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Sökning: WFRF:(Evans A) > Örebro universitet

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1.
  • Romagnoni, A, et al. (författare)
  • Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
  • Tidskriftsartikel (refereegranskat)abstract
    • Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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2.
  • Dieleman, J., et al. (författare)
  • Evolution and patterns of global health financing 1995-2014 : Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries
  • 2017
  • Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 389:10083, s. 1981-2004
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An adequate amount of prepaid resources for health is important to ensure access to health services and for the pursuit of universal health coverage. Previous studies on global health financing have described the relationship between economic development and health financing. In this study, we further explore global health financing trends and examine how the sources of funds used, types of services purchased, and development assistance for health disbursed change with economic development. We also identify countries that deviate from the trends. Methods: We estimated national health spending by type of care and by source, including development assistance for health, based on a diverse set of data including programme reports, budget data, national estimates, and 964 National Health Accounts. These data represent health spending for 184 countries from 1995 through 2014. We converted these data into a common inflation-adjusted and purchasing power-adjusted currency, and used non-linear regression methods to model the relationship between health financing, time, and economic development. Findings: Between 1995 and 2014, economic development was positively associated with total health spending and a shift away from a reliance on development assistance and out-of-pocket (OOP) towards government spending. The largest absolute increase in spending was in high-income countries, which increased to purchasing power-adjusted $5221 per capita based on an annual growth rate of 3.0%. The largest health spending growth rates were in upper-middle-income (5.9) and lower-middle-income groups (5.0), which both increased spending at more than 5% per year, and spent $914 and $267 per capita in 2014, respectively. Spending in low-income countries grew nearly as fast, at 4.6%, and health spending increased from $51 to $120 per capita. In 2014, 59.2% of all health spending was financed by the government, although in low-income and lower-middle-income countries, 29.1% and 58.0% of spending was OOP spending and 35.7% and 3.0% of spending was development assistance. Recent growth in development assistance for health has been tepid; between 2010 and 2016, it grew annually at 1.8%, and reached US$37.6 billion in 2016. Nonetheless, there is a great deal of variation revolving around these averages. 29 countries spend at least 50% more than expected per capita, based on their level of economic development alone, whereas 11 countries spend less than 50% their expected amount. Interpretation: Health spending remains disparate, with low-income and lower-middle-income countries increasing spending in absolute terms the least, and relying heavily on OOP spending and development assistance. Moreover, tremendous variation shows that neither time nor economic development guarantee adequate prepaid health resources, which are vital for the pursuit of universal health coverage. © The Author(s). Published by Elsevier Ltd.
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3.
  • 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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4.
  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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6.
  • Sigurdardottir, Lara G., et al. (författare)
  • Urinary melatonin levels, sleep disruption, and risk of prostate cancer in elderly men
  • 2015
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 67:2, s. 191-194
  • Tidskriftsartikel (refereegranskat)abstract
    • Melatonin has anticarcinogenic properties in experimental models. We undertook a case-cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26-12.98). These results require replication in larger prospective studies with longer follow-up.Patient summary: In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.
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7.
  • Barker, Adam, et al. (författare)
  • Association of genetic loci with glucose levels in childhood and adolescence a meta-analysis of over 6,000 children
  • 2011
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:6, s. 1805-1812
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS-A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS-Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level of 0.026 mrnol/L (0.021-0.031) for each unit increase in the score. CONCLUSIONS-Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards. Diabetes 60:1805-1812, 2011
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8.
  • Bertoldi, Bridget M., et al. (författare)
  • Relationship between resting heart rate and law enforcement involvement : The moderating role of socioeconomic status in a sample of urban youth
  • 2022
  • Ingår i: Journal of criminal justice. - : Elsevier. - 0047-2352 .- 1873-6203. ; 82
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Resting heart rate (RHR) is a well-established biological risk factor for criminal behavior. However, potential moderating effects of social risk factors like socioeconomic status on this relationship remain unclear. The current study sought to clarify the moderating impact of socioeconomic status on the relation between low RHR in childhood and adolescence and subsequent legal system involvement by young adulthood.Methods: A subset of twins and triplets from the Risk Factors for Antisocial Behavior (RFAB) project (N = 347) were utilized to test hypotheses. Logistic regression analyses were performed to test for a moderating effect of socioeconomic status on the relationship between RHR and later law enforcement involvement (trouble with police, arrest).Results: Resting HR and SES were individually associated with an increased likelihood of being in trouble with the police and being arrested. In addition, RHR and SES in adolescence interacted to predict trouble with the police and arrest history by young adulthood, such that low RHR predicted these outcomes among adolescents who remained in low SES backgrounds.Conclusions: Adolescents who remain in low socioeconomic backgrounds from childhood will be a particularly important group to target in terms of treatment efforts to prevent criminal behavior.
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9.
  • Bruder, CEG, et al. (författare)
  • High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH
  • 2001
  • Ingår i: Human Molecular Genetics. - Oxford, United Kingdom : Oxford University Press. - 0964-6906 .- 1460-2083. ; 1, s. 271-
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CON methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.
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10.
  • Evans, Brittany, et al. (författare)
  • Urbanicity is Associated with Behavioral and Emotional Problems in Elementary School-Aged Children
  • 2018
  • Ingår i: Journal of Child and Family Studies. - : Springer Science and Business Media LLC. - 1062-1024 .- 1573-2843. ; 27:7, s. 2193-2205
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract: Adults are 38% more likely to suffer from a psychiatric disorder when they live in an urban compared to a rural area. Urban upbringing may be particularly important. The aim of the present study was to examine whether urbanicity was independently associated with mental health in elementary school-aged children. Specifically, we investigated whether living in a more urban area was associated with exhibiting more behavioral and emotional problems, and whether this remained while controlling for other major risk factors for mental health problems in children. Data came from a Dutch general population study of children (n = 895). Information from four waves was used, in which children were aged approximately 8, 9, 11, and 12 years old. We used mixed effects models to assess the association between urbanicity and the outcomes of behavioral problems and emotional problems separately, while controlling for other major risk factors. The analyses showed that children who lived in more urban areas were significantly more likely to exhibit behavioral (p < .001) and emotional (p < .001) problems. This effect remained when controlling for neighborhood socioeconomic status, gender, ethnicity, family socioeconomic status, parental symptoms of psychopathology, parenting stress, and parenting practices (behavioral: p = .02, emotional: p = .009). In line with research in adults, urbanicity seems to be independently associated with behavioral and emotional problems in children. A possible underlying mechanism is that the city is a stressful environment for children to grow up in, which contributes to an increased risk for mental health problems.
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