A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response
| Title: | A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response |
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| Authors: | Luo; Y; Kanai; M; Choi; W; Li; X; Sakaue; S; Yamamoto; K; Ogawa; Gutierrez-Arcelus; Gregersen; PK; Stuart; PE; Elder; JT; Forer; L; Schönherr; Fuchsberger; C; Smith; AV; Fellay; J; Carrington; Haas; DW; Guo; Palmer; ND; Chen; YDI; Rotter; JI; Taylor; KD; Rich; SS; Correa; A; Wilson; JG; Kathiresan; Cho; MH; Metspalu; Esko; T; Okada; Han; B; Abe; N; Abecasis; G; Aguet; F; Albert; Almasy; Alonso; Ament; Anderson; P; Anugu; Applebaum-Bowden; D; Ardlie; Dan; Arnett; DK; Ashley-Koch; Aslibekyan; Assimes; Auer; Avramopoulos; Ayas; Balasubramanian; Barnard; Barnes; Barr; RG; Barron-Casella; E; Barwick; Beaty; Beck; Becker; Beer; R; Beitelshees; Benjamin; Benos; Bezerra; Bielak; Bis; Blackwell; Blangero; Boerwinkle; Bowden; Bowler; Brody; Broeckel; U; Broome; Brown; Bunting; Burchard; Bustamante; Buth; Cade; Cardwell; Carey; V; Carrier; Carty; Casaburi; Romero; JPC; Casella; Castaldi; Chaffin; Chang; YC; Chasman; Chavan; BJ; WM; SH; Chuang; LM; Chung |
| Contributors: | Institute of Population Health Sciences |
| Publisher Information: | NATURE PORTFOLIO |
| Publication Year: | 2021 |
| Collection: | National Health Research Institutes (NHRI): Institutional Repository / 國家衛生研究院機構典藏 |
| 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 |
| File Description: | 7343259 bytes; application/pdf |
| Language: | English |
| Relation: | Nature Genetics. 2021 Oct 05;53(10):1504-1516.; http://ir.nhri.org.tw/handle/3990099045/15127; http://ir.nhri.org.tw/bitstream/3990099045/15127/1/SCP85116750590.pdf |
| DOI: | 10.1038/s41588-021-00935-7 |
| Availability: | http://ir.nhri.org.tw/handle/3990099045/15127; https://doi.org/10.1038/s41588-021-00935-7; http://ir.nhri.org.tw/bitstream/3990099045/15127/1/SCP85116750590.pdf |
| Accession Number: | edsbas.5FC27DBC |
| Database: | BASE |