TY - JOUR T1 - Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection JF - bioRxiv DO - 10.1101/128975 SP - 128975 AU - Hailiang Huang AU - Priya Duggal AU - Chloe L. Thio AU - Rachel Latanich AU - James J. Goedert AU - Alessandra Mangia AU - Andrea L. Cox AU - Gregory D. Kirk AU - Shruti Mehta AU - Joel N. Blankson AU - Jasneet Aneja AU - Laurent Alric AU - Sharyne M. Donfield AU - Matthew E. Cramp AU - Salim I. Khakoo AU - Leslie H. Tobler AU - Michael Busch AU - Graeme J. Alexander AU - Hugo R. Rosen AU - Brian R. Edlin AU - Georg M. Lauer AU - David L. Thomas AU - Mark J. Daly AU - Raymond T. Chung AU - Arthur Y. Kim Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/20/128975.abstract N2 - Approximately three quarters of acute HCV infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using Immunochip in European and African ancestries. We confirmed two previously reported significant associations, in the IL28B/IFNL41,2 and MHC regions, with spontaneous clearance in the European population. We further fine-mapped the MHC association to a region of about 50 kilo base pairs, down from 1 mega base pairs in the previous study. Additional analyses suggested that the association in the MHC locus might be significantly stronger for virus subtype 1a than 1b, suggesting that viral subtype may have influenced the genetic mechanism underlying the clearance of HCV. ER -