Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10 −27 ). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data. Author summary A lot of attention has been paid to Latino heterogeneity related to individual proportions of Native American, European and African ancestry. The importance of the type of Native American ancestry for health, however, has hardly been studied. Here we examined genetic data from 2,039 admixed Chileans to investigate possible associations between top causes of death and the two major types of Native American ancestry in Chile. Our findings demonstrate the necessity of suitable surrogates for ancestry estimation which mirror the actual composition of the study population, and the advantage of considering fine-scale Latino heterogeneity for unraveling of disease etiology and personalized healthcare.
【초록키워드】 Asthma, Mortality, Population genetics, Cancer, Genetic, risk, diabetes, lung cancer, heterogeneity, genetics, Health, cancers, healthcare, African, Cancer patients, death, sensitivity analysis, skin, etiology, disease, association, genetic data, bronchus, Indigenous peoples, deaths, Larynx, lead, human population, gallbladder cancer, family history, Latin Americans, Latino, 95%CI, common disease, common diseases, decreased mortality, study population, proportions, increased mortality, healthy controls, heterogeneous, component, bladder, genome-wide genotype data, Gallbladder, European, identify, examined, proportion, increase in, cause, Increasing, associations, Chilean, Latin American, Native, 【제목키워드】 Cancer, risk, association, subtype, Gallbladder, cause, Native,