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We present FELIX, a scalable framework for local-ancestry-aware genetic analysis that retains all participants without requiring discrete ancestry assignment. FELIX combines a compact ancestry-resolved genotype representation (FELIXla) with an adaptive association test that jointly evaluates shared-effect and ancestry-specific models at each variant (FELIXassoc). Simulations demonstrated well-calibrated inference under case-control imbalance and power that adapted to the locus-optimal model. Across 24 phenotypes in 240,038 All of Us participants, FELIX analyzed the 12.1% of individuals excluded by global-ancestry clustering and identified 15.4% more genome-wide significant loci than global-ancestry meta-analysis. Additional discoveries arose from recovering ancestry-specific haplotypes carried by admixed participants and from detecting ancestry-dependent marginal effects. Full-cohort effect estimates also improved polygenic score prediction across ancestries and traits.<\/jats:p>","DOI":"10.64898\/2026.08.09.26360047","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:10:11Z","timestamp":1786443011000},"source":"Crossref","is-referenced-by-count":0,"title":["A unified framework for local-ancestry-aware genetic association analysis across biobanks"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2898-9268","authenticated-orcid":false,"given":"Linfeng","family":"Hu","sequence":"first","affiliation":[{"name":"Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Analytic and 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