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bioRxiv · 10.1101/2023.01.23.525129

Assessing HLA imputation accuracy in a West African population

Nanjala, R.·Mbiyavanga, M.·Hashim, S.·de Villiers, S.·Mulder, N.
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Abstract

The Human Leukocyte Antigen (HLA) region plays an important role in autoimmune and infectious diseases. HLA is a highly polymorphic region and thus difficult to impute. We therefore sought to evaluate HLA imputation accuracy, specifically in a West African population, since they are understudied and are known to harbor high genetic diversity. The study sets were selected from Gambian individuals within the Gambian Genome Variation Project (GGVP) Whole Genome Sequence datasets. Two different arrays, Illumina Omni 2.5 and Human Hereditary and Health in Africa (H3Africa), were assessed for the appropriateness of their markers, and these were used to test several imputation panels and tools. The reference panels were chosen from the 1000 Genomes dataset (1kg-All), 1000 Genomes African dataset (1kg-Afr), 1000 Genomes Gambian dataset (1kg-Gwd), H3Africa dataset and the HLA Multi-ethnic dataset. HLA-A, HLA-B and HLA-C alleles were imputed using HIBAG, SNP2HLA, CookHLA and Minimac4, and concordance rate was used as an assessment metric. Overall, the best performing tool was found to be HIBAG, with a concordance rate of 0.84, while the best performing reference panel was the H3Africa panel with a concordance rate of 0.62. Minimac4 (0.75) was shown to increase HLA-B allele imputation accuracy compared to HIBAG (0.71), SNP2HLA (0.51) and CookHLA (0.17). The H3Africa and Illumina Omni 2.5 array performances were comparable, showing that genotyping arrays have less influence on HLA imputation in West African populations. The findings show that using a larger population-specific reference panel and the HIBAG tool improves the accuracy of HLA imputation in West African populations. Author SummaryFor studies that associate a particular HLA type to a phenotypic trait for instance HIV susceptibility or control, genotype imputation remains the main method for acquiring a larger sample size. Genotype imputation, process of inferring unobserved genotypes, is a statistical technique and thus deals with probabilities. Also, the HLA region is highly variable and therefore difficult to impute. In view of this, it is important to assess HLA imputation accuracy especially in African populations. This is because the African genome has high diversity, and such studies have hardly been conducted in African populations. This work highlights that using HIBAG imputation tool and a larger population-specific reference panel increases HLA imputation accuracy in an African population.

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Nanjala, R., Mbiyavanga, M., Hashim, S., de Villiers, S., Mulder, N.. 2023-01-23. Assessing HLA imputation accuracy in a West African population. https://doi.org/10.1101/2023.01.23.525129

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