1. Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection.
- Author
-
Huang H, Duggal P, Thio CL, Latanich R, Goedert JJ, Mangia A, Cox AL, Kirk GD, Mehta S, Aneja J, Alric L, Donfield SM, Cramp ME, Khakoo SI, Tobler LH, Busch M, Alexander GJ, Rosen HR, Edlin BR, Segal FP, Lauer GM, Thomas DL, Daly MJ, Chung RT, and Kim AY
- Subjects
- Europe, Female, Genome-Wide Association Study, Genotype, Hepacivirus genetics, Hepacivirus pathogenicity, Hepatitis C pathology, Hepatitis C virology, Humans, Interferons, Male, North America, Polymorphism, Single Nucleotide genetics, Genetic Predisposition to Disease, Hepatitis C genetics, Interleukins genetics, Major Histocompatibility Complex genetics
- Abstract
Approximately three quarters of acute hepatitis C (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/IFNL4 and the major histocompatibility complex (MHC) regions, with spontaneous clearance in the European population. We further fine-mapped the association in the MHC 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 MHC is stronger in samples from North America than those from Europe.
- Published
- 2017
- Full Text
- View/download PDF