| Title: |
A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response |
| Authors: |
Luo, Y; Kanai, M; Choi, W; Li, X; Sakaue, S; Yamamoto, K; Ogawa, K; Gutierrez-Arcelus, M; Gregersen, PK; Stuart, PE; Elder, JT; Forer, L; Schönherr, S; Fuchsberger, C; Smith, AV; Fellay, J; Carrington, M; Haas, DW; Guo, X; Palmer, ND; Chen, Y-DI; Rotter, JI; Taylor, KD; Rich, SS; Correa, A; Wilson, JG; Kathiresan, S; Cho, MH; Metspalu, A; Esko, T; Okada, Y; Han, B; McLaren, PJ; Raychaudhuri, S |
| Contributors: |
Consortium, NHLBI Trans-Omics for Precision Medicine (TOPMed) |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2022 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Fine-mapping to plausible causal variation may be more effective in multi-ancestry cohorts, particularly in the MHC, which has population-specific structure. To enable such studies, we constructed a large (n = 21,546) HLA reference panel spanning five global populations based on whole-genome sequences. Despite population-specific long-range haplotypes, we demonstrated accurate imputation at G-group resolution (94.2%, 93.7%, 97.8% and 93.7% in admixed African (AA), East Asian (EAS), European (EUR) and Latino (LAT) populations). Applying HLA imputation to genome-wide association study data for HIV-1 viral load in three populations (EUR, AA and LAT), we obviated effects of previously reported associations from population-specific HIV studies and discovered a novel association at position 156 in HLA-B. We pinpointed the MHC association to three amino acid positions (97, 67 and 156) marking three consecutive pockets (C, B and D) within the HLA-B peptide-binding groove, explaining 12.9% of trait variance. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41588-021-00935-7 |
| Availability: |
https://doi.org/10.1038/s41588-021-00935-7; https://ora.ox.ac.uk/objects/uuid:66bd1621-da12-4d01-b833-4397133eaf4b |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.5DE2297C |
| Database: |
BASE |