A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.
Details
State: Public
Version: Author's accepted manuscript
License: Not specified
Serval ID
serval:BIB_B110F32BA2DA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response.
Journal
Nature genetics
Working group(s)
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Contributor(s)
Abe N., Abecasis G., Aguet F., Albert C., Almasy L., Alonso A., Ament S., Anderson P., Anugu P., Applebaum-Bowden D., Ardlie K., Dan Arking X., Arnett D.K., Ashley-Koch A., Aslibekyan S., Assimes T., Auer P., Avramopoulos D., Ayas N., Balasubramanian A., Barnard J., Barnes K., Barr R.G., Barron-Casella E., Barwick L., Beaty T., Beck G., Becker D., Becker L., Beer R., Beitelshees A., Benjamin E., Benos T., Bezerra M., Bielak L., Bis J., Blackwell T., Blangero J., Boerwinkle E., Bowden D.W., Bowler R., Brody J., Broeckel U., Broome J., Brown D., Bunting K., Burchard E., Bustamante C., Buth E., Cade B., Cardwell J., Carey V., Carrier J., Carty C., Casaburi R., Romero JPC, Casella J., Castaldi P., Chaffin M., Chang C., Chang Y.C., Chasman D., Chavan S., Chen B.J., Chen W.M., Choi S.H., Chuang L.M., Chung M., Chung R.H., Clish C., Comhair S., Conomos M., Cornell E., Crandall C., Crapo J., Cupples L.A., Curran J., Curtis J., Custer B., Damcott C., Darbar D., David S., Davis C., Daya M., de Andrade M., Fuentes L.L., de Vries P., DeBaun M., Deka R., DeMeo D., Devine S., Dinh H., Doddapaneni H., Duan Q., Dugan-Perez S., Duggirala R., Durda J.P., Dutcher S.K., Eaton C., Ekunwe L., Boueiz A.E., Ellinor P., Emery L., Erzurum S., Farber C., Farek J., Fingerlin T., Flickinger M., Fornage M., Franceschini N., Frazar C., Fu M., Fullerton S.M., Fulton L., Gabriel S., Gan W., Gao S., Gao Y., Gass M., Geiger H., Gelb B., Geraci M., Germer S., Gerszten R., Ghosh A., Gibbs R., Gignoux C., Gladwin M., Glahn D., Gogarten S., Gong D.W., Goring H., Graw S., Gray K.J., Grine D., Gross C., Gu C.C., Guan Y., Gupta N., Haas D.M., Haessler J., Hall M., Han Y., Hanly P., Harris D., Hawley N.L., He J., Heavner B., Heckbert S., Hernandez R., Herrington D., Hersh C., Hidalgo B., Hixson J., Hobbs B., Hokanson J., Hong E., Hoth K., Hsiung C.A., Hu J., Hung Y.J., Huston H., Hwu C.M., Irvin M.R., Jackson R., Jain D., Jaquish C., Johnsen J., Johnson A., Johnson C., Johnston R., Jones K., Kang H.M., Kaplan R., Kardia S., Kelly S., Kenny E., Kessler M., Khan A., Khan Z., Kim W., Kimoff J., Kinney G., Konkle B., Kooperberg C., Kramer H., Lange C., Lange E., Lange L., Laurie C., Laurie C., LeBoff M., Lee J., Lee S., Lee W.J., LeFaive J., Levine D., Dan Levy X., Lewis J., Li X., Li Y., Lin H., Lin H., Lin X., Liu S., Liu Y., Liu Y., Loos RJF, Lubitz S., Lunetta K., Luo J., Magalang U., Mahaney M., Make B., Manichaikul A., Manning A., Manson J., Martin L., Marton M., Mathai S., Mathias R., May S., McArdle P., McDonald M.L., McFarland S., McGarvey S., McGoldrick D., McHugh C., McNeil B., Mei H., Meigs J., Menon V., Mestroni L., Metcalf G., Meyers D.A., Mignot E., Mikulla J., Min N., Minear M., Minster R.L., Mitchell B.D., Moll M., Momin Z., Montasser M.E., Montgomery C., Muzny D., Mychaleckyj J.C., Nadkarni G., Naik R., Naseri T., Natarajan P., Nekhai S., Nelson S.C., Neltner B., Nessner C., Nickerson D., Nkechinyere O., North K., O'Connell J., O'Connor T., Ochs-Balcom H., Okwuonu G., Pack A., Paik D.T., Pankow J., Papanicolaou G., Parker C., Peloso G., Peralta J.M., Perez M., Perry J., Peters U., Peyser P., Phillips L.S., Pleiness J., Pollin T., Post W., Becker J.P., Boorgula M.P., Preuss M., Psaty B., Qasba P., Qiao D., Qin Z., Rafaels N., Raffield L., Rajendran M., Ramachandran V.S., Rao D.C., Rasmussen-Torvik L., Ratan A., Redline S., Reed R., Reeves C., Regan E., Reiner A., Reupena M.S., Rice K., Robillard R., Robine N., Dan Roden X., Roselli C., Ruczinski I., Runnels A., Russell P., Ruuska S., Ryan K., Sabino E.C., Saleheen D., Salimi S., Salvi S., Salzberg S., Sandow K., Sankaran V.G., Santibanez J., Schwander K., Schwartz D., Sciurba F., Seidman C., Seidman J., Sériès F., Sheehan V., Sherman S.L., Shetty A., Shetty A., Sheu W.H., Shoemaker M.B., Silver B., Silverman E., Skomro R., Smith J., Smith J., Smith N., Smith T., Smoller S., Snively B., Snyder M., Sofer T., Sotoodehnia N., Stilp A.M., Storm G., Streeten E., Su J.L., Sung Y.J., Sylvia J., Szpiro A., Taliun D., Tang H., Taub M., Taylor M., Taylor S., Telen M., Thornton T.A., Threlkeld M., Tinker L., Tirschwell D., Tishkoff S., Tiwari H., Tong C., Tracy R., Tsai M., Vaidya D., Van Den Berg D., VandeHaar P., Vrieze S., Walker T., Wallace R., Walts A., Wang F.F., Wang H., Wang J., Watson K., Watt J., Weeks D.E., Weinstock J., Weir B., Weiss S.T., Weng L.C., Wessel J., Willer C., Williams K., Williams L.K., Wilson C., Wilson J., Winterkorn L., Wong Q., Wu J., Xu H., Yanek L., Yang I., Yu K., Zekavat S.M., Zhang Y., Zhao S.X., Zhao W., Zhu X., Zody M., Zoellner S.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
10/2021
Peer-reviewed
Oui
Volume
53
Number
10
Pages
1504-1516
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Alleles, Amino Acids/genetics, Gene Frequency/genetics, Genetic Variation, Genetics, Population, HIV Infections/genetics, HIV-1/genetics, HLA Antigens/genetics, Haplotypes/genetics, Host-Pathogen Interactions/genetics, Humans, Linkage Disequilibrium/genetics, Physical Chromosome Mapping, Reference Standards, Selection, Genetic, Viral Load
Pubmed
Web of science
Create date
12/10/2021 8:51
Last modification date
23/11/2022 7:14
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