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

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...

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Detalles Bibliográficos
Autores: Zollner, Linda, Boekstegers, Felix, Barahona Ponce, Carol, Scherer, Dominique, Marcelain, Katherine, Gárate Calderón, Valentina, Waldenberger, Melanie, Morales, Erik, Rojas, Armando, Muñoz, César, Alvarado, Juan, Moisán, Fabricio, Spencer, Loreto, Nervi, Bruno, Carvajal, Daniel, Losada, Héctor, Almau, Mauricio, Fernández, Plinio, Olloquequi, Jordi, Carter, Alice R., Miquel Poblete, Juan Francisco, Bustos, Bernabe Ignacio, Fuentes Guajardo, Macarena, Gonzalez-Jose, Rolando, Bortolini, Maria Cátira, Acuña Alonzo, Victor, Gallo, Carla, Ruiz-Linares, Andres, Rothhammer, Francisco, Lorenzo Bermejo, Justo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/215815
Acceso en línea:http://hdl.handle.net/11336/215815
Access Level:acceso abierto
Palabra clave:ANCESTRY-INFORMATIVE MARKERS
CAUSAL INFERENCE
GALLBLADDER CANCER
GALLSTONE DISEASE
GENETIC ADMIXTURE
INDIGENOUS SOUTH AMERICAN MAPUCHE ANCESTRY
INSTRUMENTAL VARIABLES
MENDELIAN RANDOMIZATION
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario: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.

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