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

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

doi:10.1038/s41598-017-16011-2

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

Hailiang Huang
, Priya Duggal
, Chloe L. Thio
, Rachel Latanich
, James J. Goedert
, Alessandra Mangia
, Andrea L. Cox
, Gregory D. Kirk
, Shruti Mehta
, Jasneet Aneja
, Laurent Alric
, Sharyne M. Donfield
, Matthew E. Cramp
, Salim I. Khakoo
, Leslie H. Tobler
, Michael Busch
, Graeme J. Alexander
, Hugo R. Rosen
, Brian R. Edlin
, Florencia P. Segal

Georg M. Lauer, David L. Thomas, Mark J. Daly, Raymond T. Chung, Arthur Y. Kim

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Article number	15843
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-16011-2
State	Published - Dec 1 2017

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Huang, H., Duggal, P., Thio, C. L., Latanich, R., Goedert, J. J., Mangia, A., Cox, A. L., Kirk, G. D., Mehta, S., Aneja, J., Alric, L., Donfield, S. M., Cramp, M. E., Khakoo, S. I., Tobler, L. H., Busch, M., Alexander, G. J., Rosen, H. R., Edlin, B. R., ... Kim, A. Y. (2017). Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection. Scientific reports, 7(1), Article 15843. https://doi.org/10.1038/s41598-017-16011-2

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 & Kim, AY 2017, 'Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection', Scientific reports, vol. 7, no. 1, 15843. https://doi.org/10.1038/s41598-017-16011-2

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title = "Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection",

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.",

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

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AU - Huang, Hailiang

AU - Duggal, Priya

AU - Thio, Chloe L.

AU - Latanich, Rachel

AU - Goedert, James J.

AU - Mangia, Alessandra

AU - Cox, Andrea L.

AU - Kirk, Gregory D.

AU - Mehta, Shruti

AU - Aneja, Jasneet

AU - Alric, Laurent

AU - Donfield, Sharyne M.

AU - Cramp, Matthew E.

AU - Khakoo, Salim I.

AU - Tobler, Leslie H.

AU - Busch, Michael

AU - Alexander, Graeme J.

AU - Rosen, Hugo R.

AU - Edlin, Brian R.

AU - Segal, Florencia P.

AU - Lauer, Georg M.

AU - Thomas, David L.

AU - Daly, Mark J.

AU - Chung, Raymond T.

AU - Kim, Arthur Y.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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VL - 7

JO - Scientific reports

JF - Scientific reports

IS - 1

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

Abstract

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