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Inbreeding and Gallbladder Cancer Risk: HomozygosityAssociations Adjusted for Indigenous American Ancestry, BMI,and Genetic Risk of Gallstone Disease

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dc.contributor.authorCeballos, Francisco
dc.contributor.authorBoekstegers, Felix
dc.contributor.authorScherer, Dominique
dc.contributor.authorBarahona, Carol
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.authorSalinas, Pamela
dc.contributor.authorBermejo, Justo
dc.date.accessioned2025-08-19T14:58:27Z
dc.date.available2025-08-19T14:58:27Z
dc.date.issued2024
dc.description.abstractLatin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (FROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans. We calculated individual FROH above 1.5 Mb and weighted polygenic risk scores for GSD, and applied multiple logistic regression to assess the association between homozygosity and GBC risk. We found that homozygosity was due to a heterogeneous mixture of genetic drift and consanguinity in the study population. Although we found no association between homozygosity and overall GBC risk, we detected interactions of FROH with sex, age, and genetic risk of GSD that affected GBC risk. Specifically, the increase in GBC risk per 1% FROH was 19% in men (p-value = 0.002), 30% in those under 60 years of age (p-value = 0.001), and 12% in those with a genetic risk of GSD above the median (p-value = 0.01). The present study highlighted the complex interplay between inbreeding, genetic ancestry, and genetic risk of GSD in the development of GBC. The applied methodology and our findings underscored the importance of considering the population-specific genetic architecture, along with sex- and age-specific effects, when investigating the genetic basis of complex traits in Latin Americans.
dc.description.versionVersión Publicada
dc.identifier.citationCeballos F, Boekstegers F, Scherer D, Barahona Ponce C, Marcelain K, Gárate-Calderón V, Waldenberger M, Morales E, Rojas A, Munoz C, Retamales J, de Toro G, Vera Kortmann A, Barajas O, Rivera MT, Cortés A, Loader D, Saavedra J, Gutiérrez L, Ortega A, Bertrán ME, Bartolotti L, Gabler F, Campos M, Alvarado J, Moisán F, Spencer L, Nervi B, Carvajal-Hausdorf D, Losada H, Almau M, Fernández P, Olloquequi J, Salinas P, Lorenzo Bermejo J. Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease. Cancers (Basel). 2024 Dec 17;16(24):4195. doi: 10.3390/cancers16244195. PMID: 39766094
dc.identifier.doihttps://doi.org/10.3390/cancers16244195
dc.identifier.urihttps://hdl.handle.net/11447/10178
dc.language.isoen
dc.subjectAmerican ancestry
dc.subjectBMI
dc.subjectGallbladder cancer
dc.subjectInbreeding
dc.subjectRuns of homozygosity
dc.titleInbreeding and Gallbladder Cancer Risk: HomozygosityAssociations Adjusted for Indigenous American Ancestry, BMI,and Genetic Risk of Gallstone Disease
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceCancers
dspace.entity.typePublication
relation.isAuthorOfPublication8e2ee03b-003a-4e24-b577-290a5cd449c1
relation.isAuthorOfPublication.latestForDiscovery8e2ee03b-003a-4e24-b577-290a5cd449c1

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