PT  - JOURNAL ARTICLE
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
TI  - Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection
AID  - 10.1101/128975
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 128975
4099  - http://biorxiv.org/content/early/2017/04/20/128975.short
4100  - http://biorxiv.org/content/early/2017/04/20/128975.full
AB  - 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.