A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities

Search for the standard model Higgs boson at LEP

The four LEP Collaborations, ALEPH, DELPHI, L3 and OPAL, have collected a total of 2461 pb(-1) of e(+)e(-) collision data at centre-of-mass energies between 189 and 209 GeV. The data are used to search for the Standard Model Higgs boson. The search results of the four Collaborations are combined and examined in a likelihood test for their consistency with two hypotheses: the background hypothesis and the signal plus background hypothesis. The corresponding confidences have been computed as functions of the hypothetical Higgs boson mass. A lower bound of 114.4 GeV/c(2) is established, at the 95% confidence level, on the mass of the Standard Model Higgs boson. The LEP data are also used to set upper bounds on the HZZ coupling for various assumptions concerning the decay of the Higgs boson. (C) 2003 Elsevier B.V. All rights reserved