Genetic and Epigenetic Landscape of Self-Identified Hispanics/Latino in All Of Us
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.
Authors
- Yilei Fu (ORCID: https://orcid.org/0000-0002-7721-7027)
- Ziad Khan (ORCID: https://orcid.org/0000-0003-2173-9771)
- Luis F. Paulin (ORCID: https://orcid.org/0000-0003-2567-3773)
- Sairam Behera (ORCID: https://orcid.org/0000-0002-9047-0203)
- Evan E. Eichler (ORCID: https://orcid.org/0000-0002-8246-4014)
- Vanesa Vee
- Justin E. Paschall
- George Weissenberger (ORCID: https://orcid.org/0000-0002-3911-6823)
- Sean Griffith
- Ginger Metcalf (ORCID: https://orcid.org/0000-0002-8316-0071)
- Beth A. Marosy
- Michelle Mawhinney
- Fritz Joachim Sedlazeck (ORCID: https://orcid.org/0000-0001-6040-2691)
- Elizabeth G. Atkinson (ORCID: https://orcid.org/0000-0002-6308-776X)
- Brian Craig
- Qiuhui Li (ORCID: https://orcid.org/0009-0004-6740-8040)
- Grace E. Tietz (ORCID: https://orcid.org/0000-0003-3899-0444)
- Michael C. Schatz (ORCID: https://orcid.org/0000-0002-4118-4446)
- Richard A. Gibbs (ORCID: https://orcid.org/0000-0002-1356-5698)
- Michael E. Talkowski (ORCID: https://orcid.org/0000-0003-2889-0992)
- Kiran Garimella (ORCID: https://orcid.org/0000-0002-6212-5736)
- Heer Hemant Mehta (ORCID: https://orcid.org/0000-0002-5357-2112)
- Kimberly Floy Doheny (ORCID: https://orcid.org/0000-0001-8806-5738)
- Eric Venner (ORCID: https://orcid.org/0000-0002-3319-6690)
- Xinchang Zheng (ORCID: https://orcid.org/0000-0001-5739-861X)
- Luke B Morina (ORCID: https://orcid.org/0000-0003-4728-7152)
- Aishwarya Pisupati (ORCID: https://orcid.org/0000-0003-2302-8279)
- Winston Timp (ORCID: https://orcid.org/0000-0003-2083-6027)
- Shannon Dugan‐Perez (ORCID: https://orcid.org/0000-0003-1482-816X)
- Adam C. English (ORCID: https://orcid.org/0000-0003-2451-4375)
- Michal Izydorczyk (ORCID: https://orcid.org/0000-0003-3461-1224)
- Michelle Kokosinski
- Yiming Zhu
- Donna M. Muzny
- Jessica Gearhart
- Helen Shen (ORCID: https://orcid.org/0009-0003-4093-0480)
- Alice M. Sanchez
- Benjamin Myers
- Jessica Honorato-Mauer (ORCID: https://orcid.org/0000-0001-8043-2935)
- Siyu Wang (ORCID: https://orcid.org/0009-0006-3113-4054)
- Yi Han
Institutions
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Baylor College of Medicine (US)
- University of Washington (US)
- Johns Hopkins Medicine (US)
- Massachusetts General Hospital (US)
- Rice University (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-11-02
- DOI
- https://doi.org/10.64898/2026.10.30.763191
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- preprint