775 resultados para DISCORDANT ASSOCIATIONS


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BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

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Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

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BACKGROUND: Risky single-occasion drinking (RSOD) is a prevalent and potentially harmful alcohol use pattern associated with increased alcohol use disorder (AUD). However, RSOD is commonly associated with a higher level of alcohol intake, and most studies have not controlled for drinking volume (DV). Thus, it is unclear whether the findings provide information about RSOD or DV. This study sought to investigate the independent and combined effects of RSOD and DV on AUD. METHODS: Data were collected in the longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) among 5598 young Swiss male alcohol users in their early twenties. Assessment included DV, RSOD, and AUD at two time points. Generalized linear models for binomial distributions provided evidence regarding associations of DV, RSOD, and their interaction. RESULTS: DV, RSOD, and their interaction were significantly related to the number of AUD criteria. The slope of the interaction was steeper for non/rare RSOD than for frequent RSOD. CONCLUSIONS: RSOD appears to be a harmful pattern of drinking, associated with increased AUD and it moderated the relationship between DV and AUD. This study highlighted the importance of taking drinking patterns into account, for both research and public health planning, since RSO drinkers constitute a vulnerable subgroup for AUD.

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BACKGROUND: Alcohol consumption--in particular drinking volume (DV) and risky single occasion drinking (RSOD)--has been related to a wide range of negative consequences and health problems. Previous studies also suggested that drinking in certain locations may be more strongly associated with the occurrence of alcohol-related harm than drinking in others. However, they were conducted in countries culturally and legally different from European countries and were limited to cross-sectional designs. This study investigates the cross-sectional and longitudinal associations of alcohol-related harm with DVs in different locations in a sample of young Swiss men. METHODS: A representative sample of 4536 young Swiss male drinkers completed baseline and 15-month follow-up questionnaires. These assessed DVs in 11 locations, alcohol-related harm (i.e. number of alcohol-related consequences and alcohol use disorder criteria) and frequency of RSOD. Cross-sectional and longitudinal associations of alcohol-related harm with DVs in each location were tested using regression models, with and without adjustment for frequency of RSOD. RESULTS: Both cross-sectional and longitudinal analyses showed significant positive associations between alcohol-related harm and DVs at friends' homes, in discos/nightclubs and in outdoor public places, when controlling for frequency of RSOD. In contrast, the contribution of DVs at one's own home and in restaurants was consistently not significant when adjusted for frequency of RSOD. When controlling for RSOD, associations between alcohol-related harm and DVs in bars/pubs, when playing sports, during other leisure activities, at cinemas/theatres, during sporting events, and during special events were not consistent between cross-sectional and longitudinal analyses. CONCLUSION: Results suggest that prevention interventions should not only target reducing the overall volume of alcohol consumed and the frequency of RSOD in general, but they should additionally focus on limiting alcohol consumption in outdoor public places, discos/nightclubs, and in friends' homes in particular, or at least on preventing harm occurring in these occasions.

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Objective: Frequent Emergency Department (ED) users are vulnerable individuals and discrimination is usually associated with increased vulnerability. The aim of this study was to investigate frequent ED users' perceptions of discrimination and to test whether they were associated with increased vulnerability. Methods: In total, 250 adult frequent ED users were interviewed in Lausanne University Hospital. From a previously published questionnaire, we assessed 15 dichotomous sources of perceived discrimination. Vulnerability was assessed using health status: objective health status (evaluation by a healthcare practitioner including somatic, mental health, behavioral, and social issues - dichotomous variables) and subjective health status [self-evaluation including health-related quality of life (WHOQOL) and quality of life (EUROQOL) - mean-scores]. We computed the prevalence rates of perceived discrimination and tested associations between perceived discrimination and health status (Fischer's exact tests, Mann-Whitney U-tests)

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Abstract Background: Little is known about how sitting time, alone or in combination with markers of physical activity (PA), influences mental well-being and work productivity. Given the need to develop workplace PA interventions that target employees’ health related efficiency outcomes; this study examined the associations between self-reported sitting time, PA, mental well-being and work productivity in office employees. Methods: Descriptive cross-sectional study. Spanish university office employees (n = 557) completed a survey measuring socio-demographics, total and domain specific (work and travel) self-reported sitting time, PA (International Physical Activity Questionnaire short version), mental well-being (Warwick-Edinburg Mental Well-Being Scale) and work productivity (Work Limitations Questionnaire). Multivariate linear regression analyses determined associations between the main variables adjusted for gender, age, body mass index and occupation. PA levels (low, moderate and high) were introduced into the model to examine interactive associations. Results: Higher volumes of PA were related to higher mental well-being, work productivity and spending less time sitting at work, throughout the working day and travelling during the week, including the weekends (p < 0.05). Greater levels of sitting during weekends was associated with lower mental well-being (p < 0.05). Similarly, more sitting while travelling at weekends was linked to lower work productivity (p < 0.05). In highly active employees, higher sitting times on work days and occupational sitting were associated with decreased mental well-being (p < 0.05). Higher sitting times while travelling on weekend days was also linked to lower work productivity in the highly active (p < 0.05). No significant associations were observed in low active employees. Conclusions: Employees’ PA levels exerts different influences on the associations between sitting time, mental well-being and work productivity. The specific associations and the broad sweep of evidence in the current study suggest that workplace PA strategies to improve the mental well-being and productivity of all employees should focus on reducing sitting time alongside efforts to increase PA.