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

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dc.article.number4033
dc.catalogadorgjm
dc.contributor.authorZollner, Linda
dc.contributor.authorBoekstegers, Felix
dc.contributor.authorBarahona Ponce, Carol
dc.contributor.authorScherer, Dominique
dc.contributor.authorMarcelain, Katherine
dc.contributor.authorGárate-Calderón, Valentina
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorMorales Mejías, Erik
dc.contributor.authorRojas, Armando
dc.contributor.authorMuñoz, César
dc.contributor.authorRetamales, Javier
dc.contributor.authorToro, Gonzalo De
dc.contributor.authorVera Kortmann, Allan
dc.contributor.authorBarajas, Olga
dc.contributor.authorRivera, María Teresa
dc.contributor.authorCortés, Analía
dc.contributor.authorLoader, Denisse
dc.contributor.authorSaavedra, Javiera
dc.contributor.authorGutiérrez, Lorena
dc.contributor.authorOrtega, Alejandro
dc.contributor.authorBertrán, María Enriqueta
dc.contributor.authorBartolotti, Leonardo
dc.contributor.authorGabler, Fernando
dc.contributor.authorCampos, Mónica
dc.contributor.authorAlvarado, Juan
dc.contributor.authorMoisán, Fabricio
dc.contributor.authorSpencer, María Loreto
dc.contributor.authorNervi Nattero, 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 R.
dc.contributor.authorMiquel P., Juan Francisco
dc.contributor.authorBustos, Bernabé I.
dc.contributor.authorFuentes Guajardo, Macarena
dc.contributor.authorGonzalez-Jose, Rolando
dc.contributor.authorBortolini, Maria Cátira
dc.contributor.authorAcuña-Alonzo, Victor
dc.contributor.authorGallo, Carla
dc.contributor.authorRuiz Linares, Andrés
dc.contributor.authorRothhammer, Francisco
dc.contributor.authorBermejo, Justo Lorenzo
dc.date.accessioned2023-08-16T16:07:26Z
dc.date.available2023-08-16T16:07:26Z
dc.date.issued2023
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.fechaingreso.objetodigital2023-08-16
dc.format.extent17 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/cancers15164033
dc.identifier.urihttps://www.mdpi.com/2072-6694/15/16/4033
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/74402
dc.information.autorucEscuela de Medicina; Nervi Nattero, Bruno; 0000-0002-3016-7261; 604
dc.information.autorucEscuela de Medicina; Miquel P., Juan Francisco; 0000-0002-0526-4377; 72216
dc.issue.numero16
dc.language.isoen
dc.nota.accesoContenido completo
dc.revistaCancer
dc.rightsacceso abierto
dc.subjectGallbladder cancer
dc.subjectGallstone disease
dc.subjectGenetic admixture
dc.subjectIndigenous South American Mapuche ancestry
dc.subjectAncestry-informative markers
dc.subjectCausal inference
dc.subjectInstrumental variables
dc.subjectMendelian randomization
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleGallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers
dc.typeartículo
dc.volumen15
sipa.codpersvinculados604
sipa.codpersvinculados72216
sipa.trazabilidadORCID;2023-08-16
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