Genetic and Epigenetic Landscape of Self-Identified Hispanics/Latino in All Of Us

English, A. C.; Fu, Y.; Paulin, L. F.; Izydorczyk, M. B.; Behera, S.; Li, Q.; Zheng, X.; Zhu, Y.; Paschall, J.; Tietz, G. E.; Honorato-Mauer, J.; Morina, L. B.; Griffith, S.; Pisupati, A.; Wang, S.; Dugan-Perez, S.; Shen, H.; Weissenberger, G. M.; Vee, V.; Gearhart, J.; Kokosinski, M.; Han, Y.; Myers, B.; Sanchez, A. M.; Mawhinney, M. Z.; Craig, B. D.; Marosy, B. A.; Mehta, H. H.; Garimella, K. V.; Khan, Z. M.; Venner, E.; Atkinson, E. G.; Gibbs, R. A.; Eichler, E. E.; Talkowski, M. E.; Doheny, K. F.; Muzny, D.; Schatz, M. C.; Metcalf, G. A.; Timp, W.; All of Us Research Program Long-Read Work

doi:10.64898/2026.10.30.763191

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bioRxiv · 10.64898/2026.10.30.763191

Genetic and Epigenetic Landscape of Self-Identified Hispanics/Latino in All Of Us

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Abstract

Human genetic studies still underrepresent many populations, limiting discovery and interpretation of medically relevant variation. Extensive admixture in self-identified Hispanic/Latino populations increases the need for representative reference data and ancestry-aware interpretation of medically relevant variation. We used long-read sequencing to analyze genetic variation, ancestry, and DNA methylation in 1,490 self-identified Hispanic/Latino participants from the All of Us Research Program. We identified 10 million novel variants and more than 100 candidate phenotype associations, with fine-mapping prioritizing structural variants over nearby single-nucleotide variants in more than half. We linked 3,329 tandem repeats to DNA methylation, resolved widespread allele-specific methylation, and identified ancestry-linked regulation across paralogous genes. These results reveal previously inaccessible genetic and regulatory variation and show the value of long-read sequencing for diverse populations.

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English, A. C., Fu, Y., Paulin, L. F., Izydorczyk, M. B., Behera, S., Li, Q., Zheng, X., Zhu, Y., Paschall, J., Tietz, G. E., Honorato-Mauer, J., Morina, L. B., Griffith, S., Pisupati, A., Wang, S., Dugan-Perez, S., Shen, H., Weissenberger, G. M., Vee, V., Gearhart, J., Kokosinski, M., Han, Y., Myers, B., Sanchez, A. M., Mawhinney, M. Z., Craig, B. D., Marosy, B. A., Mehta, H. H., Garimella, K. V., Khan, Z. M., Venner, E., Atkinson, E. G., Gibbs, R. A., Eichler, E. E., Talkowski, M. E., Doheny, K. F., Muzny, D., Schatz, M. C., Metcalf, G. A., Timp, W., All of Us Research Program Long-Read Work. 2026-11-02. Genetic and Epigenetic Landscape of Self-Identified Hispanics/Latino in All Of Us. https://doi.org/10.64898/2026.10.30.763191

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