Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America
Abstract The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). I...
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doaj-485e978fbba34aad8e8f96a287674be52020-12-08T05:09:42ZengNature Publishing GroupScientific Reports2045-23222018-09-018111010.1038/s41598-018-32837-wGenome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin AmericaPablo Oliveira0Gustavo N. O. Costa1Andresa K. A. Damasceno2Fernando P. Hartwig3George C. G. Barbosa4Camila A. Figueiredo5Rita de C. Ribeiro-Silva6Alexandre Pereira7M. Fernanda Lima-Costa8Fernanda S. Kehdy9Eduardo Tarazona-Santos10Bernardo L. Horta11Laura C. Rodrigues12Rosemeire L. Fiaccone13Maurício L. Barreto14Institute of Collective Health, Federal University of BahiaInstitute of Collective Health, Federal University of BahiaInstitute of Collective Health, Federal University of BahiaPostgraduate Program in Epidemiology, Federal University of Pelotas, 464Center for Data Integration and Knowledge for Health, Oswaldo Cruz FoundationInstitute of Health Sciences, Federal University of BahiaNutrition School, Federal University of BahiaHeart Institute, University of São PauloRene Rachou Research Institute, Oswaldo Cruz FoundationLeprosy Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz FoundationInstitute of Biological Sciences, Federal University of Minas GeraisPostgraduate Program in Epidemiology, Federal University of Pelotas, 464Department of Infectious Disease Epidemiology, Faculty of Epidemiology, London School of Hygiene and Tropical MedicineDepartment of Statistics, Institute of Mathematics, Federal University of BahiaInstitute of Collective Health, Federal University of BahiaAbstract The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted an in silico functional analysis and found that this deletion spans several regulatory elements, including two promoter elements active in lung cells. In conclusion, we found robust evidence that CNVs could contribute for asthma susceptibility. These results uncover a new perspective on the influence of genetic factors modulating asthma risk.https://doi.org/10.1038/s41598-018-32837-wAsthma RiskPelotasSalvadoranAsthma OutcomesAsthma Symptoms |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pablo Oliveira Gustavo N. O. Costa Andresa K. A. Damasceno Fernando P. Hartwig George C. G. Barbosa Camila A. Figueiredo Rita de C. Ribeiro-Silva Alexandre Pereira M. Fernanda Lima-Costa Fernanda S. Kehdy Eduardo Tarazona-Santos Bernardo L. Horta Laura C. Rodrigues Rosemeire L. Fiaccone Maurício L. Barreto |
spellingShingle |
Pablo Oliveira Gustavo N. O. Costa Andresa K. A. Damasceno Fernando P. Hartwig George C. G. Barbosa Camila A. Figueiredo Rita de C. Ribeiro-Silva Alexandre Pereira M. Fernanda Lima-Costa Fernanda S. Kehdy Eduardo Tarazona-Santos Bernardo L. Horta Laura C. Rodrigues Rosemeire L. Fiaccone Maurício L. Barreto Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America Scientific Reports Asthma Risk Pelotas Salvadoran Asthma Outcomes Asthma Symptoms |
author_facet |
Pablo Oliveira Gustavo N. O. Costa Andresa K. A. Damasceno Fernando P. Hartwig George C. G. Barbosa Camila A. Figueiredo Rita de C. Ribeiro-Silva Alexandre Pereira M. Fernanda Lima-Costa Fernanda S. Kehdy Eduardo Tarazona-Santos Bernardo L. Horta Laura C. Rodrigues Rosemeire L. Fiaccone Maurício L. Barreto |
author_sort |
Pablo Oliveira |
title |
Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America |
title_short |
Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America |
title_full |
Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America |
title_fullStr |
Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America |
title_full_unstemmed |
Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America |
title_sort |
genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from latin america |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-09-01 |
description |
Abstract The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted an in silico functional analysis and found that this deletion spans several regulatory elements, including two promoter elements active in lung cells. In conclusion, we found robust evidence that CNVs could contribute for asthma susceptibility. These results uncover a new perspective on the influence of genetic factors modulating asthma risk. |
topic |
Asthma Risk Pelotas Salvadoran Asthma Outcomes Asthma Symptoms |
url |
https://doi.org/10.1038/s41598-018-32837-w |
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