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Multicohort Metabol...
Multicohort Metabolomics Analysis Discloses 9-Decenoylcarnitine to Be Associated With Incident Atrial Fibrillation
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- Lind, Lars (author)
- Uppsala universitet,Klinisk epidemiologi
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- Salihovic, Samira, Associate Senior Lecturer, 1985- (author)
- Uppsala universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,School of Medical Sciences, Örebro University, Örebro, Sweden
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- Sundström, Johan, Professor, 1971- (author)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk epidemiologi
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- Broeckling, Corey D. (author)
- Proteomics and Metabolomics Facility, Colorado State University, Fort Collins, CO, USA
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- Magnusson, Patrik K. (author)
- Karolinska Institutet
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- Prenni, Jessica (author)
- Department of Horticulture and Landscape Architecture, Colorado State University, Fort Collins, CO, USA
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- Fall, Tove, 1979- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi
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- Ärnlöv, Johan, 1970- (author)
- Högskolan Dalarna,Medicinsk vetenskap,Karolinska Institutet
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(creator_code:org_t)
- Wiley-Blackwell Publishing Inc. 2021
- 2021
- English.
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In: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 10:2
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Atrial fibrillation
- carnitine
- epidemiology
- gene
- metabolomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lind, Lars
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Salihovic, Samir ...
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Sundström, Johan ...
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Broeckling, Core ...
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Magnusson, Patri ...
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Prenni, Jessica
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Fall, Tove, 1979 ...
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Ärnlöv, Johan, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Journal of the A ...
- By the university
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Örebro University
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Högskolan Dalarna
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Uppsala University
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Karolinska Institutet