Multicohort Metabolomics Analysis Discloses 9-Decenoylcarnitine to Be Associated With Incident Atrial FibrillationShow others and affiliations
2021 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, E-ISSN 2047-9980, Vol. 10, no 2, article id e017579
Article in journal (Refereed) Published
Abstract [en]
Background: The molecular mechanisms involved in atrial fibrillation are not well known. We used plasma metabolomics to investigate if we could identify novel biomarkers and pathophysiological pathways of incident atrial fibrillation.
Methods and Results: We identified 200 endogenous metabolites in plasma/serum by nontargeted ultra‐performance liquid chromatography coupled to time‐of‐flight mass spectrometry in 3 independent population‐based samples (TwinGene, n=1935, mean age 68, 43% females; PIVUS [Prospective Investigation of the Vasculature in Uppsala Seniors], n=897, mean age 70, 51% females; and ULSAM [Uppsala Longitudinal Study of Adult Men], n=1118, mean age 71, all males), with available data on incident atrial fibrillation during 10 to 12 years of follow‐up. A meta‐analysis of ULSAM and PIVUS was used as a discovery sample and TwinGene was used for validation. In PIVUS, we also investigated associations between metabolites of interest and echocardiographic indices of myocardial geometry and function. Genome‐wide association studies were performed in all 3 cohorts for metabolites of interest. In the meta‐analysis of PIVUS and ULSAM with 430 incident cases, 4 metabolites were associated with incident atrial fibrillation at a false discovery rate <5%. Of those, only 9‐decenoylcarnitine was associated with incident atrial fibrillation and replicated in the TwinGene sample (288 cases) following adjustment for traditional risk factors (hazard ratio, 1.24 per unit; 95% CI, 1.06–1.45, P=0.0061). A meta‐analysis of all 3 cohorts disclosed another 4 significant metabolites. In PIVUS, 9‐decenoylcarnitine was related to left atrium size and left ventricular mass. A Mendelian randomization analysis did not suggest a causal role of 9‐decenoylcarnitine in atrial fibrillation.
Conclusions: A nontargeted metabolomics analysis disclosed 1 novel replicated biomarker for atrial fibrillation, 9‐Decenoylcarnitine, but this acetylcarnitine is likely not causally related to atrial fibrillation.
Place, publisher, year, edition, pages
Wiley-Blackwell Publishing Inc., 2021. Vol. 10, no 2, article id e017579
Keywords [en]
Atrial fibrillation, carnitine, epidemiology, gene, metabolomics
National Category
Cardiology and Cardiovascular Disease
Identifiers
URN: urn:nbn:se:oru:diva-88429DOI: 10.1161/JAHA.120.017579ISI: 000610049900007PubMedID: 33399003Scopus ID: 2-s2.0-85099804498OAI: oai:DiVA.org:oru-88429DiVA, id: diva2:1516587
Funder
Swedish Heart Lung Foundation
Note
Funding Agency:
Uppsala University Hospital (ALF-medel)
2021-01-122021-01-122025-02-10Bibliographically approved