Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection

Author:

Huang Hailiang,Duggal Priya,Thio Chloe L.,Latanich Rachel,Goedert James J.,Mangia Alessandra,Cox Andrea L.,Kirk Gregory D.,Mehta Shruti,Blankson Joel N.,Aneja Jasneet,Alric Laurent,Donfield Sharyne M.,Cramp Matthew E.,Khakoo Salim I.,Tobler Leslie H.,Busch Michael,Alexander Graeme J.,Rosen Hugo R.,Edlin Brian R.,Lauer Georg M.,Thomas David L.,Daly Mark J.,Chung Raymond T.,Kim Arthur Y.

Abstract

AbstractApproximately 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.

Publisher

Cold Spring Harbor Laboratory

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