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Emmi Helle Aldo Córdova-Palomera Tiina Ojala Priyanka Saha Praneetha Potiny Stefan Gustafsson Erik Ingelsson Michael Bamshad Deborah Nickerson Jessica X. Chong University of Washington Center for Mendelian Genomics Euan Ashley James R. Priest 《Genetic epidemiology》2019,43(2):215-226
Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes. 相似文献
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This paper proposes that an individual's self-assessed health (SAH) does not only suffer from systematic reporting bias and adaptation bias but is also biased owing to confounding health norm effects. Using 13 waves of the British Household Panel Survey covering the period 1991–2005, I show that, while there is a negative and statistically significant correlation between SAH and individuals' own health problem index, this negative effect reduces with the average number of health problems per (other) family member. The relative health bias is small, however, which implies that measures of SAH may not suffer seriously from systematic health norm bias. This is an important finding for researchers working with SAH data as it indicates that we do not have to worry too much about controlling for confounding influences from the health of other household members when estimating SAH regression equations. 相似文献
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C.K. Biswas J.M. Ramos D.N.S. Kerr 《Clinica chimica acta; international journal of clinical chemistry》1981,116(3):343-347
The effect of heparin on plasma ionised calcium was studied by adding it in increasing amounts to whole blood from 10 normal subjects. There was no significant change in ionised calcium from the addition of 1 U/ml but a significant fall of 0.02 mmol/1 when 2 U/ml were added and a progressive further fall with increasing concentrations. Heparin from three different manufacturers produced similar results. The effect of heparinisation in vivo was studied during regular haemodialysis on 10 patients with chronic renal failure. Following intravenous injection of 10000 U of heparin there was a consistent and significant fall averaging 0.03 mmol/l. 相似文献
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Seventy-eight patients with Burkitt's lymphoma and seventy controls from Ghana were typed for HLA-A, B, C and DR antigens, to determine whether there is an association between the HLA system and Burkitt's lymphoma. Increased relative risk was observed in Burkitt's lymphoma patients with DR7, HLA-A1 and B12 (BW44). 相似文献
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The relationship between depression and vitamin D deficiency is complex, with evidence mostly from studies affected by confounding and reverse causality. We examined the causality and direction of the relationship between 25-hydroxyvitamin D (25(OH)D) and depression in bi-directional Mendelian randomization (MR) analyses using information from up to 307,618 white British participants from the UK Biobank and summary results from the SUNLIGHT (n = 79,366) and Psychiatric Genomics consortia (PGC 113,154 cases and 218,523 controls). In observational analysis, the odds of depression decreased with higher 25(OH)D concentrations (adjusted odds ratio (OR) per 50% increase 0.95, 95%CI 0.94–0.96). In MR inverse variance weighted (IVW) using the UK Biobank, there was no association between genetically determined serum 25(OH)D and depression (OR per 50% higher 0.97, 95%CI 0.90–1.05) with consistent null association across all MR approaches and in data from PGC consortium. In contrast, genetic liability to depression was associated with lower 25(OH)D concentrations (MR IVW −3.26%, −4.94%–−1.55%), with the estimates remaining generally consistent after meta-analysing with the consortia. In conclusion, we found genetic evidence for a causal effect of depression on lower 25(OH)D concentrations, however we could not confirm a beneficial effect of nutritional vitamin D status on depression risk. 相似文献
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《Health & place》2021
The use of planning policy to manage and create a healthy food environment has become a popular policy tool for local governments in England. To date there has been no evaluation of their short-term impact on the built environment. We assess if planning guidance restricting new fast food outlets within 400 m of a secondary school, influences the food environment in the local authority of Newcastle Upon Tyne, UK. We have administrative data on all food outlets in Newcastle 3 years pre-intervention 2012–2015, the intervention year 2016, and three years’ post-intervention 2016–2019. We employ a difference-in-difference approach comparing postcodes within the school fast food outlet exclusion zone to those outside the fast-food exclusion zones. In the short term (3 years), planning guidance to limit the number of new fast-food outlets in a school exclusion zone did not have a statistically significant impact on the food environment when compared with a control zone. 相似文献