Universidad Peruana Cayetano Heredia

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers

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dc.contributor.author Zollner, Linda
dc.contributor.author Boekstegers, Felix
dc.contributor.author Barahona Ponce, Carol
dc.contributor.author Scherer, Dominique
dc.contributor.author Marcelain, Katherine
dc.contributor.author Gárate-Calderón, Valentina
dc.contributor.author Waldenberger, Melanie
dc.contributor.author Morales, Erik
dc.contributor.author Rojas, Armando
dc.contributor.author Munoz, César
dc.contributor.author Retamales, Javier
dc.contributor.author De Toro, Gonzalo
dc.contributor.author Kortmann, Allan Vera
dc.contributor.author Barajas, Olga
dc.contributor.author Rivera, María Teresa
dc.contributor.author Cortés, Analía
dc.contributor.author Loader, Denisse
dc.contributor.author Saavedra, Javiera
dc.contributor.author Gutiérrez, Lorena
dc.contributor.author Ortega, Alejandro
dc.contributor.author Bertrán, Maria Enriqueta
dc.contributor.author Bartolotti, Leonardo
dc.contributor.author Gabler, Fernando
dc.contributor.author Campos, Mónica
dc.contributor.author Alvarado, Juan
dc.contributor.author Moisán, Fabricio
dc.contributor.author Spencer, Loreto
dc.contributor.author Nervi, Bruno
dc.contributor.author Carvajal, Daniel
dc.contributor.author Losada, Héctor
dc.contributor.author Almau, Mauricio
dc.contributor.author Fernández, Plinio
dc.contributor.author Olloquequi, Jordi
dc.contributor.author Carter, Alice R.
dc.contributor.author Miquel Poblete, Juan Francisco
dc.contributor.author Bustos, Bernabe Ignacio
dc.contributor.author Fuentes Guajardo, Macarena
dc.contributor.author Gonzalez-Jose, Rolando
dc.contributor.author Bortolini, Maria Cátira
dc.contributor.author Acuña-Alonzo, Victor
dc.contributor.author Gallo López-Aliaga, Carla Maria
dc.contributor.author Ruiz Linares, Andres
dc.contributor.author Rothhammer, Francisco
dc.contributor.author Lorenzo Bermejo, Justo
dc.date.accessioned 2023-10-09T17:09:17Z
dc.date.available 2023-10-09T17:09:17Z
dc.date.issued 2023
dc.identifier.uri https://hdl.handle.net/20.500.12866/14221
dc.description.abstract A 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. en_US
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartofseries Cancers
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Gallbladder cancer en_US
dc.subject Gallstone disease en_US
dc.subject Genetic admixture en_US
dc.subject Indigenous South American Mapuche ancestry en_US
dc.subject Ancestry-informative markers en_US
dc.subject Causal inference en_US
dc.subject Instrumental variables en_US
dc.subject Mendelian randomization en_US
dc.title Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3390/cancers15164033
dc.relation.issn 2072-6694


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