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  • Munn-Chernoff, M. A., et al. (författare)
  • Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
  • 2021
  • Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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  • Silventoinen, K., et al. (författare)
  • The CODATwins Project : The current status and recent findings of COllaborative Project of Development of Anthropometrical Measures in Twins
  • 2019
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 800-808
  • Tidskriftsartikel (refereegranskat)abstract
    • The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status. 
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  • Ip, H. F., et al. (författare)
  • Genetic association study of childhood aggression across raters, instruments, and age
  • 2021
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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  • Jelenkovic, A., et al. (författare)
  • Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994
  • 2016
  • Ingår i: eLIFE. - Cambridge, United Kingdom : eLife Sciences Publications. - 2050-084X. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.
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  • Silventoinen, K., et al. (författare)
  • Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts
  • 2017
  • Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 106:2, s. 457-466
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood.Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity.Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs).Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI.Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.
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  • Anderson, Cynthia M., et al. (författare)
  • Permanent Genetic Resources added to Molecular Ecology Resources Database 1 December 2009-31 January 2010
  • 2010
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:3, s. 576-579
  • Tidskriftsartikel (refereegranskat)abstract
    • This article documents the addition of 220 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Allanblackia floribunda, Amblyraja radiata, Bactrocera cucurbitae, Brachycaudus helichrysi, Calopogonium mucunoides, Dissodactylus primitivus, Elodea canadensis, Ephydatia fluviatilis, Galapaganus howdenae howdenae, Hoplostethus atlanticus, Ischnura elegans, Larimichthys polyactis, Opheodrys vernalis, Pelteobagrus fulvidraco, Phragmidium violaceum, Pistacia vera, and Thunnus thynnus. These loci were cross-tested on the following species: Allanblackia gabonensis, Allanblackia stanerana, Neoceratitis cyanescens, Dacus ciliatus, Dacus demmerezi, Bactrocera zonata, Ceratitis capitata, Ceratitis rosa, Ceratits catoirii, Dacus punctatifrons, Ephydatia mulleri, Spongilla lacustris, Geodia cydonium, Axinella sp., Ischnura graellsii, Ischnura ramburii, Ischnura pumilio, Pistacia integerrima and Pistacia terebinthus.
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  • Jelenkovic, Aline, et al. (författare)
  • Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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  • Silventoinen, Karri, et al. (författare)
  • The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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  • Silventoinen, Karri, et al. (författare)
  • Education in twins and their parents across birth cohorts over 100 years : an individual-level pooled analysis of 42 twin cohorts
  • 2017
  • Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
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  • Solmi, M, et al. (författare)
  • 2022
  • Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)
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  • Silventoinen, K., et al. (författare)
  • Educational attainment of same-sex and opposite-sex dizygotic twins : An individual-level pooled study of 19 twin cohorts
  • 2021
  • Ingår i: Hormones and Behavior. - : Elsevier. - 0018-506X .- 1095-6867. ; 136
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers.
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  • Piirtola, M., et al. (författare)
  • Association of current and former smoking with body mass index : A study of smoking discordant twin pairs from 21 twin cohorts
  • 2018
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Smokers tend to weigh less than never smokers, while successful quitting leads to an increase in body weight. Because smokers and non-smokers may differ in genetic and environmental family background, we analysed data from twin pairs in which the co-twins differed by their smoking behaviour to evaluate if the association between smoking and body mass index (BMI) remains after controlling for family background.Methods and findings The international CODATwins database includes information on smoking and BMI measured between 1960 and 2012 from 156,593 twin individuals 18–69 years of age. Individual-based data (230,378 measurements) and data of smoking discordant twin pairs (altogether 30,014 pairwise measurements, 36% from monozygotic [MZ] pairs) were analysed with linear fixed-effects regression models by 10-year periods. In MZ pairs, the smoking co-twin had, on average, 0.57 kg/m2 lower BMI in men (95% confidence interval (CI): 0.49, 0.70) and 0.65 kg/m2 lower BMI in women (95% CI: 0.52, 0.79) than the never smoking co-twin. Former smokers had 0.70 kg/m2 higher BMI among men (95% CI: 0.63, 0.78) and 0.62 kg/ m2 higher BMI among women (95% CI: 0.51, 0.73) than their currently smoking MZ co-twins. Little difference in BMI was observed when comparing former smoking co-twins with their never smoking MZ co-twins (0.13 kg/m2, 95% CI 0.04, 0.23 among men; -0.04 kg/m2, 95% CI -0.16, 0.09 among women). The associations were similar within dizygotic pairs and when analysing twins as individuals. The observed series of cross-sectional associations were independent of sex, age, and measurement decade.ConclusionsSmoking is associated with lower BMI and smoking cessation with higher BMI. However, the net effect of smoking and subsequent cessation on weight development appears to be minimal, i.e. never more than an average of 0.7 kg/m2 
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  • Jami, E. S., et al. (författare)
  • Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
  • 2022
  • Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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  • Maier, O., et al. (författare)
  • ISLES 2015-A public evaluation benchmark for ischemic stroke lesion segmentation from multispectral MRI
  • 2017
  • Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415 .- 1361-8423. ; 35, s. 250-269
  • Tidskriftsartikel (refereegranskat)abstract
    • Ischemic stroke is the most common cerebrovascular disease, and its diagnosis, treatment, and study relies on non-invasive imaging. Algorithms for stroke lesion segmentation from magnetic resonance imaging (MRI) volumes are intensely researched, but the reported results are largely incomparable due to different datasets and evaluation schemes. We approached this urgent problem of comparability with the Ischemic Stroke Lesion Segmentation (ISLES) challenge organized in conjunction with the MICCAI 2015 conference. In this paper we propose a common evaluation framework, describe the publicly available datasets, and present the results of the two sub-challenges: Sub-Acute Stroke Lesion Segmentation (SISS) and Stroke Perfusion Estimation (SPES). A total of 16 research groups participated with a wide range of state-of-the-art automatic segmentation algorithms. A thorough analysis of the obtained data enables a critical evaluation of the current state-of-the-art, recommendations for further developments, and the identification of remaining challenges. The segmentation of acute perfusion lesions addressed in SPES was found to be feasible. However, algorithms applied to sub-acute lesion segmentation in SISS still lack accuracy. Overall, no algorithmic characteristic of any method was found to perform superior to the others. Instead, the characteristics of stroke lesion appearances, their evolution, and the observed challenges should be studied in detail. The annotated ISLES image datasets continue to be publicly available through an online evaluation system to serve as an ongoing benchmarking resource (www.isles-challenge.org).
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  • Silventoinen, Karri, et al. (författare)
  • Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
  • 2020
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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24.
  • Brevini, T, et al. (författare)
  • FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
  • Tidskriftsartikel (refereegranskat)abstract
    • Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
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  • Silventoinen, Karri, et al. (författare)
  • Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts
  • 2022
  • Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
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  • Abudurexiti, A, et al. (författare)
  • Taxonomy of the order Bunyavirales: update 2019
  • 2019
  • Ingår i: Archives of virology. - : Springer Science and Business Media LLC. - 1432-8798 .- 0304-8608. ; 164:7, s. 1949-1965
  • Tidskriftsartikel (refereegranskat)
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31.
  • Cook, TL, et al. (författare)
  • Psychosocial determinants and perceived environmental barriers as mediators of the effectiveness of a web-based tailored intervention promoting physical activity in adolescents: the HELENA Activ-O-Meter
  • 2014
  • Ingår i: Journal of physical activity & health. - : Human Kinetics. - 1543-5474 .- 1543-3080. ; 11:4, s. 741-751
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to examine if psychosocial determinants (attitudes, self-efficacy, social support from a sports partner) and perceived environmental barriers (PEB) of physical activity (PA) mediated the effect of a 3-month Internet-based intervention on PA in European adolescents.Methods:A sample of 536 adolescents (51% boys) aged 12–17 years were randomly assigned to intervention or control condition. Questionnaires were used to assess different PA behaviors, psychosocial determinants and PEB at baseline and at 3-month follow-up. Mediating effects were assessed with the bootstrapping method.Results:PEB regarding neighborhood safety mediated the effect of the intervention on all PA indices. PEB regarding sports facilities availability at neighborhood and PEB regarding sport-related facilities availability at school mediated the effect of the intervention on moderate to vigorous PA (MVPA) and moderate PA (in leisure time and at school, respectively). Social support from a sports partner suppressed the effect of the intervention on vigorous PA and MVPA. No other factor had a mediation effect.Conclusions:All PEB measures appear to mediate PA behaviors of different intensities and in different contexts. Interventions promoting PA in adolescents should also focus on improving the targeted PEB as mediators of engagement in PA to bring the desired effects in actual behaviors.
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32.
  • Danilovich, T., et al. (författare)
  • ATOMIUM: halide molecules around the S-type AGB star W Aquilae
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 655
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. S-type asymptotic giant branch (AGB) stars are thought to be intermediates in the evolution of oxygen- to carbon-rich AGB stars. The chemical compositions of their circumstellar envelopes are also intermediate but have not been studied in as much detail as their carbon- and oxygen-rich counterparts. W Aql is a nearby S-type star, with well-known circumstellar parameters, making it an ideal object for in-depth study of less common molecules. Aims. We aim to determine the abundances of AlCl and AlF from rotational lines, which have been observed for the first time towards an S-type AGB star. In combination with models based on PACS observations, we aim to update our chemical kinetics network based on these results. Methods. We analyse ALMA observations towards W Aql of AlCl in the ground and first two vibrationally excited states and AlF in the ground vibrational state. Using radiative transfer models, we determine the abundances and spatial abundance distributions of (AlCl)-Cl-35, (AlCl)-Cl-37, and AlF. We also model HCl and HF emission and compare these models to PACS spectra to constrain the abundances of these species. Results. AlCl is found in clumps very close to the star, with emission confined within 0 ''.1 of the star. AlF emission is more extended, with faint emission extending 0 ''.2 to 0 ''.6 from the continuum peak. We find peak abundances, relative to H-2, of 1.7 x 10(-7) for (AlCl)-Cl-35, 7 x 10(-8) for (AlCl)-Cl-37, and 1 x 10(-7) for AlF. From the PACS spectra, we find abundances of 9.7 x 10(-8) and <= 10(-8), relative to H-2, for HCl and HF, respectively. Conclusions. The AlF abundance exceeds the solar F abundance, indicating that fluorine synthesised in the AGB star has already been dredged up to the surface of the star and ejected into the circumstellar envelope. From our analysis of chemical reactions in the wind, we conclude that AlF may participate in the dust formation process, but we cannot fully explain the rapid depletion of AlCl seen in the wind.
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33.
  • Furberg, Helena, et al. (författare)
  • Genome-wide meta-analyses identify multiple loci associated with smoking behavior
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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34.
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35.
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36.
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37.
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38.
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39.
  • Verbestel, V., et al. (författare)
  • Effectiveness of the IDEFICS intervention on objectively measured physical activity and sedentary time in European children
  • 2015
  • Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:Suppl. 2, s. 57-67
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThis paper reports on the effectiveness of the prevention of dietary- and lifestyle-induced health effects in children and infants (IDEFICS) intervention on objectively measured physical activity (PA) and sedentary time (ST) in 2- to 9.9-year-old European boys and girls. MethodsThe intervention was evaluated after 2years through a non-randomized cluster-controlled trial in eight European countries (one control and one intervention community per country). All children in the intervention group received a culturally adapted childhood obesity prevention programme through the community, schools/kindergartens and family. A random sub-sample of children participating in the IDEFICS study wore an accelerometer at baseline and follow-up for at least 3days (n=9,184). Of this sample, 81% provided valid accelerometer data at baseline (n=7,413; 51% boys; 6.211.76years; boys: 617170cpmday(-1); girls 556 +/- 156cpmday(-1)) and 3,010 children provided valid accelerometer data at baseline and during the follow-up survey 2years later. ResultsIn boys and girls, no significant differences in PA and ST were found between intervention and control groups over 2years. Strong temporal effects were found in the total sample of boys and girls: the percentage of time spent in light PA per day decreased by 4 percentage points in both boys and girls between baseline and follow-up (both: p<0.001), while time spent in ST per day increased by 4 percentage points in both sexes over time (both: p<0.001). Percentage of time spent in moderate-to-vigorous PA per day remained stable over time in boys and girls. ConclusionDespite the socio-ecological approach and implementation of a culturally adapted intervention in each country, no effects of the IDEFICS intervention were found on children's objectively measured PA and ST. Behavioural interventions for children may need to enhance specificity and intensity at the family level using other behaviour change techniques and more direct strategies to reach parents. (c) 2015 World Obesity
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40.
  • Wallström, Sofia, 1988, et al. (författare)
  • ATOMIUM: Molecular inventory of 17 oxygen-rich evolved stars observed with ALMA
  • 2024
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 681
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The dusty winds of cool evolved stars are a major contributor of the newly synthesised material enriching the Galaxy and future generations of stars. However, the details of the physics and chemistry behind dust formation and wind launching have yet to be pinpointed. Recent spatially resolved observations show the importance of gaining a more comprehensive view of the circumstellar chemistry, but a comparative study of the intricate interplay between chemistry and physics is still difficult because observational details such as frequencies and angular resolutions are rarely comparable. Aims. Aiming to overcome these deficiencies, ATOMIUM is an ALMA Large Programme to study the physics and chemistry of the circumstellar envelopes of a diverse set of oxygen-rich evolved stars under homogeneous observing conditions at three angular resolutions between ∼0.02′1.4′. Here we summarize the molecular inventory of these sources, and the correlations between stellar parameters and molecular content. Methods. Seventeen oxygen-rich or S-Type asymptotic giant branch (AGB) and red supergiant (RSG) stars have been observed in several tunings with ALMA Band 6, targeting a range of molecules to probe the circumstellar envelope and especially the chemistry of dust formation close to the star. We systematically assigned the molecular carriers of the spectral lines and measured their spectroscopic parameters and the angular extent of the emission of each line from integrated intensity maps. Results. Across the ATOMIUM sample, we detect 291 transitions of 24 different molecules and their isotopologues. This includes several first detections in oxygen-rich AGB/RSG stars: PO v = 1, SO2 v1 = 1 and v2 = 2, and several high energy H2O transitions. We also find several first detections in S-Type AGB stars: vibrationally excited HCN v2 = 2,3 and SiS v = 4,5,6, as well as first detections of the molecules SiC, AlCl, and AlF in W Aql. Overall, we find strong correlations between the following molecular pairs: CS and SiS, CS and AlF, NaCl and KCl, AlO and SO, SO2 and SO, and SO2 and H2O; meaning both molecules tend to have more detected emission lines in the same sources. The measured isotopic ratios of Si and S are found to be consistent with previous measurements, except for an anomalously high 29Si/30Si ratio of 4 ± 1 in the RSG VX Sgr. Conclusions. This paper presents the overall molecular inventory and an initial analysis of the large ATOMIUM dataset, laying the groundwork for future work deriving molecular abundances and abundance profiles using radiative transfer modeling which will provide more rigorous tests for chemical models.
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41.
  • Anguille, Sébastien, et al. (författare)
  • Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
  • 2017
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:15, s. 1713-1721
  • Tidskriftsartikel (refereegranskat)abstract
    • Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age £65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD81 T cells. Long-term OS was correlated with interferon-g1 and tumor necrosis factor-a1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD81 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD81 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.
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42.
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43.
  • Bruggeman, C., et al. (författare)
  • Redox-active phases and radionuclide equilibrium valence state in subsurface environments - New insights from 6th EC FP IP FUNMIG
  • 2012
  • Ingår i: Applied Geochemistry. - : Elsevier BV. - 0883-2927 .- 1872-9134. ; 27:2, s. 404-413
  • Tidskriftsartikel (refereegranskat)abstract
    • Within the 6th EC FP Integrated Project "Fundamental Processes of Radionuclide Migration'' (FUNMIG), progress has been made to improve knowledge about the phases and reaction mechanisms involved in complex reduction processes of radionuclide contaminants in natural subsurface environments. This review paper gives an overview of the achievements made by the research groups involved in this project, and puts the scope and results of the studies in a more global context. Firstly, both thermodynamic and experimental evidence show that green rust is present and reactive in subsurface groundwater with a composition that spans the Fe(II)/Fe(III) redox boundary. Green rust has been shown to reduce Np(V), Se(VI) and Se(IV), but the pathways for the redox processes and the reaction products that result are complicated, and change as a function of the reaction parameters. Secondly, considerable evidence has emerged that Se(IV) is reduced on Fe(II)-bearing minerals which are ubiquitous in subsurface environments. The stable Se valence state in the presence of FeS(2) has been shown to be Se(0). Also, natural dissolved humic substances that contain sufficient electron donating capacity are capable of interacting with, and possibly reducing, Se(IV) to lower valence states. Thirdly, the influence of HCO(3)(-) and organic ligands on the uptake and reduction of U(VI) on Fe(II)-bearing minerals was investigated. While it appeared that HCO(3)(-) decreased the extent of U(VI) uptake by the reducing surface, the fraction of reduced U(IV) in the solid phase increased with increasing HCO(3)(-) concentration. In contrast with the observations for HCO(3)(-), organic ligands decreased both the extent of U uptake, as well as the fraction of U(IV) found in the solid phase. The studies performed within FUNMIG show that investigating reduction-oxidation mechanisms require (1) a detailed control over reaction conditions (anoxic atmosphere, purification of solid phases, initial radionuclide speciation), (2) a rigorous follow-up of reaction products (both solution chemistry and spectroscopic methods), and (3) the consideration of slow kinetics in the setting up of an experiment. These requirements make the study and assessment of redox processes one of the most demanding scientific challenges for geochemists who are asked to make predictions for radionuclide transport behaviour in the environment.
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44.
  • Danilovich, Taissa, 1987, et al. (författare)
  • Chemical tracers of a highly eccentric AGB–main-sequence star binary
  • 2024
  • Ingår i: Nature Astronomy. - 2397-3366.
  • Tidskriftsartikel (refereegranskat)abstract
    • Binary interactions have been proposed to explain a variety of circumstellar structures seen around evolved stars, including asymptotic giant branch (AGB) stars and planetary nebulae. Studies resolving the circumstellar envelopes of AGB stars have revealed spirals, disks and bipolar outflows, with shaping attributed to interactions with a companion. Here we use a combined chemical and dynamical analysis to reveal a highly eccentric and long-period orbit for W Aquilae, a binary system containing an AGB star and a main-sequence companion. Our results are based on anisotropic SiN emission, the detections of irregular NS and SiC emission towards the S-type star, and density structures observed in the CO emission. These features are all interpreted as having formed during periastron interactions. Our astrochemistry-based method can yield stringent constraints on the orbital parameters of long-period binaries containing AGB stars, and will be applicable to other systems.
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45.
  • De Bourdeaudhuij, I., et al. (författare)
  • Behavioural effects of a community-oriented setting-based intervention for prevention of childhood obesity in eight European countries. Main results from the IDEFICS study
  • 2015
  • Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:Suppl. 2, s. 30-40
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThe objective of this paper is to evaluate the behavioural effects, as reported by the parents of the participating boys and girls, of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) intervention. MethodsThe effectiveness of the IDEFICS intervention was evaluated through a cluster-controlled trial in eight European countries (control and intervention communities in each country) including more than 16,000 children. The 2- to 9.9-year-old children in the intervention group were exposed to a culturally adapted intervention that aimed to prevent childhood obesity through the community, schools/kindergartens and family. Parents completed questionnaires to measure water, soft drink and fruit juice intake; fruit and vegetable intake; daily TV viewing and other sedentary behaviours; daily physical activity levels and strengthening of the parent-child relationships at baseline and follow-up (2years later). Mixed models with an additional random effect for country were used to account for the clustered study design, and results were stratified by sex. ResultsThe pan-European analysis revealed no significant time by condition interaction effects, neither for boys nor girls, i.e. the analysis revealed no intervention effects on the behaviours of the IDEFICS children as reported by their parents (F=0.0 to 3.3, all p>0.05). Also very few significances were found in the country-specific analyses. Positive intervention effects were only found for sport club participation in Swedish boys, for screen time in weekends for Spanish boys and for TV viewing in Belgian girls. ConclusionAlthough no expected intervention effects as reported by the parents on diet, physical activity and sedentary behaviours could be shown for the overall IDEFICS cohort, a few favourable intervention effects were found on specific behaviours in some individual countries. More in-depth analyses of the process evaluation data are needed to obtain more insight into the relationship between the level of exposure to the intervention and its effect. (c) 2015 World Obesity
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46.
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47.
  • De Bourdeaudhuij, I., et al. (författare)
  • Implementation of the IDEFICS intervention across European countries: perceptions of parents and relationship with BMI
  • 2015
  • Ingår i: Obesity Reviews. - : Wiley. - 1467-7881. ; 16:Suppl. 2, s. 78-88
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesThe primary aim of the present study was to obtain insight into parents' perception of the IDEFICS intervention at the school or preschool/kindergarten and community levels and whether they received specific materials related to the intervention. The secondary aim was to analyse whether parents who reported higher levels of exposure to the IDEFICS intervention had children with more favourable changes in body mass index (BMI) z-scores between baseline and after 2years of intervention. MethodsProcess evaluation of the IDEFICS intervention investigated the implementation of the 2-year intervention in the intervention communities. Intervention group parents (n=4,180) in seven countries (Belgium, Cyprus, Estonia, Germany, Italy, Spain and Sweden) answered questions about their exposure to the IDEFICS study. To analyse the relationship between exposure and BMI z-score, a composite score was calculated for exposure at the setting and at the community levels. ResultsThe frequency of parental exposure to the IDEFICS messages not only through the community but also through the (pre)school/kindergarten was lower than what was intended and planned. The dose received by the parents was considerably higher through the (pre)school/kindergarten settings than that through the community in all countries. Efforts by the settings or communities related to fruit and vegetable consumption (range 69% to 97%), physical activity promotion (range 67% to 91%) and drinking water (range 49% to 93%) were more visible and also realized more parental involvement than those related to TV viewing, sleep duration and spending time with the family (below 50%). Results showed no relation of parental exposure at the setting or the community level on more favourable changes in children's BMI z-scores for the total sample. Country-specific analyses for parental exposure at the setting level showed an expected positive effect in German girls and an unexpected negative effect in Italian boys. ConclusionParental exposure and involvement in the IDEFICS intervention in all countries was much less than aimed for, which might be due to the diverse focus (six key messages) and high intensity and duration of the intervention. It may also be that the human resources invested in the implementation and maintenance of intervention activities by the study centres, the caretakers and the community stakeholders were not sufficient. Higher levels of parental exposure were not related to more favourable changes in BMI z-scores. (c) 2015 World Obesity
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48.
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49.
  • Haaland, S., et al. (författare)
  • Estimation of cold plasma outflow during geomagnetic storms
  • 2015
  • Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 120:12, s. 10622-10639
  • Tidskriftsartikel (refereegranskat)abstract
    • Low-energy ions of ionospheric origin constitute a significant contributor to the magnetospheric plasma population. Measuring cold ions is difficult though. Observations have to be done at sufficiently high altitudes and typically in regions of space where spacecraft attain a positive charge due to solar illumination. Cold ions are therefore shielded from the satellite particle detectors. Furthermore, spacecraft can only cover key regions of ion outflow during segments of their orbit, so additional complications arise if continuous longtime observations, such as during a geomagnetic storm, are needed. In this paper we suggest a new approach, based on a combination of synoptic observations and a novel technique to estimate the flux and total outflow during the various phases of geomagnetic storms. Our results indicate large variations in both outflow rates and transport throughout the storm. Prior to the storm main phase, outflow rates are moderate, and the cold ions are mainly emanating from moderately sized polar cap regions. Throughout the main phase of the storm, outflow rates increase and the polar cap source regions expand. Furthermore, faster transport, resulting from enhanced convection, leads to a much larger supply of cold ions to the near-Earth region during geomagnetic storms.
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50.
  • Haerens, L, et al. (författare)
  • Formative research to develop the IDEFICS physical activity intervention component: findings from focus groups with children and parents
  • 2010
  • Ingår i: Journal of Physical Activity and Health. - Champaign, IL : HUMAN KINETICS PUBL INC. - 1543-3080 .- 1543-5474. ; 7:2, s. 246-256
  • Tidskriftsartikel (refereegranskat)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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