Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America.
Pablo OliveiraGustavo Nunes de Oliveira CostaAndresa K A DamascenoFernando Pires HartwigGeorge C G BarbosaCamila A FigueiredoRita de C Ribeiro-SilvaAlexandre PereiraM Fernanda Lima-CostaFernanda S KehdyEduardo Tarazona-SantosBernardo Lessa HortaLaura C RodriguesRosemeire L FiacconeMaurício Lima BarretoPublished in: Scientific reports (2018)
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.
Keyphrases
- genome wide
- copy number
- chronic obstructive pulmonary disease
- lung function
- young adults
- dna methylation
- mitochondrial dna
- allergic rhinitis
- end stage renal disease
- transcription factor
- chronic kidney disease
- gene expression
- ejection fraction
- oxidative stress
- cell death
- signaling pathway
- physical activity
- peritoneal dialysis
- newly diagnosed
- molecular docking
- electronic health record
- deep learning
- african american
- pi k akt
- patient reported outcomes
- patient reported