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Updated: Mar 30, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Advancing precision health discovery in a genetically diverse health system
Roni Haas1, Michael P Margolis2, Angela Wei3
1Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
None:
Linking genetic data with electronic health records in hospital biobanks promises to advance precision medicine, but limited ancestral diversity constrains discovery and generalizability. We analyzed 93,936 participants from the UCLA ATLAS Community Health Initiative to inform disease prevalence and genetic risk across five continental and 36 fine-scale ancestry groups. We discovered numerous unreported gene-phenotype associations, including FN3K with intestinal disaccharidase deficiency in Europeans and admixed Americans. Polygenic scores (PGS) robustly predicted common diseases, with effects markedly diminished in non-Europeans. Furthermore, we reduced the pronounced European bias in curated clinical variants using computational predictors, uncovering unreported disease-gene associations, including ANKZF1 and peripheral vascular disease in African Americans. Longitudinal data revealed that semaglutide efficacy varies across ancestries, is associated with PGS for type 2 diabetes, and is modulated by genetic variation in PTPRU. These findings illustrate how ancestrally diverse biobanks from a single health system yield robust disease associations and pharmacogenomic insights.
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