Mendelian Randomization Analysis of the Relationship Between Native American Ancestry and Gallbladder Cancer Risk

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dc.catalogadorpau
dc.contributor.authorZollner, L.
dc.contributor.authorBoekstegers, F.
dc.contributor.authorPonce, C.B.
dc.contributor.authorScherer, D.
dc.contributor.authorMarcelain, K.
dc.contributor.authorGárate-Calderón, V.
dc.contributor.authorWaldenberger, M.
dc.contributor.authorMorales, E.
dc.contributor.authorRojas, A.
dc.contributor.authorMunoz, C.
dc.contributor.authorMüller, B.
dc.contributor.authorRetamales, J.
dc.contributor.authorde Toro, G.
dc.contributor.authorKortmann, A.V.
dc.contributor.authorBarajas, O.
dc.contributor.authorRivera, M.T.
dc.contributor.authorCortés, A.
dc.contributor.authorLoader, D.
dc.contributor.authorSaavedra, J.
dc.contributor.authorGutiérrez, L.
dc.contributor.authorOrtega, A.
dc.contributor.authorBertrán, M.E.
dc.contributor.authorBartolotti, L.
dc.contributor.authorGabler, F.
dc.contributor.authorCampos, M.
dc.contributor.authorAlvarado, J.
dc.contributor.authorMoisán, F.
dc.contributor.authorSpencer, L.
dc.contributor.authorNervi Nattero, Bruno
dc.contributor.authorCarvajal, D.
dc.contributor.authorLosada, H.
dc.contributor.authorAlmau, M.
dc.contributor.authorFernández, P.
dc.contributor.authorOlloquequi, J.
dc.contributor.authorCarter, A.R.
dc.contributor.authorMiquel, Juan Francisco
dc.contributor.authorBustos, B.I.
dc.contributor.authorGuajardo, M.F.
dc.contributor.authorGonzalez-Jose, R.
dc.contributor.authorBortolini, M.C.
dc.contributor.authorAcuña-Alonzo, V.
dc.contributor.authorGallo, C.
dc.contributor.authorLinares, A.R.
dc.contributor.authorRothhammer, F.
dc.contributor.authorBermejo, J.L.
dc.date.accessioned2024-08-14T19:45:02Z
dc.date.available2024-08-14T19:45:02Z
dc.date.issued2022
dc.description.abstractBackground A strong association between the proportion of Native American 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 Native American people in Chile. We set out to investigate the causal association between Native American Mapuche ancestry and GBC risk, and the possible mediating effects of gallstone disease and body mass index (BMI) on this association. Methods Markers of Mapuche ancestry were selected based on the informativeness for assignment measure and then used as instrumental variables in two-sample mendelian randomization (MR) analyses and complementary sensitivity analyses. Result We found evidence of a causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% for every 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.6×10-5). Mapuche ancestry was also causally linked to gallstone disease (IVW risk increase of 3.6% per 1% increase in Mapuche proportion, 95% CI 3.1% to 4.0%, p = 1.0×10-59), suggesting a mediating effect of gallstones in the relationship between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative causal effect on BMI (IVW estimate -0.006 kg/m2 per 1% increase in Mapuche proportion, 95% CI -0.009 to -0.003, p = 4.4×10-5). Conclusions The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between Mapuche ancestry and GBC risk previously noted in observational studies appears to be causal, primary and secondary prevention strategies that take into account the individual proportion of Mapuche ancestry could be particularly efficient.
dc.fechaingreso.objetodigital2024-08-14
dc.fuente.origenORCID
dc.identifier.doi10.1101/2022.05.03.22274595
dc.identifier.urihttp://www.scopus.com/inward/record.url?eid=2-s2.0-85133062110&partnerID=MN8TOARS
dc.identifier.urihttps://doi.org/10.1101/2022.05.03.22274595
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/87432
dc.information.autorucEscuela de Medicina; Nervi Nattero, Bruno; 0000-0002-3016-7261; 604
dc.information.autorucEscuela de Medicina; Miquel, Juan Francisco; 0000-0002-0526-4377; 72216
dc.language.isoen
dc.nota.accesocontenido completo
dc.rightsacceso abierto
dc.subjectGenetic admixture
dc.subjectNative American Mapuche ancestry
dc.subjectGallbladder cancer
dc.subjectGallstone disease
dc.subjectMendelian randomization
dc.titleMendelian Randomization Analysis of the Relationship Between Native American Ancestry and Gallbladder Cancer Risk
dc.typepreprint
sipa.codpersvinculados604
sipa.codpersvinculados72216
sipa.trazabilidadORCID;2024-08-05
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