A Rank-Based Nonparametric Method for Mapping Quantitative Trait Loci in Outbred Half-Sib Pedigrees: Application to Milk Production in a Granddaughter Design

We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated on a simulated dataset and its efficiency compared with interval mapping by using regression. It was shown that the rank-based approach is slightly inferior to regression when the residual variance is homoscedastic normal; however, in three out of four other scenarios envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed, and homoscedastic positively kurtosed, the latter outperforms the former one. Both methods were applied to a real data set analyzing the effect of bovine chromosome 6 on milk yield and composition by using a 125-cM map comprising 15 microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires

Delayed initiation of subcutaneous insulin therapy after failure of oral glucose-lowering agents in patients with Type 2 diabetes: a population-based analysis in the UK.

AIMS: The aim of this retrospective cohort study was to estimate the time to insulin initiation in patients with Type 2 diabetes inadequately controlled on oral glucose-lowering agents (OGLAs). METHODS: Insulin-naïve patients failing on OGLAs were identified from The Health Improvement Network database, which collects records from general practices throughout the UK. Patients were included if they were aged > or = 40 years, had concomitant prescriptions for > or = 2 OGLAs, and > or = 1 year of available records prior to the first occurrence of HbA(1c) > or = 8.0% after > or = 90 days of OGLA polytherapy at > or = 50% of maximum recommended dosages. RESULTS: A total of 2501 eligible patients with Type 2 diabetes who had an HbA(1c) above the OGLA failure threshold of > or = 8.0% were identified (54.0% male; 30.9% aged 60-69 years). It was estimated that if all the eligible patients were followed for 5 years, 25% would initiate insulin within 1.8 years of OGLA failure (95% CI 1.6-2.0), and 50% within 4.9 years (95% CI 4.6-5.8). The presence of diabetes-related complications had no substantial impact on the time to insulin initiation. CONCLUSIONS: This study found that 25% of patients with Type 2 diabetes had insulin initiation delayed for at least 1.8 years, and 50% of patients delayed starting insulin for almost 5 years after failure of glycaemic control with OGLA polytherapy, even in the presence of diabetes-related complications. Interventions that reduce this delay to insulin initiation are required to help achieve and maintain recommended glycaemic targets in patients with Type 2 diabetes

A rank-based nonparametric method for mapping quantitative trait loci in outbred half-sib pedigrees: application to milk production in a granddaughter design.

We describe the development of a multipoint nonparametric quantitative trait loci mapping method based on the Wilcoxon rank-sum test applicable to outbred half-sib pedigrees. The method has been evaluated on a simulated dataset and its efficiency compared with interval mapping by using regression. It was shown that the rank-based approach is slightly inferior to regression when the residual variance is homoscedastic normal; however, in three out of four other scenarios envisaged, i.e., residual variance heteroscedastic normal, homoscedastic skewed, and homoscedastic positively kurtosed, the latter outperforms the former one. Both methods were applied to a real data set analyzing the effect of bovine chromosome 6 on milk yield and composition by using a 125-cM map comprising 15 microsatellites and a granddaughter design counting 1158 Holstein-Friesian sires

An imprinted QTL with major effect on muscle mass and fat deposition maps to the IgfII locus in pigs

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