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

• 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
• Año de publicación: 2023
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ANCESTRY-INFORMATIVE MARKERS; CAUSAL INFERENCE; GALLBLADDER CANCER; GALLSTONE DISEASE; GENETIC ADMIXTURE; INDIGENOUS SOUTH AMERICAN MAPUCHE ANCESTRY; INSTRUMENTAL VARIABLES; MENDELIAN RANDOMIZATION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Zollner, Linda. Ruprecht Karls Universitat Heidelberg; Alemania. German Cancer Research Center; Alemania
Fil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; Alemania
Fil: Barahona Ponce, Carol. Ruprecht Karls Universitat Heidelberg; Alemania
Fil: Scherer, Dominique. Ruprecht Karls Universitat Heidelberg; Alemania
Fil: Marcelain, Katherine. Universidad de Chile; Chile
Fil: Gárate Calderón, Valentina. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; Chile
Fil: Waldenberger, Melanie. German Research Center For Environmental Health; Alemania
Fil: Morales, Erik. Hospital Regional de Talca; Chile. Universidad Católica de Maule; Chile
Fil: Rojas, Armando. Universidad Católica de Maule; Chile
Fil: Muñoz, César. Hospital Regional de Talca; Chile. Universidad Católica de Maule; Chile
Fil: Alvarado, Juan. Hospital Regional de Concepción Dr. Guillermo Grant Benavente; Chile
Fil: Moisán, Fabricio. Hospital Regional de Concepción Dr. Guillermo Grant Benavente; Chile
Fil: Spencer, Loreto. Hospital Regional de Concepción Dr. Guillermo Grant Benavente; Chile
Fil: Nervi, Bruno. Pontificia Universidad Católica de Chile; Chile
Fil: Carvajal, Daniel. Universidad del Desarrollo; Chile
Fil: Losada, Héctor. Universidad de La Frontera; Chile
Fil: Almau, Mauricio. Hospital de Rancagua; Chile
Fil: Fernández, Plinio. Hospital de Rancagua; Chile
Fil: Olloquequi, Jordi. Universidad Autónoma de Chile; Chile. Universidad de Barcelona; España
Fil: Carter, Alice R.. University of Bristol; Reino Unido
Fil: Miquel Poblete, Juan Francisco. Pontificia Universidad Católica de Chile; Chile
Fil: Bustos, Bernabe Ignacio. Northwestern University; Estados Unidos
Fil: Fuentes Guajardo, Macarena. Universidad de Tarapacá; Chile
Fil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina
Fil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Acuña Alonzo, Victor. National Institute Of Anthropology And History; México
Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú
Fil: Ruiz-Linares, Andres. Fudan University; China. Anthropologie Bio-Culturelle, Droit, Éthique et Santé; Francia. Colegio Universitario de Londres; Reino Unido
Fil: Rothhammer, Francisco. Universidad de Tarapacá; Chile
Fil: Lorenzo Bermejo, Justo. Ruprecht Karls Universitat Heidelberg; Alemania. Institut de Cancérologie Strasbourg Europe; Francia