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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Asthma Risk Pelotas Salvadoran Asthma Outcomes Asthma Symptoms Medicine R Science Q
Acceso en línea:	https://doaj.org/article/485e978fbba34aad8e8f96a287674be5
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spelling	oai:doaj.org-article:485e978fbba34aad8e8f96a287674be52021-12-02T15:09:07ZGenome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America10.1038/s41598-018-32837-w2045-2322https://doaj.org/article/485e978fbba34aad8e8f96a287674be52018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32837-whttps://doaj.org/toc/2045-2322Abstract 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.Pablo OliveiraGustavo N. O. CostaAndresa K. A. DamascenoFernando P. HartwigGeorge C. G. BarbosaCamila A. FigueiredoRita de C. Ribeiro-SilvaAlexandre PereiraM. Fernanda Lima-CostaFernanda S. KehdyEduardo Tarazona-SantosBernardo L. HortaLaura C. RodriguesRosemeire L. FiacconeMaurício L. BarretoNature PortfolioarticleAsthma RiskPelotasSalvadoranAsthma OutcomesAsthma SymptomsMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Asthma Risk Pelotas Salvadoran Asthma Outcomes Asthma Symptoms Medicine R Science Q
spellingShingle	Asthma Risk Pelotas Salvadoran Asthma Outcomes Asthma Symptoms Medicine R Science Q 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
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.
format	article
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
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 Portfolio
publishDate	2018
url	https://doaj.org/article/485e978fbba34aad8e8f96a287674be5
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Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America

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