Amerindian Ancestry Influences Genetic Susceptibility to Chronic Obstructive Pulmonary Disease
Díaz-Peña, Roberto (Instituto de Investigación Sanitaria de Santiago (IDIS))
Boekstegers, Felix (Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg)
Silva, Rafael S. (Unidad Respiratorio, Centro de Diagnóstico Terapéutico, Hospital Regional de Talca)
Jaime, Sergio (Unidad Respiratorio, Centro de Diagnóstico Terapéutico, Hospital Regional de Talca)
Hosgood, H. Dean (Department of Epidemiology and Population Health, Albert Einstein College of Medicine)
Miravitlles, Marc (Hospital Universitari Vall d'Hebron)
Agustí, Àlvar (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Lorenzo Bermejo, Justo (Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg)
Olloquequi, Jordi (Universidad Autónoma de Chile. Instituto de Ciencias Biomédicas)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0. 05 to 5 × 10 −4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10 −3 to 3. 77 × 10 −8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Chronic obstructive pulmonary disease (COPD) ; Ancestry ; Autoimmunity ; Genome wide association studies (GWAS) ; Personalized medicine ; Hispanic paradox ; Immune dysfunction
Published in:	Journal of personalized medicine, Vol. 10 (august 2020) , ISSN 2075-4426

DOI: 10.3390/jpm10030093
PMID: 32824824

13 p, 1.3 MB

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