Luo, YangKanai, MasahiroChoi, WansonLi, XinyiSakaue, SaoriYamamoto, KenichiOgawa, KotaroGutierrez-Arcelus, MariaGregersen, Peter K.Stuart, Philip E.Elder, James T.Forer, LukasSchönherr, SebastianFuchsberger, ChristianSmith, Albert V.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, BuhmNHLBI Trans-Omics for Precision Medicine (TOPMed) ConsortiumMcLaren, Paul J.Raychaudhuri, Soumya2024-07-182024-07-182021Luo 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 [published correction appears in Nat Genet. 2021 Dec;53(12):1722. doi: 10.1038/s41588-021-00979-9]. Nat Genet. 2021;53(10):1504-1516. doi:10.1038/s41588-021-00935-7https://hdl.handle.net/1805/42309Fine-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.en-USPublisher PolicyHIV infectionsPhysical chromosome mappingAmino acidsHaplotypesLinkage disequilibriumArticle