University of Iceland

About: University of Iceland is a education organization based out in Reykjavik, Suðurnes, Iceland. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 5423 authors who have published 16199 publications receiving 694762 citations. The organization is also known as: Háskóli Íslands.

Genome-wide association meta-analysis for total serum bilirubin levels

Abstract: Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism. We aimed to identify genetic contributors to variability in serum bilirubin levels by combining results from three genome-wide association studies (Framingham heart study, n = 3424; Rotterdam study, n = 3847; Age, Gene, Environment and Susceptibility-Reykjavik, n = 2193). Meta-analysis showed strong replication for a genetic influence on serum bilirubin levels of the UGT1A1 locus (P < 5 x 10(-324)) and a 12p12.2 locus. The peak signal in the 12p12.2 region was a non-synonymous SNP in SLCO1B1 (rs4149056, P = 6.7 x 10(-13)), which gives rise to a valine to alanine amino acid change leading to reduced activity for a hepatic transporter with known affinity for bilirubin. There were also suggestive associations with several other loci. The top variants in UGT1A1 and SLCO1B1 explain approximately 18.0 and approximately 1.0% of the variation in total serum bilirubin levels, respectively. In a conditional analysis adjusted for individual genotypes for the top UGT1A1 variant, the top SLCO1B1 variant remained highly significant (P = 7.3 x 10(-13)), but no other variants achieved genome-wide significance. In one of the largest genetic studies of bilirubin to date (n = 9464), we confirm the substantial genetic influence of UGT1A1 variants, consistent with past linkage and association studies, and additionally provide strong evidence of a role for allelic variation in SLCO1B1. Given the involvement of bilirubin in a number of physiological and disease processes, and the roles for UGT1A1 and SLCO1B1 in drug metabolism, these genetic findings have potential clinical importance. In analyses for association with gallbladder disease or gallstones, top bilirubin SNPs in UGT1A1 and SLCO1B1 were not associated.

Swift identification of dark gamma-ray bursts

Abstract: We present an optical flux vs. X-ray flux diagram for all known gamma-ray bursts (GRBs) for which an X-ray afterglow has been detected. We propose an operational definition of dark bursts as those bursts that are optically subluminous with respect to the fireball model, i.e., which have an optical-to-X-ray spectral indexOX < 0.5. Out of a sample of 52 GRBs we identify 5 dark bursts. The definition and diagram serve as a simple and quick diagnostic tool for identifying dark GRBs based on limited information, particularly useful for early and objective identification of dark GRBs observed with the Swift satellite. Subject headings: dust, extinction — galaxies: high-redshift — gamma rays: bursts large differences in localisation accuracies, localisation time since the onset of the burst, and search strate- gies. Moreover, effects of observing conditions (e.g., lu- nar phase) have generally not been taken into account in statistical studies. In many cases, GRBs have been con- sidered dark if no OA was detected, irrespective of how inefficient the search was. In fact, there is no generally accepted criterion for when a GRB is considered dark. With the launch of the Swift satellite it will be essential to have a quick diagnostic tool to flag dark bursts for im- mediate and/or detailed follow-up (including the near-IR bands) to ensure homogeneity of samples. In this Let- ter we present a GRB diagram of the optical flux (Fopt) vs. the X-ray flux (FX) and propose that those bursts which are optically subluminous with respect to the fire- ball model, i.e., which have an optical-to-X-ray spectral indexOX < 0.5, be defined as dark.

CUBN Is a Gene Locus for Albuminuria

Abstract: Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 × 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.

Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up

Abstract: Although preservation of the spleen following abdominal trauma and spleen-preserving surgical procedures have become gold standards, about 22,000 splenectomies are still conducted annually in the USA. Infections, mostly by encapsulated organisms, are the most well-known complications following splenectomy. Recently, thrombosis and cancer have become recognized as potential adverse outcomes post-splenectomy. Among more than 4 million hospitalized USA veterans, we assessed incidence and mortality due to infections, thromboembolism, and cancer including 8,149 cancer-free veterans who underwent splenectomy with a follow-up of up to 27 years. Relative risk estimates and 95% confidence intervals were calculated using time-dependent Poisson regression methods for cohort data. Splenectomized patients had an increased risk of being hospitalized for pneumonia, meningitis, and septicemia (rate ratios=1.9–3.4); deep venous thrombosis and pulmonary embolism (rate ratios=2.2); certain solid tumors: buccal, esophagus, liver, colon, pancreas, lung, and prostate (rate ratios =1.3–1.9); and hematologic malignancies: non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia (rate ratios =1.8–6.0). They also had an increased risk of death due to pneumonia and septicemia (rate ratios =1.6–3.0); pulmonary embolism and coronary artery disease (rate ratios =1.4–4.5); any cancer: liver, pancreas, and lung cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and any leukemia (rate ratios =1.3–4.7). Many of the observed risks were increased more than 10 years after splenectomy. Our results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.