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dc.contributor.authorZollner, Linda
dc.contributor.authorBoekstegers, Felix
dc.contributor.authorBarahona Ponce, Carol
dc.contributor.authorScherer, Dominique
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorGárate-Calderón, Valentina
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorMorales, Erik
dc.contributor.authorRojas, Armando
dc.contributor.authorMunoz, César
dc.contributor.authorRetamales, Javier
dc.contributor.authorDe Toro, Gonzalo
dc.contributor.authorKortmann, Allan Vera
dc.contributor.authorBarajas, Olga
dc.contributor.authorRivera, María Teresa
dc.contributor.authorCortés, Analía
dc.contributor.authorLoader, Denisse
dc.contributor.authorSaavedra, Javiera
dc.contributor.authorGutiérrez, Lorena
dc.contributor.authorOrtega, Alejandro
dc.contributor.authorBertrán, Maria Enriqueta
dc.contributor.authorBartolotti, Leonardo
dc.contributor.authorGabler, Fernando
dc.contributor.authorCampos, Mónica
dc.contributor.authorAlvarado, Juan
dc.contributor.authorMoisán, Fabricio
dc.contributor.authorSpencer, Loreto
dc.contributor.authorNervi, Bruno
dc.contributor.authorCarvajal, Daniel
dc.contributor.authorLosada, Héctor
dc.contributor.authorAlmau, Mauricio
dc.contributor.authorFernández, Plinio
dc.contributor.authorOlloquequi, Jordi
dc.contributor.authorCarter, Alice R.
dc.contributor.authorMiquel Poblete, Juan Francisco
dc.contributor.authorBustos, Bernabe Ignacio
dc.contributor.authorFuentes Guajardo, Macarena
dc.contributor.authorGonzalez-Jose, Rolando
dc.contributor.authorBortolini, Maria Cátira
dc.contributor.authorAcuña-Alonzo, Victor
dc.contributor.authorGallo, Carla
dc.contributor.authorRuiz Linares, Andres
dc.contributor.authorRothhammer, Francisco
dc.contributor.authorLorenzo Bermejo, Justo
dc.date.accessioned2024-04-10T01:45:06Z
dc.date.available2024-04-10T01:45:06Z
dc.date.issued2023
dc.identifier10.3390/cancers15164033
dc.identifier.issn20726694
dc.identifier.urihttps://hdl.handle.net/20.500.12728/10677
dc.description.abstractA strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10−5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate −0.006 kg/m2, 95% CI −0.009 to −0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient. © 2023 by the authors.es_ES
dc.description.sponsorshipBiobank of the University of Chile, (phs000810.v1.p1); National Heart, Lung, and Blood Institute, NHLBI; University of Miami, UM, (N01-HC65234); Northwestern University, NU, (N01-HC65236); San Diego State University, SDSU, (N01-HC65237); Albert Einstein College of Medicine, Yeshiva University, AECOM, (N01-HC65235); University of North Carolina Wilmington, UNCW, (N01-HC65233); Horizon 2020 Framework Programme, H2020, (825741); Deutsche Forschungsgemeinschaft, DFG, (INST 35/1314-1 FUGG, INST 35/1503-1 FUGG); Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg, MWKes_ES
dc.language.isoenes_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)es_ES
dc.subjectancestry-informative markerses_ES
dc.subjectcausal inferencees_ES
dc.subjectgallbladder canceres_ES
dc.subjectgallstone diseasees_ES
dc.subjectgenetic admixturees_ES
dc.subjectindigenous South American Mapuche ancestryes_ES
dc.subjectinstrumental variableses_ES
dc.subjectMendelian randomizationes_ES
dc.titleGallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markerses_ES
dc.typeArticlees_ES


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