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

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.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos genetics
Publication Year Start




PMID- 28542165
OWN - NLM
STAT- In-Process
DA  - 20170525
LR  - 20170525
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Linking)
VI  - 13
IP  - 5
DP  - 2017 May
TI  - Subtypes of Native American ancestry and leading causes of death: Mapuche
      ancestry-specific associations with gallbladder cancer risk in Chile.
PG  - e1006756
LID - 10.1371/journal.pgen.1006756 [doi]
AB  - 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 = 6x10-27). 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.
FAU - Lorenzo Bermejo, Justo
AU  - Lorenzo Bermejo J
AUID- ORCID: http://orcid.org/0000-0002-6568-5333
AD  - Statistical Genetics Group, Institute of Medical Biometry and Informatics,
      University of Heidelberg, Heidelberg, Germany.
FAU - Boekstegers, Felix
AU  - Boekstegers F
AUID- ORCID: http://orcid.org/0000-0002-0587-7624
AD  - Statistical Genetics Group, Institute of Medical Biometry and Informatics,
      University of Heidelberg, Heidelberg, Germany.
FAU - Gonzalez Silos, Rosa
AU  - Gonzalez Silos R
AD  - Statistical Genetics Group, Institute of Medical Biometry and Informatics,
      University of Heidelberg, Heidelberg, Germany.
FAU - Marcelain, Katherine
AU  - Marcelain K
AD  - Program of Human Genetics, Institute of Biomedical Sciences, Medical Faculty,
      University of Chile, Santiago de Chile, Chile.
FAU - Baez Benavides, Pablo
AU  - Baez Benavides P
AD  - Program of Human Genetics, Institute of Biomedical Sciences, Medical Faculty,
      University of Chile, Santiago de Chile, Chile.
FAU - Barahona Ponce, Carol
AU  - Barahona Ponce C
AD  - Statistical Genetics Group, Institute of Medical Biometry and Informatics,
      University of Heidelberg, Heidelberg, Germany.
AD  - Program of Human Genetics, Institute of Biomedical Sciences, Medical Faculty,
      University of Chile, Santiago de Chile, Chile.
FAU - Muller, Bettina
AU  - Muller B
AUID- ORCID: http://orcid.org/0000-0002-8589-5725
AD  - Instituto Nacional del Cancer de Chile, Santiago de Chile, Chile.
FAU - Ferreccio, Catterina
AU  - Ferreccio C
AUID- ORCID: http://orcid.org/0000-0001-6331-5534
AD  - School of Medicine, Pontificia Universidad Catolica de Chile, Santiago de Chile, 
      Chile.
AD  - Advanced Center for Chronic Diseases, Santiago de Chile, Chile.
FAU - Koshiol, Jill
AU  - Koshiol J
AUID- ORCID: http://orcid.org/0000-0002-3832-6204
AD  - Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and
      Genetics, National Cancer Institute, Bethesda, Maryland, United States of
      America.
FAU - Fischer, Christine
AU  - Fischer C
AD  - Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
FAU - Peil, Barbara
AU  - Peil B
AD  - Statistical Genetics Group, Institute of Medical Biometry and Informatics,
      University of Heidelberg, Heidelberg, Germany.
FAU - Sinsheimer, Janet
AU  - Sinsheimer J
AD  - Biomathematics and Human Genetics Departments, David Geffen School of Medicine at
      UCLA, Los Angeles, California, United States of America.
FAU - Fuentes Guajardo, Macarena
AU  - Fuentes Guajardo M
AUID- ORCID: http://orcid.org/0000-0002-2486-1628
AD  - Instituto de Alta Investigacion, Tarapaca University, Arica, Chile.
AD  - Department of Genetics, Evolution and Environment, and UCL Genetics Institute,
      University College London, London, United Kingdom.
FAU - Barajas, Olga
AU  - Barajas O
AD  - Department of Internal Medicine, University Hospital of University of Chile,
      Santiago de Chile, Chile.
FAU - Gonzalez-Jose, Rolando
AU  - Gonzalez-Jose R
AD  - Centro Nacional Patagonico, Puerto Madryn, Argentina.
FAU - Bedoya, Gabriel
AU  - Bedoya G
AUID- ORCID: http://orcid.org/0000-0001-7281-3981
AD  - Laboratorio de Genetica Molecular, Facultad de Ciencias Exactas y Naturales,
      Universidad de Antioquia, Medellin, Colombia.
FAU - Catira Bortolini, Maria
AU  - Catira Bortolini M
AD  - Departamento de Genetica, Instituto de Biociencias Universidade Federal do Rio
      Grande do Sul, Puerto Alegre, Brazil.
FAU - Canizales-Quinteros, Samuel
AU  - Canizales-Quinteros S
AD  - Unidad de Genomica de Poblaciones Aplicada a la Salud, Facultad de Quimica,
      Universidad Nacional Autonoma de Mexico, Ciudad de Mexico, Mexico.
FAU - Gallo, Carla
AU  - Gallo C
AD  - Laboratorios de Investigacion y Desarrollo, Facultad de Ciencias y Filosofia,
      Universidad Peruana Cayetano Heredia, Lima, Peru.
FAU - Ruiz Linares, Andres
AU  - Ruiz Linares A
AD  - Department of Genetics, Evolution and Environment, and UCL Genetics Institute,
      University College London, London, United Kingdom.
FAU - Rothhammer, Francisco
AU  - Rothhammer F
AD  - Instituto de Alta Investigacion, Tarapaca University, Arica, Chile.
LA  - eng
PT  - Journal Article
DEP - 20170525
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
EDAT- 2017/05/26 06:00
MHDA- 2017/05/26 06:00
CRDT- 2017/05/26 06:00
PHST- 2016/12/23 [received]
PHST- 2017/04/11 [accepted]
AID - 10.1371/journal.pgen.1006756 [doi]
AID - PGENETICS-D-16-02821 [pii]
PST - epublish
SO  - PLoS Genet. 2017 May 25;13(5):e1006756. doi: 10.1371/journal.pgen.1006756.
      eCollection 2017 May.

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