Browsing by Author "Vera, Allan"

Now showing 1 - 3 of 3
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    Data Resource Profile: EULAT Eradicate GBC: the European-Latin American Research Consortium towards Eradication of Preventable Gallbladder Cancer
    (2025) Scherer, Dominique; Barahona, Carol; Mengoa, Claudio; Montenegro, Paola; Losada, Hector; Lineth, Ana; Rojas, Armando; Vera, Allan; Spencer, Loreto; Ortega, Alejandro; Vargas, Karina; Roa, Juan; Inklemona, Cristina; Colombo, Alicia; Kirsten, Romy; Zollner, Linda; Marcelain, Katherine; Rounge, Trine; Langseth, Hilde; Lewis, Sarah; Arroyo, Gerardo; Armisen, Ricardo; Nervi, Bruno; Muller, Bettina; Fernandez, Piga; Kumar, Rajiv; Salinas, Pamela; Kelly, Rachel; Jenab, Mazda; Bermejo, Justo
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    Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers
    (2023) Zollner, Linda; Boekstegers, Felix; Barahona, Carol; Scherer, Dominique; Marcelain, Katherine; Gárate, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, César; Retamales, Javier; De Toro, Gonzalo; Vera, Allan; Barajas, Olga; Rivera, María; Cortés, Analía; Loader, Denisse; Saavedra, Javiera; Gutiérrez, Lorena; Ortega, Alejandro; Bertrán, Maria; Bartolotti, Leonardo; Gabler, Fernando; Campos, Mónica; Alvarado, Juan; Moisán, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Olloquequi, Jordi; Carter, Alice; Miquel, Juan; Bustos, Bernabe; Fuentes, Macarena; Gonzalez, Rolando; Bortolini, Maria; Acuña, Victor; Gallo, Carla; Ruiz, Andres; Rothhammer, Francisco; Bermejo, Justo
    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.
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    Inbreeding and Gallbladder Cancer Risk: HomozygosityAssociations Adjusted for Indigenous American Ancestry, BMI,and Genetic Risk of Gallstone Disease
    (2024) Ceballos, Francisco; Boekstegers, Felix; Scherer, Dominique; Barahona, Carol; Marcelain, Katherine; Gárate, Valentina; Waldenberger, Melanie; Morales, Erik; Rojas, Armando; Munoz, César; Retamales, Javier; De Toro, Gonzalo; Vera, Allan; Barajas, Olga; Rivera, María; Cortés, Analía; Loader, Denisse; Saavedra, Javiera; Gutiérrez, Lorena; Ortega, Alejandro; Bertrán, Maria; Bartolotti, Leonardo; Gabler, Fernando; Campos, Mónica; Alvarado, Juan; Moisán, Fabricio; Spencer, Loreto; Nervi, Bruno; Carvajal-Hausdorf, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Olloquequi, Jordi; Salinas, Pamela; Bermejo, Justo
    Latin 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.

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