Browsing by Author "Boekstegers, Felix"

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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 Ponce, Carol; Scherer, Dominique; Marcelain, Katherine; Gárate-Calderón, Valentina; Waldenberger, Melanie; Morales Mejías, Erik; Rojas, Armando; Muñoz, César; Retamales, Javier; Toro, Gonzalo De; Vera Kortmann, Allan; Barajas, Olga; Rivera, María Teresa; Cortés, Analía; Loader, Denisse; Saavedra, Javiera; Gutiérrez, Lorena; Ortega, Alejandro; Bertrán, María Enriqueta; Bartolotti, Leonardo; Gabler, Fernando; Campos, Mónica; Alvarado, Juan; Moisán, Fabricio; Spencer, María Loreto; Nervi Nattero, Bruno; Carvajal-Hausdorf, Daniel; Losada, Héctor; Almau, Mauricio; Fernández, Plinio; Olloquequi, Jordi; Carter, Alice R.; Miquel P., Juan Francisco; Bustos, Bernabé I.; Fuentes Guajardo, Macarena; Gonzalez-Jose, Rolando; Bortolini, Maria Cátira; Acuña-Alonzo, Victor; Gallo, Carla; Ruiz Linares, Andrés; Rothhammer, Francisco; Bermejo, Justo Lorenzo
    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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    PRDM15 Is Associated with Risk of Chronic Obstructive Pulmonary Disease in a Rural Population in Chile
    (KARGER, 2020) Hosgood, H. Dean, III; Diaz Pena, Roberto; Blansky, Deanna; Jaime, Sergio; Parra, Viviana; Boekstegers, Felix; Bermejo, Justo Lorenzo; Garcia Valero, Jose; Montes, Juan F.; Valdivia, Gonzalo; Miravitlles, Marc; Agusti, Alvar; Silva, Rafael S.; Olloquequi, Jordi
    Background: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with similar to 1% of Latin American ancestry. Objective: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. Method: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p <= 0.001), call rates (<95%), and minor allele frequencies (<0.5%) in controls, 455,564 markers were available for logistic regression. Results: PRDM15 rs1054761 C allele (p = 2.22 x 10(-7)) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10(-6)). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. Conclusion: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.
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    Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile
    (2017) Bermejo, Justo Lorenzo; Boekstegers, Felix; González Silos, Rosa; Marcelain, Katherine; Báez Benavides, Pablo; Barahona Ponce, Carol; Müller, Bettina; Ferreccio Readi, Catterina; Koshiol, Jill; Fischer, Christine