Repositorio
Institucional

Bermejo, Justo Lorenzo

Zollner, Linda

Boekstegers, Felix

Ponce, Carol Barahona

Scherer, Dominique

Marcelain, Katherine

Garate-Calderon, Valentina

Waldenberger, Melanie

Morales, Erik

Rojas, Armando

Munoz, Cesar

Retamales, Javier

De Toro, Gonzalo

Kortmann, Allan Vera

Barajas, Olga

Rivera, Maria Teresa

Cortes, Analia

Loader, Denisse

Saavedra, Javiera

Gutierrez, Lorena

Ortega, Alejandro

Bertran, Maria Enriqueta

Bartolotti, Leonardo

Gabler, Fernando

Campos, Monica

Alvarado, Juan

Moisan, Fabricio

Spencer, Loreto

Nervi, Bruno

Carvajal, Daniel

Losada, Hector

Almau, Mauricio

Fernandez, Plinio

Olloquequi, Jordi

Carter, Alice R.

Poblete, Juan Francisco Miquel

Bustos, Bernabe Ignacio

Guajardo, Macarena Fuentes

Gonzalez-Jose, Rolando

Bortolini, Maria Catira

Acuna-Alonzo, Victor

Gallo, Carla

Linares, Andres Ruiz

Rothhammer, Francisco

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

MDPI

CANCERS

en

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 x 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/m(2), 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.

2023

artículo original

10.3390/cancers15164033

PDF

gallbladder cancer

gallstone disease

genetic admixture

indigenous South American Mapuche ancestry

ancestry-informative markers

causal inference

instrumental variables

Mendelian randomization

Oncología

cáncer de vesícula biliar

enfermedad de cálculos biliares

mezcla genética

ascendencia indígena mapuche sudamericana

marcadores informativos de ascendencia

inferencia causal

variables instrumentales

Aleatorización mendeliana

artículo original

versión publicada

CC BY 4.0

CC BY 4.0

acceso abierto

acceso abierto

WOS:001063425200001

verde# dorado

Oncología

DFG INST 35/1314-1 FUGG

DFG INST 35/1503-1 FUGG