Tove Fall

Tove Fall
Uppsala University | UU · Department of Medical Sciences

Professor

About

264
Publications
42,803
Reads
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16,245
Citations
Introduction
I aim to identify novel predictors and causes of diabetes and cardiovascular disease using large datasets and molecular techniques analysed with state-of-the art epidemiological methods. Currently my main focus is on the metabolomic and microbiota predictors of atherosclerosis.
Additional affiliations
September 2010 - December 2012
Karolinska Institutet
Position
  • PostDoc Position
September 2005 - September 2010
Swedish University of Agricultural Sciences
Position
  • PhD Student

Publications

Publications (264)
Article
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Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this...
Article
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Aims/hypothesis Using a targeted proteomics approach, we aimed to identify and validate circulating proteins associated with impaired glucose metabolism (IGM) and type 2 diabetes in a Black South African cohort. In addition, we assessed sex-specific associations between the validated proteins and pathophysiological pathways of type 2 diabetes. Met...
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Background A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to find a metabolic profile common for all five components of MetS. Methods and findings 791 annotated non-xenobiotic metabolites were measured...
Article
Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic p...
Preprint
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. In animal models, OSA has been shown to alter the gut microbiota; however, little is known about such effects in humans. Here, we used respiratory polygraphy data from 3,570 individuals aged 50-64 from the Swedish CardioPulmonary bioImage Study (SCAPIS) and deep shotgun met...
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Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers....
Preprint
Coronary atherosclerosis is the main pathophysiological mechanism underlying myocardial infarction. The gut microbiota has been implicated in cardiometabolic disease but its relationship with subclinical coronary atherosclerosis is unknown. We identified 73 gut metagenomics species associated with coronary artery calcium score (CACS) in 8,973 SCAPI...
Preprint
Background Approximately 20% of men and 15% of women remain childless at the end of their reproductive lifespan, with childlessness increasing over time, yet we lack a comprehensive understanding of the role and relative importance of diseases associated with childlessness, particularly among men. Methods We examined all individuals born in Finlan...
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The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Here, we include data from 19,161 self-reported PCR tests to create a symptom-bas...
Article
Context There is a dispute whether obesity without major metabolic derangements may represent a benign condition or not. Objective We aimed to compare the plasma metabolome in obese subjects without the metabolic syndrome (MetS) to normal-weight subjects without MetS, as well as to obese subjects with MetS. Design Cross-sectional. Setting Two ac...
Preprint
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paragraph The human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota–host plasma metabolite interactions is...
Article
Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography c...
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Study objectives Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population-based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers...
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Objective To assess the association of cardiometabolic risk factors with hospitalisation or death due to COVID-19 in the general population. Design, setting and participants Swedish population-based cohort including 29 955 participants. Exposures Cardiometabolic risk factors assessed between 2014 and 2018. Main outcome measures Hospitalisation o...
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Inhibition of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase is associated with an increased risk of new-onset type 2 diabetes. We studied the association of genetic or pharmacological HMG-CoA reductase inhibition with plasma and adipose tissue (AT) metabolome and AT metabolic pathways. We also investigated the effects of statin-mediated pharm...
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Pyometra is one of the most common diseases in female dogs, presenting as purulent inflammation and bacterial infection of the uterus. On average 20% of intact female dogs are affected before 10 years of age, a proportion that varies greatly between breeds (3–66%). The clear breed predisposition suggests that genetic risk factors are involved in di...
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Context In a cross-sectional study, we found an association between type 2 diabetes mellitus (T2DM) and smaller bone area together with a greater bone mineral density (BMD) at the total hip. Objective To investigate these associations longitudinally, by studying T2DM status (no T2DM n=1521, incident T2DM n=119 or prevalent T2DM n=106) in relation...
Preprint
Full-text available
The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Data from 19,161 self-reported PCR tests were used to create a symptom-based mode...
Article
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Aims/hypothesis Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, smaller bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic varia...
Article
Introduction Preliminary findings suggest that pets may improve the owner’s sleep via companionship, security, physical activity, and relaxation. On the other hand, pets can disrupt the owner’s sleep. Due to the heterogeneity of the results and the low number of studies in this field, more studies with a bigger sample size are needed to explore thi...
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Preliminary findings suggest that pets may impact the owner’s sleep. By using data from the Swedish CArdioPulmonary bIoimage Study (SCAPIS) cohort, we aimed to investigate the association of pet ownership with the following self-reported sleep outcomes in 3788 to 4574 participants: (i) achieving the recommended daily sleep duration for adults (i.e....
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Background Ambulatory blood pressure monitoring (ABPM) is increasingly recommended for clinical use, but more knowledge about the prevalence and variability in ABPM-derived phenotypes in the general population is needed. We describe these parameters in the community-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. Methods We examined...
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We tested whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity, and we extended previous investigations on hospitalized pregnant women to those who did not require hospitalization. Two female community-based cohorts (18–44 years) provided longitudinal (smartphone application, N = 1,170,315, n = 79 pregnant tested...
Article
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As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed...
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A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3
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Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women...
Article
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 liqui...
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Background We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI). Methods We included 50 755 men and women from the Cohort of Swedish Men and the Swedish Mammography Cohort who answered lifestyle and medical questi...
Preprint
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Background Sufficient community testing for suspected COVID-19 regardless of residential area is essential for a successful test-trace-isolate strategy. Aim This study aimed to elucidate area level characteristics linked to testing rates. Methods Free-of-charge diagnostic tests (PCR) of SARS-CoV-2 was made available to the general public in late Ju...
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Objective To investigate whether dog and cat owners and their pets share a risk of developing diabetes. Design Cohort study. Setting Register based longitudinal study, Sweden. Participants 208 980 owner-dog pairs and 123 566 owner-cat pairs identified during a baseline assessment period (1 January 2004 to 31 December 2006). Main outcome measure...
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Background As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. Methods In this prospective, observational study, we did modelling using longitudinal, self-reported data from users of the COVI...
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Importance Higher Mediterranean diet (MED) intake has been associated with reduced risk of type 2 diabetes, but underlying biological mechanisms are unclear. Objective To characterize the relative contribution of conventional and novel biomarkers in MED-associated type 2 diabetes risk reduction in a US population. Design, Setting, and Participant...
Preprint
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Background: As many countries seek to slow the spread of COVID-19 without reimposing national restrictions, it has become important to track the disease at a local level to identify areas in need of targeted intervention. Methods: We performed modelling on longitudinal, self-reported data from users of the COVID Symptom Study app in England betw...
Preprint
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Reports of “Long-COVID”, are rising but little is known about prevalence, risk factors, or whether it is possible to predict a protracted course early in the disease. We analysed data from 4182 incident cases of COVID-19 who logged their symptoms prospectively in the COVID Symptom Study app. 558 (13.3%) had symptoms lasting >28 days, 189 (4.5%) for...
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The maternal immune system is going through considerable changes during pregnancy. However, little is known about the determinants of the inflammatory proteome and its relation to pregnancy stages. Our aim was to investigate the plasma inflammatory proteome before, during and after pregnancy. In addition we wanted to test whether maternal and child...
Article
Objective: To test whether pregnant and non-pregnant women differ in COVID-19 symptom profile and severity. To extend previous investigations on hospitalized pregnant women to those who did not require hospitalization. Design: Observational study prospectively collecting longitudinal (smartphone application interface) and cross-sectional (web-based...
Article
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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 adu...
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Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since...
Preprint
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Background: From the beginning of COVID-19 pandemic, pregnant women have been considered at greater risk of severe morbidity and mortality. However, data on hospitalized pregnant women show that the symptom profile and risk factors for severe disease are similar to those among women who are not pregnant, although preterm birth, Cesarean delivery, a...
Preprint
Full-text available
As no one symptom can predict disease severity or the need for dedicated medical support in COVID-19, we asked if documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the CO...
Article
Objective: The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approac...
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Aims: Preventing sudden cardiac death (SCD) due to acute myocardial infarction (MI) in previously healthy patients is challenging. Proteomic analysis may lead to an understanding of biological mechanisms and provide predictive biomarkers. Methods: In this prospective, nested case-control study from northern Sweden, 87 candidate cardiovascular pr...
Article
Objective: The effect of early life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis. Research design and methods: All singleton children (n = 797,318) born in Sweden between 1 July 2005 and...
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Early life determinants of the oral microbiota have not been thoroughly elucidated. We studied the association of birth and early childhood characteristics with oral microbiota composition using 16 S ribosomal RNA (rRNA) gene sequencing in a population-based Swedish cohort of 59 children sampled at 6, 12 and 24 months of age. Repeated-measurement r...
Article
Objective: This study investigated how changes in 84 proteins over a 10-year period of aging were related to changes in measures of body fat and distribution over the same period. Methods: Cardiovascular candidate proteins were measured using the proximal extension assay technique, along with BMI and waist-hip ratio (WHR), at ages 70, 75, and 80...
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Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 c...
Article
Background and purpose: To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach. Methods: We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)...
Article
Background: Previous studies have suggested an association between season of birth and risk of childhood asthma and allergic disease. The association may be modified by birth year and region, or mediated by respiratory tract infections. Objective: We aimed to estimate the association between season of birth and risk of childhood asthma/wheeze or...
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Aims/hypothesis The pathogenesis of type 2 diabetes is not fully understood. We investigated whether circulating levels of preselected proteins were associated with the outcome ‘diabetes’ and whether these associations were causal. Methods In 2467 individuals of the population-based, cross-sectional EpiHealth study (45–75 years, 50% women), 249 pl...
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Hypertension is the leading risk factor for premature death worldwide. The identification of modifiable causes of hypertension remains an imperative task. We aimed to investigate associations between 79 proteins implicated in cardiovascular disease and longitudinal blood pressure (BP) changes in three Swedish prospective cohorts. In a discovery pha...
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Background: Dog ownership is associated with increased physical activity levels and increased social support, both of which could improve the outcome after a major cardiovascular event. Dog ownership may be particularly important in single-occupancy households where ownership provides substitutive companionship and motivation for physical activity...
Article
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Background: Newer therapeutic agents for type 2 diabetes mellitus can improve cardiovascular outcomes, but diabetes remains underdiagnosed in patients with myocardial infarction (MI). We sought to identify proteomic markers of undetected dysglycaemia (impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) to improve the identif...
Article
Background: Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons b...
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The AIRE gene plays a key role in the development of central immune tolerance by promoting thymic presentation of tissue-specific molecules. Patients with AIRE-deficiency develop multiple autoimmune manifestations and display autoantibodies against the affected tissues. In 2016 it was reported that: i) the spectrum of autoantibodies in patients wit...
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Aims We aimed to investigate whether metabolomic profiling of blood can lead to novel insights into heart failure pathogenesis or improved risk prediction. Methods and results Mass spectrometry‐based metabolomic profiling was performed in plasma or serum samples from three community‐based cohorts without heart failure at baseline (total n = 3924;...