A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.
Nat Genet
; 53(10): 1504-1516, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34611364
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Variación Genética
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Infecciones por VIH
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Mapeo Físico de Cromosoma
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Interacciones Huésped-Patógeno
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Genética de Población
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Antígenos HLA
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article