Luo, YangKanai, MasahiroChoi, WansonLi, XinyiYamamoto, KenichiOgawa, KotaroGutierrez-Arcelus, MariaGregersen, Peter K.Stuart, Philip E.Elder, James T.Fellay, JacquesCarrington, MaryHaas, David W.Guo, XiuqingPalmer, Nicholette D.Chen, Yii-Der IdaRotter, Jerome. I.Taylor, Kent. D.Rich, Stephen. S.Correa, AdolfoWilson, James G.Kathiresan, SekarCho, Michael H.Metspalu, AndresEsko, TonuOkada, YukinoriHan, BuhmMcLaren, Paul J.Raychaudhuri, Soumya2023-08-162020-07-18Luo, Y., Kanai, M., Choi, W. et al. A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response. Nat Genet 53, 1504–1516 (2021). https://doi.org/10.1038/s41588-021-00935-7https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376810Fine-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 (GWAS) 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.en-USJournal Article2023-08-1610.1101/2020.07.16.20155606