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Optimal HLA imputation of admixed population with dimension reduction

Douillard, V.; dos Santos Brito Silva, N.; Bourguiba-Hachemi, S.; Naslavsky, M. S.; Scliar, M. O.; Duarte, Y. A. O.; Zatz, M.; Passos-Bueno, M. R.; Limou, S.; Gourraud, P.-A.; Launay, E.; Castelli, E. C.; SNP-HLA Reference Consortium (SHLARC), ; Vince, N.

2023-04-13 genomics
10.1101/2023.04.12.536582 bioRxiv
Show 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 1,000 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, (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 admixed populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.

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