1. |
- Lind, Lars, et al.
(author)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Journal article (peer-reviewed)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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2. |
- Bixby, H., et al.
(author)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Journal article (peer-reviewed)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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3. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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4. |
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5. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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6. |
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7. |
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8. |
- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
-
Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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9. |
- Ahdida, C., et al.
(author)
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Sensitivity of the SHiP experiment to light dark matter
- 2021
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In: Journal of High Energy Physics (JHEP). - : Springer Nature. - 1126-6708 .- 1029-8479. ; :4
-
Journal article (peer-reviewed)abstract
- Dark matter is a well-established theoretical addition to the Standard Model supported by many observations in modern astrophysics and cosmology. In this context, the existence of weakly interacting massive particles represents an appealing solution to the observed thermal relic in the Universe. Indeed, a large experimental campaign is ongoing for the detection of such particles in the sub-GeV mass range. Adopting the benchmark scenario for light dark matter particles produced in the decay of a dark photon, with αD = 0.1 and mA′ = 3mχ, we study the potential of the SHiP experiment to detect such elusive particles through its Scattering and Neutrino detector (SND). In its 5-years run, corresponding to 2 · 1020 protons on target from the CERN SPS, we find that SHiP will improve the current limits in the mass range for the dark matter from about 1 MeV to 300 MeV. In particular, we show that SHiP will probe the thermal target for Majorana candidates in most of this mass window and even reach the Pseudo-Dirac thermal relic.
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10. |
- Ahdida, C., et al.
(author)
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The SHiP experiment at the proposed CERN SPS Beam Dump Facility
- 2022
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In: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 82:5
-
Journal article (peer-reviewed)abstract
- The Search for Hidden Particles (SHiP) Collaboration has proposed a general-purpose experimental facility operating in beam-dump mode at the CERN SPS accelerator to search for light, feebly interacting particles. In the baseline configuration, the SHiP experiment incorporates two complementary detectors. The upstream detector is designed for recoil signatures of light dark matter (LDM) scattering and for neutrino physics, in particular with tau neutrinos. It consists of a spectrometer magnet housing a layered detector system with high-density LDM/neutrino target plates, emulsion-film technology and electronic high-precision tracking. The total detector target mass amounts to about eight tonnes. The downstream detector system aims at measuring visible decays of feebly interacting particles to both fully reconstructed final states and to partially reconstructed final states with neutrinos, in a nearly background-free environment. The detector consists of a 50m\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm { \,m}$$\end{document} long decay volume under vacuum followed by a spectrometer and particle identification system with a rectangular acceptance of 5 m in width and 10 m in height. Using the high-intensity beam of 400GeV\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\,\mathrm {GeV}$$\end{document} protons, the experiment aims at profiting from the 4x1019\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$4\times 10<^>{19}$$\end{document} protons per year that are currently unexploited at the SPS, over a period of 5-10 years. This allows probing dark photons, dark scalars and pseudo-scalars, and heavy neutral leptons with GeV-scale masses in the direct searches at sensitivities that largely exceed those of existing and projected experiments. The sensitivity to light dark matter through scattering reaches well below the dark matter relic density limits in the range from a few MeV/c2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathrm {\,MeV\!/}c<^>2}$$\end{document} up to 100 MeV-scale masses, and it will be possible to study tau neutrino interactions with unprecedented statistics. This paper describes the SHiP experiment baseline setup and the detector systems, together with performance results from prototypes in test beams, as it was prepared for the 2020 Update of the European Strategy for Particle Physics. The expected detector performance from simulation is summarised at the end.
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11. |
- Ahdida, C., et al.
(author)
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Track reconstruction and matching between emulsion and silicon pixel detectors for the SHiP-charm experiment
- 2022
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In: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 17:3
-
Journal article (peer-reviewed)abstract
- In July 2018 an optimization run for the proposed charm cross section measurement for SHiP was performed at the CERN SPS. A heavy, moving target instrumented with nuclear emulsion films followed by a silicon pixel tracker was installed in front of the Goliath magnet at the H4 proton beam-line. Behind the magnet, scintillating-fibre, drift-tube and RPC detectors were placed. The purpose of this run was to validate the measurement's feasibility, to develop the required analysis tools and fine-tune the detector layout. In this paper, we present the track reconstruction in the pixel tracker and the track matching with the moving emulsion detector. The pixel detector performed as expected and it is shown that, after proper alignment, a vertex matching rate of 87% is achieved.
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12. |
- Ahdida, C., et al.
(author)
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Fast simulation of muons produced at the SHiP experiment using Generative Adversarial Networks
- 2019
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 14
-
Journal article (peer-reviewed)abstract
- This paper presents a fast approach to simulating muons produced in interactions of the SPS proton beams with the target of the SHiP experiment. The SHIP experiment will be able to search for new long-lived particles produced in a 400 GeV/c SPS proton beam dump and which travel distances between fifty metres and tens of kilometers. The SHiP detector needs to operate under ultra-low background conditions and requires large simulated samples of muon induced background processes. Through the use of Generative Adversarial Networks it is possible to emulate the simulation of the interaction of 400 GeV/c proton beams with the SHiP target, an otherwise computationally intensive process. For the simulation requirements of the SHiP experiment, generative networks are capable of approximating the full simulation of the dense fixed target, offering a speed increase by a factor of O(10(6)). To evaluate the performance of such an approach, comparisons of the distributions of reconstructed muon momenta in SHiP's spectrometer between samples using the full simulation and samples produced through generative models are presented. The methods discussed in this paper can be generalised and applied to modelling any non-discrete multi-dimensional distribution.
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13. |
- Ahdida, C., et al.
(author)
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Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target
- 2020
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:3
-
Journal article (peer-reviewed)abstract
- The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27 +/- 0.07)x1011protons on target was recorded. This amounts to approximatively 1% of a SHiP spill.
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14. |
- Ahdida, C., et al.
(author)
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Sensitivity of the SHiP experiment to dark photons decaying to a pair of charged particles
- 2021
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In: European Physical Journal C. - : Springer Nature. - 1434-6044 .- 1434-6052. ; 81:5
-
Journal article (peer-reviewed)abstract
- Dark photons are hypothetical massive vector particles that could mix with ordinary photons. The simplest theoretical model is fully characterised by only two parameters: the mass of the dark photon m(gamma)D and its mixing parameter with the photon, epsilon. The sensitivity of the SHiP detector is reviewed for dark photons in the mass range between 0.002 and 10 GeV. Different productionmechanisms are simulated, with the dark photons decaying to pairs of visible fermions, including both leptons and quarks. Exclusion contours are presented and compared with those of past experiments. The SHiP detector is expected to have a unique sensitivity for m. D ranging between 0.8 and 3.3(-0.5)(+0.2) GeV, and epsilon(2) ranging between 10(-11) and 10(-17).
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15. |
- Ahdida, C., et al.
(author)
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The magnet of the scattering and neutrino detector for the SHiP experiment at CERN
- 2020
-
In: Journal of Instrumentation. - 1748-0221. ; 15:01
-
Journal article (peer-reviewed)abstract
- The Search for Hidden Particles (SHiP) experiment proposal at CERN demands a dedicated dipole magnet for its scattering and neutrino detector. This requires a very large volume to be uniformly magnetized at B > 1.2 T, with constraints regarding the inner instrumented volume as well as the external region, where no massive structures are allowed and only an extremely low stray field is admitted. In this paper we report the main technical challenges and the relevant design options providing a comprehensive design for the magnet of the SHiP Scattering and Neutrino Detector.
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16. |
- Ahdida, C., et al.
(author)
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Sensitivity of the SHiP experiment to Heavy Neutral Leptons
- 2019
-
In: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :4
-
Journal article (peer-reviewed)abstract
- Heavy Neutral Leptons (HNLs) are hypothetical particles predicted by many extensions of the Standard Model. These particles can, among other things, explain the origin of neutrino masses, generate the observed matter-antimatter asymmetry in the Universe and provide a dark matter candidate. The SHiP experiment will be able to search for HNLs produced in decays of heavy mesons and travelling distances ranging between O(50 m) and tens of kilometers before decaying. We present the sensitivity of the SHiP experiment to a number of HNL's benchmark models and provide a way to calculate the SHiP's sensitivity to HNLs for arbitrary patterns of flavour mixings. The corresponding tools and data files are also made publicly available.
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17. |
- Ahdida, C., et al.
(author)
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The experimental facility for the Search for Hidden Particles at the CERN SPS
- 2019
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In: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 14
-
Journal article (peer-reviewed)abstract
- The Search for Hidden Particles (SHiP) Collaboration has shown that the CERN SPS accelerator with its 400 GeV/c proton beam offers a unique opportunity to explore the Hidden Sector [1-3]. The proposed experiment is an intensity frontier experiment which is capable of searching for hidden particles through both visible decays and through scattering signatures from recoil of electrons or nuclei. The high-intensity experimental facility developed by the SHiP Collaboration is based on a number of key features and developments which provide the possibility of probing a large part of the parameter space for a wide range of models with light long-lived super-weakly interacting particles with masses up to O(10) GeV/c(2) in an environment of extremely clean background conditions. This paper describes the proposal for the experimental facility together with the most important feasibility studies. The paper focuses on the challenging new ideas behind the beam extraction and beam delivery, the proton beam dump, and the suppression of beam-induced background.
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18. |
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19. |
- van Rheenen, W, et al.
(author)
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Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
- 2021
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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20. |
- Nicolas, Aude, et al.
(author)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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In: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Journal article (peer-reviewed)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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21. |
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22. |
- Milstead, David A., et al.
(author)
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The active muon shield in the SHiP experiment
- 2017
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In: Journal of Instrumentation. - 1748-0221. ; 12
-
Journal article (peer-reviewed)abstract
- The SHiP experiment is designed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. An essential task for the experiment is to keep the Standard Model background level to less than 0.1 event after 2 x 10(20) protons on target. In the beam dump, around 10(11) muons will be produced per second. The muon rate in the spectrometer has to be reduced by at least four orders of magnitude to avoid muon-induced combinatorial background. A novel active muon shield is used to magnetically deflect the muons out of the acceptance of the spectrometer. This paper describes the basic principle of such a shield, its optimization and its performance.
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23. |
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24. |
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25. |
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26. |
- Foraita, R, et al.
(author)
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Does the FTO gene interact with the socioeconomic status on the obesity development among young European children? Results from the IDEFICS study.
- 2015
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39, s. 1-6
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Journal article (peer-reviewed)abstract
- Background:Various twin studies revealed that the influence of genetic factors on psychological diseases or behaviour is more expressed in socioeconomically advantaged environments. Other studies predominantly show an inverse association between socioeconomic status (SES) and childhood obesity in Western developed countries. The aim of this study is to investigate whether the fat mass and obesity-associated (FTO) gene interacts with the SES on childhood obesity in a subsample (N=4406) of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort.Methods:A structural equation model (SEM) is applied with the latent constructs obesity, dietary intakes, physical activity and fitness habits, and parental SES to estimate the main effects of the latter three variables and a FTO polymorphism on childhood obesity. Further, a multiple group SEM is used to explore whether an interaction effect exists between the single nucleotide polymorphism rs9939609 within the FTO gene and SES.Results:Significant main effects are shown for physical activity and fitness (standardised [betacrc ](s) = -0.113), SES ([betacrc ](s) = -0.057) and the FTO homozygous AA risk genotype ([betacrc ](s) = -0.177). The explained variance of obesity is ~9%. According to the multiple group approach of SEM, we see an interaction between SES and FTO with respect to their effect on childhood obesity (Δχ(2)=7.3, df=2, P=0.03).Conclusion:Children carrying the protective FTO genotype TT seem to be more protected by a favourable social environment regarding the development of obesity than children carrying the AT or AA genotype.International Journal of Obesity advance online publication, 23 September 2014; doi:10.1038/ijo.2014.156.
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27. |
- Kenna, Kevin P., et al.
(author)
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NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
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Journal article (peer-reviewed)abstract
- To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
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28. |
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29. |
- Caberlotto, L, et al.
(author)
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Cross-disease analysis of Alzheimer's disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 3965-
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Journal article (peer-reviewed)abstract
- Evidence is accumulating that the main chronic diseases of aging Alzheimer’s disease (AD) and type-2 diabetes mellitus (T2DM) share common pathophysiological mechanisms. This study aimed at applying systems biology approaches to increase the knowledge of the shared molecular pathways underpinnings of AD and T2DM. We analysed transcriptomic data of post-mortem AD and T2DM human brains to obtain disease signatures of AD and T2DM and combined them with protein-protein interaction information to construct two disease-specific networks. The overlapping AD/T2DM network proteins were then used to extract the most representative Gene Ontology biological process terms. The expression of genes identified as relevant was studied in two AD models, 3xTg-AD and ApoE3/ApoE4 targeted replacement mice. The present transcriptomic data analysis revealed a principal role for autophagy in the molecular basis of both AD and T2DM. Our experimental validation in mouse AD models confirmed the role of autophagy-related genes. Among modulated genes, Cyclin-Dependent Kinase Inhibitor 1B, Autophagy Related 16-Like 2, and insulin were highlighted. In conclusion, the present investigation revealed autophagy as the central dys-regulated pathway in highly co-morbid diseases such as AD and T2DM allowing the identification of specific genes potentially involved in disease pathophysiology which could become novel targets for therapeutic intervention.
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30. |
- Carboni, L, et al.
(author)
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Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment
- 2020
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In: Cells. - : MDPI AG. - 2073-4409. ; 9:8
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Journal article (peer-reviewed)abstract
- The Negr1 gene has been significantly associated with major depression in genetic studies. Negr1 encodes for a cell adhesion molecule cleaved by the protease Adam10, thus activating Fgfr2 and promoting neuronal spine plasticity. We investigated whether antidepressants modulate the expression of genes belonging to Negr1-Fgfr2 pathway in Flinders sensitive line (FSL) rats, in a corticosterone-treated mouse model of depression, and in mouse primary neurons. Negr1 and Adam10 were the genes mostly affected by antidepressant treatment, and in opposite directions. Negr1 was down-regulated by escitalopram in the hypothalamus of FSL rats, by fluoxetine in the hippocampal dentate gyrus of corticosterone-treated mice, and by nortriptyline in hippocampal primary neurons. Adam10 mRNA was increased by nortriptyline administration in the hypothalamus, by escitalopram in the hippocampus of FSL rats, and by fluoxetine in mouse dorsal dentate gyrus. Similarly, nortriptyline increased Adam10 expression in hippocampal cultures. Fgfr2 expression was increased by nortriptyline in the hypothalamus of FSL rats and in hippocampal neurons. Lsamp, another IgLON family protein, increased in mouse dentate gyrus after fluoxetine treatment. These findings suggest that Negr1-Fgfr2 pathway plays a role in the modulation of synaptic plasticity induced by antidepressant treatment to promote therapeutic efficacy by rearranging connectivity in corticolimbic circuits impaired in depression.
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31. |
- Coumans, J. M. J., et al.
(author)
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Emotion-driven impulsiveness but not decision-making ability and cognitive inflexibility predicts weight status in adults
- 2019
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In: Appetite. - : Elsevier BV. - 0195-6663. ; 142
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Journal article (peer-reviewed)abstract
- In this study we aimed to determine whether decision-making ability, cognitive inflexibility and emotion-driven impulsiveness are associated with weight status as expressed by body mass index (BMI), percentage body fat, waist circumference and skinfold thickness in adults from eight different European countries taking part in the I.Family study. The Bechara Gambling Task was used to assess decision-making ability (n = 1717). The Berg Card Sorting Test was used to measure cognitive inflexibility (n = 1509). Lastly, the negative urgency subscale from the UPPS-P Impulsive Behavior Scale was used to measure emotion-driven impulsiveness (n = 4450). Hierarchical regression analyses showed that more emotion-driven impulsiveness was statistically significantly associated with a higher BMI, a higher percentage body fat, and a larger waist circumference in adults, controlling for age, sex, socioeconomic status, country and binge eating; but not with skinfold thickness. Cognitive inflexibility and decision-making ability were not statistically significantly associated with any of the weight status related variables. These results support that impulsivity in response to negative emotions, but not decision-making ability or cognitive inflexibility, is associated with the susceptibility to excessive weight (as indicated by a higher BMI, a higher percentage body fat, and a larger waist circumference). In people behaving impulsively when emotional, focusing on reducing negative affect or improving coping skills is of interest in interventions targeting obesity. Clinical trial registration: The I.Family study is registered in the ISRCTN registry (ISRCTN62310987) on February 23, 2018. © 2019
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32. |
- Formisano, A., et al.
(author)
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Efficacy of neck circumference to identify metabolic syndrome in 3-10 year-old European children: Results from IDEFICS study
- 2016
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In: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 26:6, s. 510-516
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Journal article (peer-reviewed)abstract
- Background and aims: Several studies demonstrated that larger neck circumference (NC) in children and adolescents may help to identify obesity and cardio-metabolic abnormalities. We aimed to evaluate the correlation between NC and metabolic syndrome (MetS) risk factors and to determine the utility of this anthropometric index to identify MetS in European children. Methods and results: The present cross-sectional analysis includes 15,673 children (3-10 years) participating in the IDEFICS study. A continuous MetS (cMetS) score was calculated summing age and sex standardized z-scores of specific MetS risk factors. Receiver Operating Characteristic analysis, stratified by one-year age groups, was used to determine the ability of NC to identify children with unfavorable metabolic profile, corresponding to cMetS score >= 90th percentile. The areas under the curve values for NC associated with cMetS score values >= 90th percentile were significantly greater in girls than in boys (p < 0.001), except for 5 < 6 years group. For boys, optimal NC cut-off values ranged from 26.2 cm for the lowest age group (3 < 4 years), up to 30.9 cm for the highest age group (9 < 10 years). In girls, corresponding values varied from 24.9 cm to 29.6 cm. Conclusion: The study demonstrated the efficacy of NC in identifying European children with an unfavorable metabolic profile.
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33. |
- Haerens, L, et al.
(author)
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Formative research to develop the IDEFICS physical activity intervention component: findings from focus groups with children and parents
- 2010
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In: Journal of Physical Activity and Health. - Champaign, IL : HUMAN KINETICS PUBL INC. - 1543-3080 .- 1543-5474. ; 7:2, s. 246-256
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Journal article (peer-reviewed)abstract
- BACKGROUND: The current study aimed at describing influencing factors for physical activity among young children to determine the best approaches for developing the IDEFICS community based intervention. METHODS: In 8 European sites a trained moderator conducted a minimum of 4 focus groups using standardized questioning guides. A total of 56 focus groups were conducted including 36 focus groups with parents and 20 focus groups with children, of which 74 were boys and 81 girls. Key findings were identified through independent reviews of focus group summary reports using content analysis methods. FINDINGS: Findings were generally consistent across countries. The greatest emphasis was on environmental physical (eg, seasonal influences, availability of facilities and safety), institutional (eg, length of breaks at school), and social factors (eg, role modeling of parents). Most cited personal factors by parents were age, social economical status, and perceived barriers. Both children and parents mentioned the importance of children's preferences. CONCLUSIONS: To increase physical activity levels of young children the intervention should aim at creating an environment (physical, institutional, social) supportive of physical activity. On the other hand strategies should take into account personal factors like age and social economical status and should consider personal barriers too.
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34. |
- Lauria, F., et al.
(author)
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A common variant and the transcript levels of MC4R gene are associated with adiposity in children: The IDEFICS study
- 2016
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 101:11, s. 4229-4236
-
Journal article (peer-reviewed)abstract
- Context: The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake. Objectives: The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children. Design: The Identification and Prevention of Dietary-and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1). Setting and Participants: A total of 16 228 schoolchildren (2-9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses. Main Outcome Measures: Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively. Results: At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P<.001).Noassociation was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P ≤ .05) but were not influenced by variants rs17782313 and rs17700633. Conclusions: The common variant rs17782313 near MC4R was cross-sectionally and longitudinally associated with body mass index and measures of body fatness in children aged 2-9 years. We showed, for the first time in humans, that MC4R expression levels in PBCs are related to body fat distribution and percentage of energy intake from carbohydrates and fat. (J Clin Endocrinol Metab 101: 4229-4236, 2016). Copyright © 2016 by the Endocrine Society.
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35. |
- Lauria, F., et al.
(author)
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Ultra-processed foods consumption and diet quality of European children, adolescents and adults: Results from the I.Family study
- 2021
-
In: Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 31:11, s. 3031-3043
-
Journal article (peer-reviewed)abstract
- Background and aims: Food processing has been indicated as a factor capable of negatively affecting the global food system, including the profile of consumers' diets. The objectives of the present study were to provide a description of the consumption of ultra-processed foods (UPFs) in the large population of children, adolescents and adults from eight European countries participating to the I.Family study, and to investigate the association between UPFs intake and nutritional quality of the diet. Methods and results: Dietary intake was assessed using a 24-h dietary recall. The quality of the diet was evaluated by the Healthy Dietary Adherence Score (HDAS) using an FFQ. UPFs were classified according to the NOVA classification. Almost half of the daily energy intake of the 7073 participants came from UPFs, and this trend decreased progressively with age. UPFs contributed more than 50 % of the daily intake of total and saturated fat, carbohydrates and about 70 % of sugars intake in children and adolescents. No differences in UPFs consumption were found according to the educational and socio-economic status of the population. Energy intake increased across the quintiles of UPFs intake, while HDAS decreased. The frequency of consumption of fruit and vegetable, fish, and fibre rich foods was low in the fifth quintile of UPFs intake, both in adolescents and in adults. The consumption of foods rich in calories and low in nutritional content, operationally defined as "junk food", was significantly higher in the fifth quintile. Conclusions: In the population of the European I.Family study, UPFs contributed a large proportion of the daily energy intake, especially in children and adolescents. Higher consumption of UPFs was associated with a lower quality of the diet. Registration number for clinical trials: ISRCTN62310987. 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
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36. |
- Santaliestra-Pasias, A. M., et al.
(author)
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Food and beverage intakes according to physical activity levels in European children: the IDEFICS (Identification and prevention of Dietary and lifestyle induced health EFfects In Children and infantS) study
- 2018
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In: Public Health Nutrition. - : Cambridge University Press (CUP). - 1368-9800 .- 1475-2727. ; 21:9, s. 1717-1725
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Journal article (peer-reviewed)abstract
- Objective: Physical activity (PA) levels and dietary habits are considered some of the most important factors associated with obesity. The present study aimed to examine the association between PA level and food and beverage consumption in European children (2-10 years old). Design/Setting/Subjects: A sample of 7229 children (49.0% girls) from eight European countries participating in the IDEFICS (Identification and prevention of Dietary and lifestyle induced health EFfects In Children and infantS) study was included. Moderate-to-vigorous PA (MVPA) was assessed objectively with accelerometers. FFQ was used to register dietary habits. ANCOVA and binary logistic regression were applied. Results: Boys who spent less time in MVPA reported lower consumption of vegetables, fruits, cereals, yoghurt, milk, bread, pasta, candies and sugar-sweetened beverages (SSB) than boys who spent more time in MVPA (P < 0.05). Moreover, boys who spent less time in MVPA were more likely to consume fast foods and water than those in the highest MVPA tertile (P < 0.05). Girls who spent less time in MVPA reported lower consumption frequencies of vegetables, pasta, bread, yoghurt, candies, jam/honey and SSB than girls in the highest MVPA tertile (P < 0.05). Also, girls in the lowest MVPA tertile were more likely to consume fast foods and water than those with high levels of MVPA (P < 0.05). Conclusions: Food intake among European children varied with different levels of daily MVPA. Low time spent in MVPA was associated with lowest consumption of both high-and low-energy-dense foods and high fast-food consumption.
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37. |
- Santaliestra-Pasías, A. M., et al.
(author)
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Prospective physical fitness status and development of cardiometabolic risk in children according to body fat and lifestyle behaviours: The IDEFICS study
- 2021
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In: Pediatric Obesity. - : Wiley. - 2047-6302 .- 2047-6310. ; 16:11
-
Journal article (peer-reviewed)abstract
- Background: Elevated cardiometabolic risk (CMR) is an important factor for cardiovascular diseases later in life while physical fitness seems to decrease CMR. Objective: Thus, the aim of the present study is to assess the association between muscular fitness (MF) and cardiorespiratory fitness (CRF) on CMR in European children, both cross-sectional and longitudinally. Methods: A total of 289 children (49.5% males) from eight European countries, aged 6 to 9, with longitudinal information on blood pressure, triglycerides, total cholesterol, HDL-cholesterol, homoeostasis model assessment, body mass index, data on fitness level, objectively measured physical activity (PA), diet quality, and total screen time were included. A CMR score was calculated and dichotomized. MF and CRF were also dichotomized. Cross-sectional and longitudinal multilevel logistic regressions adjusting for lifestyle behaviours were performed. Results: Reaching a high level of MF during childhood as well as remaining in that level over-time were associated with an 82% and 62% lower probability of high CMR at follow-up, respectively. Also, children who became top CRF over time, showed a 77% lower probability (P < 0.05) of being in the highest CMR quartile at follow-up, independently of sociodemographic and lifestyle indicators. Conclusions: A high MF at early childhood and during childhood reduces the odds of having CMR. Same occurs with the improvement of CRF during childhood. These findings highlight the importance of enhancing fitness to avoid CMR already in children. © 2021 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.
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38. |
- Stahlmann, Katharina, et al.
(author)
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Family structure in relation to body mass index and metabolic score in European children and adolescents
- 2022
-
In: Pediatric Obesity. - : Wiley. - 2047-6310 .- 2047-6302. ; 17:12
-
Journal article (peer-reviewed)abstract
- Background Living in single parent and blended families or as an only child-compared to living in two-parent biological families or with siblings, respectively-is associated with a higher body mass index (BMI) in cross-sectional studies. However, longitudinal research addressing the children's BMI in this context is scarce. Further, little is known about the association between family structure and metabolic health. Objectives This study aimed at investigating the association between both aspects of family structure with BMI and a metabolic score (MetS). Methods Cross-sectional data from 7804 children participating in the European multi-center I.Family study (2013/2014) and longitudinal data from 5621 children who also participated previously in the IDEFICS study (2007-2010) were used. Family structure was assessed by a detailed interview. BMI z-score and the MetS were based on measured anthropometry, blood pressure, high-density lipoprotein, blood glucose, and triglycerides. Linear regressions were performed to model associations between family structure with BMI and MetS. Results Children from single-parent families had higher BMI z-scores in the cross-sectional (beta = 0.09, 95% confidence interval [CI]: 0.001 to 0.18) and longitudinal analyses compared to those from two-parent families. Cross-sectionally, the number of siblings was associated with lower BMI z-scores (beta = -0.07, 95% CI: -0.10 to -0.03) and lower MetS (beta = -0.14, 95% CI: -0.26 to -0.01). Longitudinally, only children between baseline and follow-up had higher BMI z-scores at follow-up (beta = 0.07, 95% CI: 0.01 to 0.14) compared to stable siblings. Conclusion Obesity prevention measures should focus on single-parent households and families with an only child.
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39. |
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40. |
- Fridolfsson, Jonatan, 1992, et al.
(author)
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High-intensity activity is more strongly associated with metabolic health in children compared to sedentary time: a cross-sectional study of the I.Family cohort
- 2021
-
In: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 18:1
-
Journal article (peer-reviewed)abstract
- Background Physical activity (PA) during childhood is important for preventing future metabolic syndrome (MetS). To examine the relationship between PA and MetS in more detail, accurate measures of PA are needed. Previous studies have only utilized a small part of the information available from accelerometer measured PA. This study investigated the association between measured PA and MetS in children with a new method for data processing and analyses that enable more detailed interpretation of PA intensity level. Methods The association between PA pattern and risk factors related to MetS was investigated in a cross- sectional sample of children (n = 2592, mean age 10.9 years, 49.4% male) participating in the European multicenter I. Family study. The risk factors examined include body mass index, blood pressure, high-density lipoprotein cholesterol, insulin resistance and a combined risk factor score (MetS score). PA was measured by triaxial accelerometers and raw data was processed using the 10 Hz frequency extended method (FEM). The PA output was divided into an intensity spectrum and the association with MetS risk factors was analyzed by partial least squares regression. Results PA patterns differed between the European countries investigated, with Swedish children being most active and Italian children least active. Moderate intensity physical activity was associated with lower insulin resistance (R-2 = 2.8%), while vigorous intensity physical activity was associated with lower body mass index (R-2 = 3.6%), MetS score (R-2 = 3.1%) and higher high-density lipoprotein cholesterol (R-2 = 2.3%). PA of all intensities was associated with lower systolic- and diastolic blood pressure, although the associations were weaker than for the other risk factors (R-2 = 1.5% and R-2 = 1.4%). However, the multivariate analysis implies that the entire PA pattern must be considered. The main difference in PA was observed between normal weight and overweight children. Conclusions The present study suggests a greater importance of more PA corresponding to an intensity of at least brisk walking with inclusion of high-intense exercise, rather than a limited time spent sedentary, in the association to metabolic health in children. The methods of data processing and statistical analysis enabled accurate analysis and interpretation of the health benefits of high intensity PA that have not been shown previously.
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41. |
- Gwozdz, W., et al.
(author)
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Maternal employment and childhood obesity - A European perspective
- 2013
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In: Journal of Health Economics. - : Elsevier BV. - 0167-6296 .- 1879-1646. ; 32:4, s. 728-742
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Journal article (peer-reviewed)abstract
- The substantial increase in female employment rates in Europe over the past two decades has often been linked in political and public rhetoric to negative effects on child development, including obesity. We analyse this association between maternal employment and childhood obesity using rich objective reports of various anthropometric and other measures of fatness from the IDEFICS study of children aged 2-9 in 16 regions of eight European countries. Based on such data as accelerometer measures and information from nutritional diaries, we also investigate the effects of maternal employment on obesity's main drivers: calorie intake and physical activity. Our analysis provides little evidence for any association between maternal employment and childhood obesity, diet or physical activity. (c) 2013 Elsevier B.V. All rights reserved.
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42. |
- Gwozdz, W., et al.
(author)
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Peer effects on obesity in a sample of European children
- 2015
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In: Economics & Human Biology. - : Elsevier BV. - 1570-677X .- 1873-6130. ; 18, s. 139-152
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Journal article (peer-reviewed)abstract
- This study analyzes peer effects on childhood obesity using data from the first two waves of the IDEFICS study, which applies several anthropometric and other measures of fatness to approximately 14,000 children aged two to nine participating in both waves in 16 regions of eight European countries. Peers are defined as same-sex children in the same school and age group. The results show that peer effects do exist in this European sample but that they differ among both regions and different fatness measures. Peer effects are larger in Spain, Italy, and Cyprus - the more collectivist regions in our sample - while waist circumference generally gives rise to larger peer effects than BMI. We also provide evidence that parental misperceptions of their own children's weight goes hand in hand With fatter peer groups, supporting the notion that in making such assessments, parents compare their children's weight with that of friends and schoolmates.
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43. |
- Gwozdz, W., et al.
(author)
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Peer Effects on Weight Status, Dietary Behaviour and Physical Activity among Adolescents in Europe: Findings from the I.Family Study
- 2019
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In: Kyklos. - : Wiley. - 0023-5962 .- 1467-6435. ; 72:2, s. 270-296
-
Journal article (peer-reviewed)abstract
- This study uses survey data from the I. Family Study to investigate the association between adolescent and peer overweight in a sample of adolescents aged 12-16 from six European countries. We find clear evidence of peer effects on body mass index, waist circumference, and body fat, which are stronger among adolescents at the upper end of overweight distribution. We also provide evidence that both consumption of less healthy foods and time spent in leisure time physical activity and audio-visual media are positively associated with similar behaviours among friends. These observations may suggest that peer effects on adolescent overweight operate by influencing friends' behaviour patterns, especially unhealthy food consumption and physical in) activity.
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44. |
- Haque, Faiz, et al.
(author)
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Per- and polyfluoroalkyl substances (PFAS) in white-tailed sea eagle eggs from Sweden: Temporal trends (1969-2021), spatial variations, fluorine mass balance, and suspect screening
- 2023
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In: Environmental Science. - 2050-7887 .- 2050-7895.
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Journal article (peer-reviewed)abstract
- Temporal and spatial trends of 15 per- and polyfluoroalkyl substances (PFAS) were determined in white-tailed sea eagle (WTSE) eggs (Haliaeetus albicilla) from two inland and two coastal regions of Sweden between 1969 and 2021. PFAS concentrations generally increased from ∼1969 to ∼1990s–2010 (depending on target and site) and thereafter plateaued or declined, with perfluorooctane sulfonamide (FOSA) and perfluorooctane sulfonate (PFOS) declining faster than most perfluoroalkyl carboxylic acids (PFCAs). The net result was a shift in the PFAS profile from PFOS-dominant in 1969–2010 to an increased prevalence of PFCAs over the last decade. Further, during the entire period higher PFAS concentrations were generally observed in coastal populations, possibly due to differences in diet and/or proximity to more densely populated areas. Fluorine mass balance determination in pooled samples from three of the regions (2019–2021) indicated that target PFAS accounted for the vast majority (i.e. 81–100%) of extractable organic fluorine (EOF). Nevertheless, high resolution mass-spectrometry-based suspect screening identified 55 suspects (31 at a confidence level [CL] of 1–3 and 24 at a CL of 4–5), of which 43 were substances not included in the targeted analysis. Semi-quantification of CL ≤ 2 suspects increased the identified EOF to >90% in coastal samples. In addition to showing the impact of PFAS regulation and phase-out initiatives, this study demonstrates that most extractable organofluorine in WTSE eggs is made up of known (legacy) PFAS, albeit with low levels of novel substances.
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45. |
- Herrmann, D, et al.
(author)
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Reference values of bone stiffness index and C-terminal telopeptide in healthy European children.
- 2014
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In: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 38 Suppl 2
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Journal article (peer-reviewed)abstract
- Quantitative ultrasound measurements and bone metabolic markers can help to monitor bone health and to detect impaired skeletal development. Population-based reference values for children may serve as a basis for preventive measures to reduce the risk of osteoporosis and osteoporotic fractures in later life. This is the first paper providing age-, sex- and height-specific reference values for bone stiffness index (SI) and serum carboxy-terminal cross-linking telopeptide of type I collagen (CTX) in healthy, apparently prepubertal children.
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46. |
- Iacomino, G., et al.
(author)
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Circulating microRNAs are associated with early childhood obesity: results of the I.Family Study
- 2019
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In: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 14
-
Journal article (peer-reviewed)abstract
- BackgroundNearly 10years ago, the World Health Organization reported the increasing prevalence of overweight and obesity worldwide as a challenge for public health due to the associated adverse consequences. Epidemiological studies established a firm relationship between an elevated body mass index and chronic conditions such as diabetes, dyslipidemia, hypertension, heart disease, non-alcoholic fatty liver disease, and some types of cancer. Omic studies demonstrated that microRNA (miRNA) profile changes in tissues correlate with a number of diseases, including obesity. Recent studies showed a remarkable stability of miRNAs also in blood, emphasizing their potential as theranostic agents for a variety of disorders and conditions. A number of miRNAs enriched in homeostasis of obesity and metabolic disorders have been characterized in previous researches.AimThis work was finalized to investigate the differential circulating miRNAs signature in early childhood obesity. Our cross-sectional study analyzed the signature of circulating miRNAs in plasma samples of normal weight (n=159) and overweight/obese (n=149) children and adolescents participating to the I.Family study, an EC-funded study finalized to investigate the etiology of overweight, obesity and related disorders and the determinants of food choice, lifestyle, and related health outcomes in children and adolescents of eight European countries (www.ifamilystudy.eu).ResultsDifferences in miRNA signature with respect to anthropometric and biochemical variables were analyzed. A high degree of variability in levels of circulating miRNAs was identified among children from different countries, in line with recent reports supporting the hypothesis that these molecules are likewise affected by environmental and lifestyle factors. A panel of miRNAs differentially expressed in overweight/low-grade obesity children was characterized (miR-551a and miR-501-5p resulted upregulated; miR-10b-5p, miR-191-3p, miR-215-5p, and miR-874-3p resulted downregulated). ROC curves were also constructed for experimentally confirmed miRNAs. Single miRNAs generally exhibited low AUC values with the highest values for miR-874-3p and miR-501-5p which in combination provided an interesting value (AUC=0.782). Pearson's analysis confirmed that miR-10b-5p, miR-215-5p, miR-501-5p, miR-551a, and miR-874-3p significantly correlated with BMI z-score. Molecular interactions of obesity-associated miRNAs were also predicted by bioinformatics tools.ConclusionsOur work showed that several circulating miRNAs are differentially represented in overweight/low-grade obesity children and adolescents. Although causal pathways cannot be firmly inferred, it is conceivable that circulating miRNAs may be new biomarkers of early childhood obesity.Trial registrationISRCTN, ISRCTN62310987. Registered 23/02/2018 - Retrospectively registered.
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47. |
- Iacomino, G., et al.
(author)
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Circulating miRNAs are associated with sleep duration in children/adolescents: Results of the I.Family Study
- 2020
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In: Experimental Physiology. - : Wiley. - 0958-0670 .- 1469-445X. ; 105:2, s. 347-356
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Journal article (peer-reviewed)abstract
- New Findings What is the central question of this study?Are differential patterns of circulating miRNAs associated with sleep duration in normal-weight European children and adolescents? What is the main finding and its importance?Differences in the expression level of circulating miR-26b-3p and miR-485-5p are positively associated with total sleep duration in healthy normal-weight children and adolescents. It is commonly recognized that sleep is essential for children's health, and that insufficient sleep duration is associated with negative health outcomes. In humans, sleep duration and quality are influenced by genetic, environmental and social factors. Epigenetic mechanisms, likewise, regulate circadian rhythms and sleep patterns. In the present study, we aimed to identify circulating microRNAs associated with sleep duration in a subsample of normal-weight European children/adolescents (n = 111) participating in the I.Family Study. Subjects were divided into two groups based upon self-reported sleep duration, according to the recommended amount of sleep for paediatric populations. Sleep needs for children <13 years were at least 9 h per day, and for children >13 were at least 8 h per day. There were group differences (short sleepers versus normal sleepers) in circulating levels of miR-26b-3p (mean (95% CI) = 2.0 (1.3-2.7) versus 2.3 (1.9-2.7), P = 0.05) and miR-485-5p (mean (95% CI) = 0.6 (0.3-0.9) versus 0.9 (0.7 - 1.0), P < 0.001), adjusting for country of origin, age, sex, pubertal status, screen time and highest educational level of parents. Our findings show for the first time that sleep duration reflects the profile of specific circulating microRNAs in school-aged children and adolescents. It is conceivable that epigenetic modifications, mainly related to circadian rhythm control, may be modulated or interfere with sleep duration.
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48. |
- Iacomino, G., et al.
(author)
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The association of circulating miR-191 and miR-375 expression levels with markers of insulin resistance in overweight children: an exploratory analysis of the I.Family Study
- 2021
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In: Genes and Nutrition. - : Springer Science and Business Media LLC. - 1555-8932 .- 1865-3499. ; 16:1
-
Journal article (peer-reviewed)abstract
- Background: In recent years, the exciting emergence of circulating miRNAs as stable, reproducible, and consistent among individuals has opened a promising research opportunity for the detection of non-invasive biomarkers. A firm connection has been established between circulating miRNAs and glycaemic as well as metabolic homeostasis, showing that levels of specific miRNAs vary under different physio-pathological conditions. Objective: In this pilot study, we investigated the expression of candidate miRNAs, hsa-miR-191-3p and hsa-miR-375, in relation to biomarkers associated with insulin sensitivity in a subgroup (n=58) of subjects participating to the European I.Family Study, a project aimed to assess the determinants of eating behaviour in children and adolescents and related health outcomes. The sample included overweight/obese children/adolescents since overweight/obesity is a known risk factor for impaired glucose homeostasis and metabolic disorders. Biological targets of candidate miRNAs were also explored in silico. Results: We observed a significant association of the two miRNAs and early changes in glycaemic homeostasis, independent of covariates including country of origin, age, BMI z-score, puberty status, highest educational level of parents, total energy intake, energy from fats, energy from carbohydrates, and energy from proteins. Conclusion: Identification of circulating miRNAs associated with insulin impairment may offer novel approaches of assessing early variations in insulin sensitivity and provide evidence about the molecular mechanisms connected to early changes in glycaemic homeostasis. Trial registration: ISRCTN, ISRCTN62310987. Retrospectively registered, http://isrctn.com/ISRCTN62310987 © 2021, The Author(s).
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49. |
- Langeheine, M., et al.
(author)
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Attrition in the European Child Cohort IDEFICS/I. Family: Exploring Associations Between Attrition and Body Mass Index
- 2018
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In: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 6
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Journal article (peer-reviewed)abstract
- Attrition may lead to bias in epidemiological cohorts, since participants who are healthier and have a higher social position are less likely to drop out. We investigated possible selection effects regarding key exposures and outcomes in the IDEFICS/I. Family study, a large European cohort on the etiology of overweight, obesity and related disorders during childhood and adulthood. We applied multilevel logistic regression to investigate associations of attrition with sociodemographic variables, weight status, and study compliance and assessed attrition across time regarding children's weight status and variations of attrition across participating countries. We investigated selection effects with regard to social position, adherence to key messages concerning a healthy lifestyle, and children's weight status. Attrition was associated with a higher weight status of children, lower children's study compliance, older age, lower parental education, and parent's migration background, consistent across time and participating countries. Although overweight (odds ratio 1.17, 99% confidence interval 1.05-1.29) or obese children (odds ratio 1.18, 99% confidence interval 1.03-1.36) were more prone to drop-out, attrition only seemed to slightly distort the distribution of children's BMI at the upper tail. Restricting the sample to subgroups with different attrition characteristics only marginally affected exposure-outcome associations. Our results suggest that IDEFICS/I. Family provides valid estimates of relations between socio-economic position, health-related behaviors, and weight status.
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50. |
- Lauria, F., et al.
(author)
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Circulating miRNAs Are Associated with Inflammation Biomarkers in Children with Overweight and Obesity: Results of the I.Family Study
- 2022
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In: Genes. - : MDPI AG. - 2073-4425. ; 13:4
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Journal article (peer-reviewed)abstract
- Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity, and inflammation. In this study, we aimed at identifying the involvement of candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-alpha, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity.
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