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A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.
Luo, Yang; Kanai, Masahiro; Choi, Wanson; Li, Xinyi; Sakaue, Saori; Yamamoto, Kenichi; Ogawa, Kotaro; Gutierrez-Arcelus, Maria; Gregersen, Peter K; Stuart, Philip E; Elder, James T; Forer, Lukas; Schönherr, Sebastian; Fuchsberger, Christian; Smith, Albert V; Fellay, Jacques; Carrington, Mary; Haas, David W; Guo, Xiuqing; Palmer, Nicholette D; Chen, Yii-Der Ida; Rotter, Jerome I; Taylor, Kent D; Rich, Stephen S; Correa, Adolfo; Wilson, James G; Kathiresan, Sekar; Cho, Michael H; Metspalu, Andres; Esko, Tonu; Okada, Yukinori; Han, Buhm; McLaren, Paul J; Raychaudhuri, Soumya.
Afiliação
  • Luo Y; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. yangluo@broadinstitute.org.
  • Kanai M; Division of Rheumatology, Immunology, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. yangluo@broadinstitute.org.
  • Choi W; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. yangluo@broadinstitute.org.
  • Li X; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. yangluo@broadinstitute.org.
  • Sakaue S; Broad Institute of MIT and Harvard, Cambridge, MA, USA. yangluo@broadinstitute.org.
  • Yamamoto K; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Ogawa K; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gutierrez-Arcelus M; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Gregersen PK; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Stuart PE; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Elder JT; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
  • Forer L; Committee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL, USA.
  • Schönherr S; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Fuchsberger C; Division of Rheumatology, Immunology, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Smith AV; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Fellay J; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Carrington M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Haas DW; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Guo X; Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Palmer ND; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Chen YI; Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • Rotter JI; Center for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Taylor KD; Division of Rheumatology, Immunology, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Rich SS; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Correa A; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Wilson JG; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Kathiresan S; The Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Medical Research,North Short LIJ Health System, Manhasset, NY, USA.
  • Cho MH; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Metspalu A; Department of Dermatology, University of Michigan, Ann Arbor, MI, USA.
  • Esko T; Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, USA.
  • Okada Y; Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
  • Han B; Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
  • McLaren PJ; Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
  • Raychaudhuri S; Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Nat Genet ; 53(10): 1504-1516, 2021 10.
Article em 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Infecções por HIV / Mapeamento Físico do Cromossomo / Interações Hospedeiro-Patógeno / Genética Populacional / Antígenos HLA Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Variação Genética / Infecções por HIV / Mapeamento Físico do Cromossomo / Interações Hospedeiro-Patógeno / Genética Populacional / Antígenos HLA Limite: Humans Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos