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The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and(More)
This guideline provides evidence-based key recommendations for diagnosis and therapy of gallstones and upgrades version 2000. It was developed by an interdisciplinary team of gastroenterologists, surgeons, radiologists, geneticists, external comparative quality assurance and patient support groups under the auspices of the German Society for Digestive and(More)
CONTEXT Chronic hepatitis C virus (HCV) infection outcomes include liver failure, hepatocellular carcinoma (HCC), and liver-related death. OBJECTIVE To assess the association between sustained virological response (SVR) and all-cause mortality in patients with chronic HCV infection and advanced hepatic fibrosis. DESIGN, SETTING, AND PATIENTS An(More)
BACKGROUND & AIMS Multidrug resistance-associated protein 2 (MRP2), a transporter of organic anions in hepatocytes, renal epithelial cells, and enterocytes, is differentially regulated in liver and kidney during cholestasis, but little is known about its regulation in the intestine. METHODS We investigated duodenal protein expression of MRP2 in male(More)
BACKGROUND & AIMS Because the mechanisms leading to bile duct damage in sclerosing cholangitis are unknown, we aimed to determine the pathogenesis of bile duct injury in multidrug resistance gene (Mdr2) (Abcb4) knockout mice (Mdr2(-/-)) as a novel model of the disease. METHODS Mdr2(-/-) and wild-type controls (Mdr2(+/+)) were studied at 2, 4, and 8 weeks(More)
Cholestatic liver diseases are caused by a range of hepatobiliary insults and involve complex interactions among environmental and genetic factors. Little is known about the pathogenic mechanisms of specific cholestatic diseases, which has limited our ability to manage patients with these disorders. However, recent genome-wide studies have provided insight(More)
This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus(More)
Cholic acid is a critical component of the lithogenic diet in mice. To determine its pathogenetic roles, we fed chow or 1% cholesterol with or without 0.5% cholic acid to C57L/J male mice, which because of lith genes have 100% gallstone prevalence rates. After 1 yr on the diets, we measured bile flow, biliary lipid secretion rates, hepatic cholesterol and(More)
BACKGROUND Nonalcoholic steatohepatitis (NASH) is a common disease with a poorly understood etiology, and the methionine-choline-deficient (MCD) diet is a nutritional model of NASH. Quantitative trait loci (QTL) analysis is a standard method for chromosomal mapping of polygenic disease traits. The purpose of this study is to administer mice an MCD diet in(More)