Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile

PLoS Genet. 2017 May 25;13(5):e1006756. doi: 10.1371/journal.pgen.1006756. eCollection 2017 May.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Chile
  • Female
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / mortality
  • Genetics, Population
  • Genome, Human
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Indians, North American / genetics*
  • Latin America / epidemiology
  • Male
  • Risk Factors

Grants and funding

This study was financially supported by the German Federal Ministry of Education and Research (BMBF, grant 01DN15021), Germany’s Excellence Initiative of Heidelberg University within the program “Mobilitätsmaßnahmen im Rahmen internationaler Forschungskooperationen 2015-16”, the support program “Stiftungen und Preise” of the Ruprecht-Karls-Universität Heidelberg, the Deutsche Forschungsgemeinschaft and the Ruprecht-Karls-Universität Heidelberg within the funding program Open Access Publishing, and the German Research Foundation (DFG, grant LO 2061/1). Sample collection and storage was supported by the Biobank of University of Chile. JSS is partially funded by USA NIH Grant GM053275. This work was partially supported by general funds from the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (DCEG) and the Office of Research on Women’s Health (ORWH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.