10.11588/data/IDSI88Lorenzo Bermejo, JustoJustoLorenzo Bermejo0000-0002-6568-5333Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyBoekstegers, FelixFelixBoekstegers0000-0002-0587-7624Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyGonzález Silos, RosaRosaGonzález SilosInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanyMarcelain, KatherineKatherineMarcelain Program of Human Genetics, Institute of Biomedical Sciences, Medical Faculty, University of Chile, Santiago de Chile, ChileBaez Benavides, PabloPabloBaez Benavides Program of Human Genetics, Institute of Biomedical Sciences, Medical Faculty, University of Chile, Santiago de Chile, ChileBarahona Ponce, CarolCarolBarahona PonceInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany, and Program of Human Genetics, Institute of Biomedical Sciences, Medical Faculty, University of Chile, Santiago de Chile, ChileMüller, BettinaBettinaMüller0000-0002-8589-5725 Instituto Nacional del Cáncer de Chile, Santiago de Chile, ChileFerreccio, CatterinaCatterinaFerreccio0000-0001-6331-5534School of Medicine, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile, and Advanced Center for Chronic Diseases, Santiago de Chile, ChileKoshiol, JillJillKoshiol0000-0002-3832-6204National Cancer Institute, Bethesda, Maryland, United States of AmericaFischer, ChristineChristineFischer Institute of Human Genetics, University of Heidelberg, Heidelberg, GermanyPeil, BarbaraBarbaraPeilInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, GermanySinsheimer, JanetJanetSinsheimerBiomathematics and Human Genetics Departments, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of AmericaFuentes Guajardo, MacarenaMacarenaFuentes Guajardo0000-0002-2486-1628Instituto de Alta Investigación, Tarapacá University, Arica, Chile, Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, United KingdomBarajas, OlgaOlgaBarajasDepartment of Internal Medicine, University Hospital of University of Chile, Santiago de Chile, ChileGonzalez-Jose, RolandoRolandoGonzalez-JoseCentro Nacional Patagónico, Puerto Madryn, ArgentinaBedoya, GabrielGabrielBedoya Laboratorio de Genética Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, ColombiaCátira Bortolini, MariaMariaCátira Bortolini Departamento de Genética, Instituto de Biociências Universidade Federal do Rio Grande do Sul, Puerto Alegre, BrazilCanizales-Quinteros, SamuelSamuelCanizales-QuinterosUnidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, MéxicoGallo, CarlaCarlaGallo Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, PerúRuiz Linares, AndresAndresRuiz LinaresDepartment of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, United KingdomRothhammer, FranciscoFranciscoRothhammerInstituto de Alta Investigación, Tarapacá University, Arica, ChileSubtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile [Dataset]heiDATA2018Medicine, Health and Life SciencesLorenzo Bermejo, Justo JustoLorenzo BermejoInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany2018-07-202018-10-2410.1371/journal.pgen.100675626307336100text/plaintext/plain1.1Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention.<P /> Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.