A1 Refereed original research article in a scientific journal
Understanding lipidomics associations and the lipoprotein-related caveats in population epidemiology
Authors: Zhao, Siyu; Ohukainen, Pauli; Kettunen, Johannes; Järvelin, Marjo-Riitta; Kähönen, Mika; Lehtimäki, Terho; Viikari, Jorma; Raitakari, Olli T; Mäkinen, Ville-Petteri; Ala-Korpela, Mika
Publisher: Oxford University Press
Publication year: 2024
Journal: American Journal of Epidemiology
ISSN: 0002-9262
DOI: https://doi.org/10.1093/aje/kwae445
Web address : https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwae445/7912636
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/477982286
Mass spectrometry lipidomics is becoming customary to analyse serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known on the consequences of adjusting lipidomics data with lipoprotein measures. We studied two population cohorts with 5,657 and 2,036 participants. LC-MS/MS lipidomics was applied to analyse 24 molecular lipid classes and NMR spectroscopy to quantify seven lipoprotein lipids plus apolipoprotein A-I (apoA-I) and B (apoB). The associations of these measures were analysed via partial Spearman's correlations. The effects of nine different lipoprotein adjustments on these interrelationships were assessed. Multivariable regression modelling with these adjustments was also performed for the associations between the lipidomics data and BMI. These novel large-scale lipidomics data and their associations between the lipoprotein measures were coherent in both population cohorts, confirming the compatibility of the analytical approaches. Simulated data were generated to corroborate the mediation effects. The lipoprotein-related lipid-transport and metabolism inherently mediate the lipidomics associations as evident from the striking effects of the lipoprotein adjustments. These effects and their relevance to the interpretations of lipidomics data are presented and discussed in detail for the first time. The combined lipoprotein lipid adjustments appear prone to overadjustment and arbitrary biases.
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Funding information in the publication:
The NFBC has been supported, for instance, by EU, Academy of Finland, PREcisE, Joint Programming Initiative a Healthy Diet for a Healthy Life (no. 655), UK Medical Research Council, Biotechnology and Biological Sciences Research Council (MR/S03658X/1), and European Regional Development Fund Grant no. 539/2010 A31592. The Young Finns Study has been financially supported by the Academy of Finland: grants 356405, 322098, 286284,
134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117797 (Gendi), and 141071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); European Research Council (grant 742927 for MULTIEPIGEN project); Tampere University Hospital Supporting Foundation; Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; BETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink and the Jane and Aatos Erkko Foundation. M.A.-K. was supported by a research grant from the Sigrid Juselius Foundation, the Finnish Foundation for Cardiovascular Research, and the Research
Council of Finland (grant no. 357183).
