Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Genes and Immunity Année : 2020

Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection

Candelaria Vergara
Priya Duggal
Winston Timp
Eric Johnson
Michael Busch
Graeme Alexander
Georg Lauer
Matthew Cramp
  • Fonction : Auteur
Andrea Cox
Genevieve Wojcik

Résumé

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10-04) and rs8099917 (P value = 5.5 × 10-04). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10-05). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10-04). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917.

Dates et versions

hal-03550546 , version 1 (01-02-2022)

Identifiants

Citer

Candelaria Vergara, Priya Duggal, Chloe Thio, Ana Valencia, Thomas O’brien, et al.. Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection. Genes and Immunity, 2020, 21 (5), pp.348-359. ⟨10.1038/s41435-020-00115-3⟩. ⟨hal-03550546⟩
16 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More