UGT1A1 is a major locus influencing bilirubin levels in African Americans

Total serum bilirubin is associated with several clinical outcomes, including cardiovascular disease, diabetes and drug metabolism. We conducted a genome-wide association study in 619 healthy unrelated African Americans in an attempt to replicate reported findings in Europeans and Asians and to identify novel loci influencing total serum bilirubin levels. We analyzed a dense panel of over two million genotyped and imputed SNPs in additive genetic models adjusting for age, sex, and the first two significant principal components from the sample covariance matrix of genotypes. Thirty-nine SNPs spanning a 78 kb region within the UGT1A1 displayed P-values <5 × 10−8. The lowest P-value was 1.7 × 10−22 for SNP rs887829. None of SNPs in the UGT1A1 remained statistically significant in conditional association analyses that adjusted for rs887829. In addition, SNP rs10929302 located in phenobarbital response enhancer module was significantly associated with bilirubin level with a P-value of 1.37 × 10−11; this enhancer module is believed to have a critical role in phenobarbital treatment of hyperbilirubinemia. Interestingly, the lead SNP, rs887829, is in strong linkage disequilibrium (LD) (r2≥0.74) with rs10929302. Taking advantage of the lower LD and shorter haplotypes in African-ancestry populations, we identified rs887829 as a more refined proxy for the causative variant influencing bilirubin levels. Also, we replicated the reported association between variants in SEMA3C and bilirubin levels. In summary, UGT1A1 is a major locus influencing bilirubin levels and the results of this study promise to contribute to understanding of the etiology and treatment of hyperbilirubinaemia in African-ancestry populations

Korea Institute of Ocean Science and Technology Earth System Model and Its Simulation Characteristics

We document the performance of a new earth system model developed at Korea Institute of Ocean Science and Technology, called the KIOST-ESM, based on a low-resolution (similar to 200 km for the atmosphere, similar to 100 km for the ocean) version of the Geophysical Fluid Dynamics Laboratory Climate Model 2.5. The main changes made to the base model include adopting a unified convection scheme for cumulus convection and an ocean mixed layer parameterization considering Langmuir circulation, which improve the model fidelity significantly. In addition, the KIOST-ESM adopts a new soil respiration scheme in the dynamic vegetation process of its land component. The performance of the KIOST-ESM was assessed in pre-industrial and historical simulations that are made as part of its participation in the Coupled Model Intercomparison Project phase 6 (CMIP6). The response of the earth system to increasing greenhouse gas concentrations was analyzed in the ScenarioMIP simulations. An abrupt quadrupling of CO2 experiment suggests that the equilibrium climate sensitivity of KIOST-ESM is 3.36 K-very close to the averaged one obtained from CMIP5 simulations. Although the KIOST-ESM showed a notable cold bias in the Northern Hemisphere and the double Inter-Tropical Convergence Zone bias, the KIOST-ESM outperforms the base model in simulating the mean sea surface temperature over the Southern Ocean and over the cold tongue in the tropical Pacific. The KIOST-ESM can also simulate the dominant tropical variability in intraseasonal (Madden-Julian Oscillation) and interannual (El Nino-Southern Oscillation) timescales more realistically