Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan;103(1):e15282.
doi: 10.1111/tan.15282. Epub 2023 Nov 11.

Optimal population-specific HLA imputation with dimension reduction

Venceslas Douillard  1 , Nayane Dos Santos Brito Silva  1   2 , Sonia Bourguiba-Hachemi  1 , Michel S Naslavsky  3   4   5 , Marilia O Scliar  3 , Yeda A O Duarte  6   7 , Mayana Zatz  3   4 , Maria Rita Passos-Bueno  3   4 , Sophie Limou  1 , Pierre-Antoine Gourraud  1 , Élise Launay  1   8 , Erick C Castelli  2 , Nicolas Vince  1 ; SNP-HLA Reference Consortium (SHLARC)
Affiliations

Optimal population-specific HLA imputation with dimension reduction

Venceslas Douillard et al. HLA. 2024 Jan.

Abstract

Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, and (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 for HLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.

Keywords: Admixed populations; Dimension reduction; HLA imputation; Immunogenomics.

PubMed Disclaimer

References

REFERENCES

    1. Limou S, Zagury J-F. Immunogenetics: genome-wide Association of non-Progressive HIV and viral load control: HLA genes and beyond. Front Immunol. 2013;4:1-13.
    1. Fellay J, Shianna KV, Ge D, et al. A whole-genome association study of major determinants for host control of HIV-1. Science. 2007;317:944-947.
    1. International Multiple Sclerosis Genetics Consortium. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019;365(6460):eaav7188.
    1. Pairo-Castineira E et al. Genetic mechanisms of critical illness in COVID-19. Nature. 2021;591:92-98.
    1. COVID-19 host genetics initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021;600:472-477.

Publication types