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A combined observational and Mendelian randomization investigation reveals NMR-measured analytes to be risk factors of major cardiovascular diseases
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.ORCID iD: 0000-0003-2891-9273
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.ORCID iD: 0000-0003-2335-8542
2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 10645Article in journal (Refereed) Published
Abstract [en]

Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.

Place, publisher, year, edition, pages
Springer Nature, 2024. Vol. 14, no 1, article id 10645
Keywords [en]
NMR, Lipoproteins, Cardiovascular diseases, UK Biobank, Mendelian randomization
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-528687DOI: 10.1038/s41598-024-61440-5ISI: 001217905100068PubMedID: 38724583OAI: oai:DiVA.org:uu-528687DiVA, id: diva2:1863562
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Uppsala UniversityAvailable from: 2024-05-31 Created: 2024-05-31 Last updated: 2024-05-31Bibliographically approved

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Zheng, RuiLind, Lars

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