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

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dc.contributor.authorZollner, Linda
dc.contributor.authorBoekstegers, Felix
dc.contributor.authorBarahona, Carol
dc.contributor.authorScherer, Dominique
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorGárate, 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.authorVera, Allan
dc.contributor.authorBarajas, Olga
dc.contributor.authorRivera, María
dc.contributor.authorCortés, Analía
dc.contributor.authorLoader, Denisse
dc.contributor.authorSaavedra, Javiera
dc.contributor.authorGutiérrez, Lorena
dc.contributor.authorOrtega, Alejandro
dc.contributor.authorBertrán, Maria
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-Hausdorf, Daniel
dc.contributor.authorLosada, Héctor
dc.contributor.authorAlmau, Mauricio
dc.contributor.authorFernández, Plinio
dc.contributor.authorOlloquequi, Jordi
dc.contributor.authorCarter, Alice
dc.contributor.authorMiquel, Juan
dc.contributor.authorBustos, Bernabe
dc.contributor.authorFuentes, Macarena
dc.contributor.authorGonzalez, Rolando
dc.contributor.authorBortolini, Maria
dc.contributor.authorAcuña, Victor
dc.contributor.authorGallo, Carla
dc.contributor.authorRuiz, Andres
dc.contributor.authorRothhammer, Francisco
dc.contributor.authorBermejo, Justo
dc.date.accessioned2024-05-16T18:16:41Z
dc.date.available2024-05-16T18:16:41Z
dc.date.issued2023
dc.descriptionGallo, Carla; Ruiz, Andres; Rothhammer, Francisco; Bermejo, Justo.
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.
dc.description.versionPublicada
dc.identifier.citationZollner, L.; Boekstegers, F.; Barahona Ponce, C.; Scherer, D.; Marcelain, K.; Gárate-Calderón, V.; Waldenberger, M.; Morales, E.; Rojas, A.; Munoz, C.; et al. Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers. Cancers 2023, 15, 4033. https:// doi.org/10.3390/cancers15164033
dc.identifier.doihttps://doi.org/10.3390/cancers15164033
dc.identifier.urihttps://hdl.handle.net/11447/8800
dc.language.isoen
dc.subjectMendelian randomization
dc.subjectAncestry-informative markers
dc.subjectCausal inference
dc.subjectGallbladder cancer
dc.subjectGallstone disease
dc.subjectGenetic admixture
dc.subjectIndigenous South American Mapuche ancestry
dc.subjectInstrumental variables
dc.titleGallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceCancers
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery8e2ee03b-003a-4e24-b577-290a5cd449c1

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