Metabolomics reveals a link between homocysteine and lipid metabolism and leukocyte telomere length: the ENGAGE consortium.
journal contribution
posted on 2019-10-24, 08:37 authored by A van der Spek, L Broer, HHM Draisma, R Pool, E Albrecht, M Beekman, M Mangino, M Raag, DR Nyholt, HK Dharuri, V Codd, N Amin, EJC de Geus, J Deelen, A Demirkan, I Yet, K Fischer, T Haller, AK Henders, A Isaacs, SE Medland, GW Montgomery, SP Mooijaart, K Strauch, HED Suchiman, AAM Vaarhorst, D van Heemst, R Wang-Sattler, JB Whitfield, G Willemsen, MJ Wright, NG Martin, NJ Samani, A Metspalu, P Eline Slagboom, TD Spector, DI Boomsma, CM van Duijn, C GiegerTelomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.
Funding
KORA: KORA was financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFN; NGFNPlus, project number 01GS0834) and supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. Telomere assays were funded by the ENGAGE consortium. NTR: We thank all participants in the Netherlands Twin Register. Research was funded by the Netherlands Organization for Scientific Research (NWO: MagW/ZonMW grants 904-61-090, 985-10-002,904-61-193,480-04-004, 400-05-717, Addiction-31160008 Middelgroot-911-09-032, Spinozapremie 56-464-14192), Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007), the VU University’s Institute for Health and Care Research (EMGO+), the European Community’s Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413) and the European Science Council (ERC - 230374 and ERC-284167). Harmen H.M. Draisma is funded by the Wellcome Trust (WT205915). EGCUT: EGCUT was supported by Estonian Research Council [IUT20-60, IUT24-6 and PUT1665 to K.F.]; European Union Horizon 2020 [692145 and European Union through the European Regional Development Fund [2014-2020.4.01.15-0012 GENTRANSMED]. We also thank all participants of the Estonian Biobank cohort. EGCUT studies were financed by University of Tartu (grant “Center of Translational Genomics”), by Estonian Goverment (grant #SF0180142s08, grant #ETF9353) and by European Commission through the European Regional Development Fund in the frame of grant “Centre of Excellence in Genomics” and Estonian Research Infrastructure’s Roadmap and through FP7 grant #313010. TwinsUK: The study was funded by the Wellcome Trust; European Com
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Scientific Reports, 2019, volume 9, Article number: 11623Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular SciencesVersion
- VoR (Version of Record)
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Scientific ReportsPublisher
Nature Research (part of Springer Nature)eissn
2045-2322Acceptance date
2019-06-26Copyright date
2019Available date
2019-10-24Publisher DOI
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https://www.nature.com/articles/s41598-019-47282-6Notes
Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-47282-6.Language
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