclusions: Lower birthweight adjusted for gestational age is associated with adverse biomarker aberrations across multiple metabolic pathways. Coherent metabolic signatures between lower birthweight and higher adult adiposity suggest that shared molecular pathways may potentially underpin the metabolic deviations. However, the magnitudes of metabolic associations with birthweight are modest in comparison to the effects of adiposity, implying that birthweight is only a weak indicator of the metabolic risk profile in adulthood.en_US
dc.description.sponsorshipFunding This study was supported by the Strategic Research Funding from the University of Oulu, Finland, the Sigrid Juselius Foundation, the Novo Nordisk Foundation, the Yrjo¨ Jahnsson Foundation, the Finnish Diabetes Research Foundation, the Finnish Medical Foundation, the Paulo Foundation, Biocenter Oulu, Finland, and the UK Medical Research Council via the University of Bristol Integrative Epidemiology Unit (IEU; MC_UU_12013/1 and MC_UU_12013/5). The Cardiovascular Risk in Young Finns Study is supported by the Academy of Finland (grants 286284, 134309, 126925, 121584, 124282, 129378, 117787 and 41071), Finnish Foundation for Cardiovascular Research, Oulu, Helsinki, Kuopio, Tampere, and Turku University Central Hospital Medical Funds, the Paavo Nurmi Foundation, the Juho Vainio Foundation, the Finnish Cultural Foundation and the Finnish Funding Agency for Technology and Innovation. The Northern Finland Birth Cohorts of 1966 and 1986 have received financial support from Academy of Finland, University Hospital Oulu, Biocenter Oulu, University of Oulu, the European Commission (EURO-BLCS, Framework 5 Award QLG1-CT-2000-01643, ENGAGE project and grant agree-ment HEALTH-F4-2007-201413, EurHEALTHAgeing (277849), European Regional Developmental Fund), EU H2020-PHC-2014 (grant no. 633595), DynaHEALTH, NHLBI grant 5R01HL087679-02 through the STAMPEED programme (1RL1MH083268-01), NIH/NIMH (5R01MH63706:02), Stanley Foundation, the UK Medical Research Council and Wellcome Trust. The UK Medical Research Council and Wellcome Trust (grant: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. The con-tribution of D.A.L to this study is supported by grants from the US National Institute of Health (R01 DK10324), European Research Council (ObesityDevelop: grant no. 669545) and UK National Institute for Health Research (NF-SI-0166-10196). F.D., D.A.L., G.D.S. and M.A.K. work in a Unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1 and MC_UU_12013/5). The FinnTwin-12 and FinnTwin-16 studies have received support from the National Institute on Alcohol Abuse and Alcoholism (R37-AA12502, R01-AA09203 and K05-AA00145). The views expressed in this paper are those of the authors and not necessarily any funding body. Conflict of interest: P.W., A.J.K., P.S. and M.A.K. are shareholders of Brainshake Ltd, a company offering NMR-based metabolic profiling ( P.W., T.T., M.T., P.S. and A.J.K. re-port employment relation with Brainshake Ltd. D.A.L. has received funding for biomarker research, unrelated to this paper, from Roche Diagnostics and Ferring Pharmaceuticals. K.A. is currently em-ployed by GSK. No other authors reported disclosures.en_US
dc.format.extent1539 - 1550-
dc.subjectFetal programming,en_US
dc.subjectmetabolic signatures,en_US
dc.subjectfatty acidsen_US
dc.subject, amino acidsen_US
dc.titleMetabolic signatures of birthweight in 18 288 adolescents and adultsen_US
dc.relation.isPartOfInternational Journal of Epidemiology-
Appears in Collections:Dept of Clinical Sciences Research Papers

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