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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.26.609770
preprint
1
Article
Characterizing features affecting local ancestry inference performance in admixed populations
Honorato-Mauer Jessica http://orcid.org/0000-0001-8043-2935

Shah Nirav N.
Maihofer Adam X. http://orcid.org/0000-0003-4517-1623

Zai Clement C. http://orcid.org/0000-0003-0496-7262

Belangero Sintia http://orcid.org/0000-0002-2419-4351

Nievergelt Caroline M. http://orcid.org/0000-0001-5766-8923

Psychiatric Genomics Consortium for PTSD Ancestry Working Group
Santoro Marcos http://orcid.org/0000-0001-5714-9509

Atkinson Elizabeth http://orcid.org/0000-0002-6308-776X

27 8 2024
2024.08.26.609770https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.26.609770
nihpp-2024.08.26.609770.pdf
Abstract

In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using Local Ancestry Inference (LAI). Accurate LAI is crucial to ensure downstream analyses reflect the genetic ancestry of research participants accurately. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America’s primary continental ancestries – African (AFR), Amerindigenous (AMR), and European (EUR). Simulating LD-informed admixed haplotypes under a variety of 2 and 3-way admixture models, we implemented a standard LAI pipeline, testing three reference panel compositions to quantify their overall and ancestry-specific accuracy. We examined LAI miscall frequencies and true positive rates (TPR) across simulation models and continental ancestries. AMR tracts have notably reduced LAI accuracy as compared to EUR and AFR tracts in all comparisons, with TPR means for AMR ranging from 88-94%, EUR from 96-99% and AFR 98-99%. When LAI miscalls occurred, they most frequently erroneously called European ancestry in true Amerindigenous sites. Using a reference panel well-matched to the target population, even with a lower sample size, LAI produced true-positive estimates that were not statistically different from a high sample size but mismatched reference, while being more computationally efficient. While directly responsive to admixed Latin American cohort compositions, these trends are broadly useful for informing best practices for LAI across other admixed populations. Our findings reinforce the need for inclusion of more underrepresented populations in sequencing efforts to improve reference panels.
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pmc
