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dc.contributor.author
Zollner, Linda
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Boekstegers, Felix
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Barahona Ponce, Carol
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Scherer, Dominique
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Marcelain, Katherine
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Gárate Calderón, Valentina
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Waldenberger, Melanie
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Morales, Erik
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Rojas, Armando
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Muñoz, César
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Alvarado, Juan
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Moisán, Fabricio
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Spencer, Loreto
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Nervi, Bruno
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Carvajal, Daniel
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Losada, Héctor
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Almau, Mauricio
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Fernández, Plinio
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Olloquequi, Jordi
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Carter, Alice R.
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Miquel Poblete, Juan Francisco
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Bustos, Bernabe Ignacio
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Fuentes Guajardo, Macarena
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Gonzalez-Jose, Rolando
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Bortolini, Maria Cátira
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Acuña Alonzo, Victor
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Gallo, Carla
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Ruiz-Linares, Andres
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Rothhammer, Francisco
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Lorenzo Bermejo, Justo
dc.date.available
2023-10-24T19:40:35Z
dc.date.issued
2023-08
dc.identifier.citation
Zollner, Linda; Boekstegers, Felix; Barahona Ponce, Carol; Scherer, Dominique; Marcelain, Katherine; et al.; Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers; Multidisciplinary Digital Publishing Institute; Cancers; 15; 16; 8-2023; 1-17
dc.identifier.uri
http://hdl.handle.net/11336/215815
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Multidisciplinary Digital Publishing Institute
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
ANCESTRY-INFORMATIVE MARKERS
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CAUSAL INFERENCE
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GALLBLADDER CANCER
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GALLSTONE DISEASE
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GENETIC ADMIXTURE
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INDIGENOUS SOUTH AMERICAN MAPUCHE ANCESTRY
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INSTRUMENTAL VARIABLES
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MENDELIAN RANDOMIZATION
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Genética y Herencia
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
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dc.title
Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-09-15T11:27:31Z
dc.identifier.eissn
2072-6694
dc.journal.volume
15
dc.journal.number
16
dc.journal.pagination
1-17
dc.journal.pais
Suiza
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dc.journal.ciudad
Basilea
dc.description.fil
Fil: Zollner, Linda. Ruprecht Karls Universitat Heidelberg; Alemania. German Cancer Research Center; Alemania
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Fil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; Alemania
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Fil: Barahona Ponce, Carol. Ruprecht Karls Universitat Heidelberg; Alemania
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Fil: Scherer, Dominique. Ruprecht Karls Universitat Heidelberg; Alemania
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Fil: Marcelain, Katherine. Universidad de Chile; Chile
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Fil: Gárate Calderón, Valentina. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; Chile
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Fil: Waldenberger, Melanie. German Research Center For Environmental Health; Alemania
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Fil: Morales, Erik. Hospital Regional de Talca; Chile. Universidad Católica de Maule; Chile
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Fil: Rojas, Armando. Universidad Católica de Maule; Chile
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Fil: Muñoz, César. Hospital Regional de Talca; Chile. Universidad Católica de Maule; Chile
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Fil: Alvarado, Juan. Hospital Regional de Concepción Dr. Guillermo Grant Benavente; Chile
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Fil: Moisán, Fabricio. Hospital Regional de Concepción Dr. Guillermo Grant Benavente; Chile
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Fil: Spencer, Loreto. Hospital Regional de Concepción Dr. Guillermo Grant Benavente; Chile
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Fil: Nervi, Bruno. Pontificia Universidad Católica de Chile; Chile
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Fil: Carvajal, Daniel. Universidad del Desarrollo; Chile
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Fil: Losada, Héctor. Universidad de La Frontera; Chile
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Fil: Almau, Mauricio. Hospital de Rancagua; Chile
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Fil: Fernández, Plinio. Hospital de Rancagua; Chile
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Fil: Olloquequi, Jordi. Universidad Autónoma de Chile; Chile. Universidad de Barcelona; España
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Fil: Carter, Alice R.. University of Bristol; Reino Unido
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Fil: Miquel Poblete, Juan Francisco. Pontificia Universidad Católica de Chile; Chile
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Fil: Bustos, Bernabe Ignacio. Northwestern University; Estados Unidos
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Fil: Fuentes Guajardo, Macarena. Universidad de Tarapacá; Chile
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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
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Fil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; Brasil
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Fil: Acuña Alonzo, Victor. National Institute Of Anthropology And History; México
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Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú
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Fil: Ruiz-Linares, Andres. Fudan University; China. Anthropologie Bio-Culturelle, Droit, Éthique et Santé; Francia. Colegio Universitario de Londres; Reino Unido
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Fil: Rothhammer, Francisco. Universidad de Tarapacá; Chile
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Fil: Lorenzo Bermejo, Justo. Ruprecht Karls Universitat Heidelberg; Alemania. Institut de Cancérologie Strasbourg Europe; Francia
dc.journal.title
Cancers
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2072-6694/15/16/4033
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/cancers15164033
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