323 research outputs found

    Conduites parentales de contrôle et sentiments dépressifs chez l'enfant

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    Plusieurs études indiquent que les pratiques parentales seraient reliées aux sentiments dépressifs de l'enfant. La présente étude vise à vérifier une série d'hypothèses à propos des conduites de contrôle. Celles-ci pourraient constituer un bon prédicteur des sentiments dépressifs et seraient perçues différemment par les membres de la famille. Quatre cent six enfants et leurs parents ont répondu à des questionnaires sur leur perception des conduites de contrôle et les enfants ont rempli un questionnaire évaluant leurs sentiments dépressifs. Les hypothèses sont testées par des analyses de régressions multiples. Les résultats indiquent que les conduites de contrôle prédisent 13% de la variance des sentiments dépressifs, mais que seules les perceptions des enfants quant au contrôle contribuent de façon significative. Ces résultats sont discutés en fonction de l'interdépendance des dimensions, des différences sexuelles et des hypothèses concernant l'impact des perceptions

    Network propagation for GWAS analysis:a practical guide to leveraging molecular networks for disease gene discovery

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    MOTIVATION: Genome-wide association studies (GWAS) have enabled large-scale analysis of the role of genetic variants in human disease. Despite impressive methodological advances, subsequent clinical interpretation and application remains challenging when GWAS suffer from a lack of statistical power. In recent years, however, the use of information diffusion algorithms with molecular networks has led to fruitful insights on disease genes.RESULTS: We present an overview of the design choices and pitfalls that prove crucial in the application of network propagation methods to GWAS summary statistics. We highlight general trends from the literature, and present benchmark experiments to expand on these insights selecting as case study three diseases and five molecular networks. We verify that the use of gene-level scores based on GWAS P-values offers advantages over the selection of a set of 'seed' disease genes not weighted by the associated P-values if the GWAS summary statistics are of sufficient quality. Beyond that, the size and the density of the networks prove to be important factors for consideration. Finally, we explore several ensemble methods and show that combining multiple networks may improve the network propagation approach.</p

    Network propagation for GWAS analysis:a practical guide to leveraging molecular networks for disease gene discovery

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    MOTIVATION: Genome-wide association studies (GWAS) have enabled large-scale analysis of the role of genetic variants in human disease. Despite impressive methodological advances, subsequent clinical interpretation and application remains challenging when GWAS suffer from a lack of statistical power. In recent years, however, the use of information diffusion algorithms with molecular networks has led to fruitful insights on disease genes.RESULTS: We present an overview of the design choices and pitfalls that prove crucial in the application of network propagation methods to GWAS summary statistics. We highlight general trends from the literature, and present benchmark experiments to expand on these insights selecting as case study three diseases and five molecular networks. We verify that the use of gene-level scores based on GWAS P-values offers advantages over the selection of a set of 'seed' disease genes not weighted by the associated P-values if the GWAS summary statistics are of sufficient quality. Beyond that, the size and the density of the networks prove to be important factors for consideration. Finally, we explore several ensemble methods and show that combining multiple networks may improve the network propagation approach.</p

    Using eQTL weights to improve power for genome-wide association studies: a genetic study of childhood asthma

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    Increasing evidence suggests that single nucleotide polymorphisms (SNPs) associated with complex traits are more likely to be expression quantitative trait loci (eQTLs). Incorporating eQTL information hence has potential to increase power of genome-wide association studies (GWAS). In this paper, we propose using eQTL weights as prior information in SNP based association tests to improve test power while maintaining control of the family-wise error rate (FWER) or the false discovery rate (FDR). We apply the proposed methods to the analysis of a GWAS for childhood asthma consisting of 1296 unrelated individuals with German ancestry. The results confirm that eQTLs are enriched for previously reported asthma SNPs. We also find that some SNPs are insignificant using procedures without eQTL weighting, but become significant using eQTL-weighted Bonferroni or Benjamini–Hochberg procedures, while controlling the same FWER or FDR level. Some of these SNPs have been reported by independent studies in recent literature. The results suggest that the eQTL-weighted procedures provide a promising approach for improving power of GWAS. We also report the results of our methods applied to the large-scale European GABRIEL consortium data

    Physiological and affective responses of 30s‒30s intermittent small-sided game in elite handball players: A new alternative to intermittent running

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    Objectives: To compare physiological and affective demands of a novel small-sided game designed in intermittent (30s‒30s) regimen opposing 3-a-side field players with 30s‒30s shuttle running and handball match play. Methods: Fourteen elite male handball players (age 23.8 ± 4.4 y; body mass 84.0 ± 7.4 kg; height 188 ± 0.06 m) performed 2 periods of 10-min of each experimental exercise in separate occasions. Physiological demand was assessed using mean heart rate, time spent in heart rate intensity zones and post-exercise blood lactate concentration. The difference between ‘perceived exertion’ and ‘pleasure’ determined the affective balance. Results: Small-sided game and shuttle running drills showed similar mean heart rate (88.8 ±2.4 and 90.4 ±2.8 % of peak heart rate, respectively) and time spent in heart rate zones. The match play elicited lower mean heart rate (86.9 ± 3.4 % of peak heart rate, P ≤ 0.05, large ES) than small-sided game and shuttle running. Peak lactate for small-sided game (6.6 ±2.6 mmol/L) was lower than shuttle running (10 ±2.2 mmol/L, P ≤ 0.05, large ES) whereas no significant difference was observed with match play. The small-sided game showed lower affective balance than shuttle running (P ≤ 0.01, large ES). Conclusions: Coaches can be confident in prescribing the small-sided game as a suitable alternative to shuttle running to provide consistent aerobic stimulus with lower affective balance. The small-sided game may be considered as a specific training method in achieving relevant physiological adaptations for handball match play

    EGEA Collection: A Biobank Devoted to Asthma and Asthma-related Phenotypes

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    The Epidemiological study on the Genetics and Environment of Asthma (EGEA) is a 20-year cohort including cases with asthma (n = 388), their first degree relatives (n = 1244) and population-based controls (n = 415) recruited in the early 90’s from five French cities. Participants were extensively characterized regarding environment and respiratory health, and a specific effort was made to trace and bank biological samples (ISO 9001 certification since 2006). Access to data and samples is opened to researchers wishing to develop new scientific collaborative programs. The survey has already led to more than a hundred papers with almost one third in collaboration with national and international teams.</p

    Identification of OCA2 as a novel locus for the co-morbidity of asthma-plus-eczema

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    Background: Numerous genes have been associated with the three most common allergic diseases (asthma, allergic rhinitis or eczema) but these genes explain only a part of the heritability. In the vast majority of genetic studies, complex phenotypes such as co- morbidity of two of these diseases, have not been considered. This may partly explain missing heritability. Objective: To identify genetic variants specifically associated with the co-morbidity of asthma-plus-eczema. Methods: We first conducted a meta-analysis of four GWAS (Genome-Wide Association Study) of the combined asthma-plus-eczema phenotype (total of 8807 European-ancestry subjects of whom 1208 subjects had both asthma and eczema). To assess whether the association with SNP(s) was specific to the co- morbidity, we also conducted a meta-analysis of homogeneity test of association according to disease status (“asthma-plus-eczema” vs. the presence of only one disease “asthma only or eczema only”). We then used a joint test by combining the two test statistics from the co-morbidity-SNP association and the phenotypic heterogeneity of SNP effect meta-analyses. Results: Seven SNPs were detected for specific association to the asthma-plus-eczema co-morbidity, two with significant and five with suggestive evidence using the joint test after correction for multiple testing. The two significant SNPs are located in the OCA2 gene (Oculocutaneous Albinism II), a new locus never detected for significant evidence of association with any allergic disease. This gene is a promising candidate gene, because of its link to skin and lung diseases, and to epithelial barrier and immune mechanisms. Conclusion: Our study underlines the importance of studying sub-phenotypes as co-morbidities to detect new susceptibility genes

    Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

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    BACKGROUND: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. OBJECTIVE: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood. METHODS: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed. RESULTS: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P<5x10-6 ) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7 ), 14q22 (rs7493885 near NIN; P=2.9x10-6 ) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6 ). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings. CONCLUSION AND CLINICAL RELEVANCE: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms. This article is protected by copyright. All rights reserved

    Genome-wide interaction study of early-life smoking exposure on time-to-asthma onset in childhood

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    Background: Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early-life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. Objective: Our aim was to identify new loci interacting with ELTS exposure on time-to-asthma onset (TAO) in childhood.Methods: We conducted genome-wide interaction analyses of ELTS exposure on time-to-asthma onset in childhood in five European-ancestry studies (totaling 8,273 subjects) using Cox proportional-hazard model. The results of all five genome-wide analyses were meta-analyzed.Results: The 13q21 locus showed genome-wide significant interaction with ELTS exposure (P=4.3x10-8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P&lt;5x10-6) were found at three other loci: 20p12 (rs13037508 within MACROD2; P=4.9x10-7), 14q22 (rs7493885 near NIN; P=2.9x10-6) and 2p22 (rs232542 near CYP1B1; P=4.1x10-6). Functional annotations and the literature showed that the lead SNPs at these four loci influence DNA methylation in the blood and are located nearby CpG sites reported to be associated with exposure to tobacco smoke components, which strongly support our findings.Conclusion and Clinical Relevance: We identified novel candidate genes interacting with ELTS exposure on time-to-asthma onset in childhood. These genes have plausible biological relevance related to tobacco smoke exposure. Further epigenetic and functional studies are needed to confirm these findings and to shed light on the underlying mechanisms
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