| 1. |
- Lind, Lars, et al.
(författare)
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Multicohort Metabolomics Analysis Discloses 9-Decenoylcarnitine to Be Associated With Incident Atrial Fibrillation
- 2021
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980 .- 2047-9980. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Salihovic, Samira, 1985-, et al.
(författare)
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Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances
- 2019
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Ingår i: Journal of Exposure Science and Environmental Epidemiology. - : Nature Publishing Group. - 1559-0631 .- 1559-064X. ; 29:2, s. 196-205
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Tidskriftsartikel (refereegranskat)abstract
- Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004. PFASs were analyzed in plasma using isotope-dilution ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Non-target metabolomics profiling was performed in plasma using UPLC coupled to time-of-flight mass spectrometry (UPLC-QTOFMS) operated in positive electrospray mode. Multivariate linear regression analysis was used to investigate associations between circulating levels of PFASs and metabolites. In total, 15 metabolites, predominantly from lipid pathways, were associated with levels of PFASs following adjustment for sex, smoking, exercise habits, education, energy, and alcohol intake, after correction for multiple testing. Perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) were strongly associated with multiple glycerophosphocholines and fatty acids including docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). We also found that the different PFASs evaluated were associated with distinctive metabolic profiles, suggesting potentially different biochemical pathways in humans.
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| 3. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Non-targeted urine metabolomics and associations with prevalent and incident type 2 diabetes
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Better risk prediction and new molecular targets are key priorities in type 2 diabetes (T2D) research. Little is known about the role of the urine metabolome in predicting the risk of T2D. We aimed to use non-targeted urine metabolomics to discover biomarkers and improve risk prediction for T2D. Urine samples from two community cohorts of 1,424 adults were analyzed by ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). In a discovery/replication design, three out of 62 annotated metabolites were associated with prevalent T2D, notably lower urine levels of 3-hydroxyundecanoyl-carnitine. In participants without diabetes at baseline, LASSO regression in the training set selected six metabolites that improved prediction of T2D beyond established risk factors risk over up to 12 years' follow-up in the test sample, from C-statistic 0.866 to 0.892. Our results in one of the largest non-targeted urinary metabolomics study to date demonstrate the role of the urine metabolome in identifying at-risk persons for T2D and suggest urine 3-hydroxyundecanoyl-carnitine as a biomarker candidate.
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| 4. |
- Salihovic, Samira, 1985-, et al.
(författare)
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The metabolic fingerprint of p,p'-DDE and HCB exposure in humans
- 2016
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 88, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dichlorodiphenyldichloroethylene (p,p'-DDE) and hexachlorobenzene (HCB) are organochlorine pesticides with well-known endocrine disrupting properties. Exposure to p,p'-DDE and HCB concerns human populations worldwide and has been linked to metabolic disorders such as obesity and type 2 diabetes, but details about these associations in humans from the general population are largely unknown.Objectives: We investigated the associations between p,p'-DDE and HCB exposure and global metabolomic profiles in serum samples from 1016 participants from the Swedish population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.Methods: HCB and p,p'-DDE levels were determined using gas chromatography coupled to high-resolution mass spectrometry (GC-HRMS). Metabolite levels were determined by using a non-targeted metabolomics approach with ultra-performance liquid chromatography coupled to time-of- flight mass spectrometry (UPLC-TOFMS). Association analyses were performed using multivariate linear regression.Results: We found circulating levels of p,p-DDE and HCB to be significantly associated with circulating levels of 16 metabolites following adjustment for age, sex, education level, exercise habits, smoking, energy intake, and alcohol intake. The majority of the 16 metabolites belong to lipid metabolism pathways and include fatty acids, glycerophospholipids, sphingolipids, and glycerolipids. Overall, p,p'-DDE and HCB levels were found to be correlated to different metabolites, which suggests that different metabolic fingerprints may be related to circulating levels of these two pesticides.Conclusions: Our findings establish a link between human exposure to organochlorine pesticides and metabolites of key metabolic processes mainly related to human lipid metabolism.
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