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https://www.arca.fiocruz.br/handle/icict/50155
GENOME-WIDE ASSOCIATION STUDY OF ASTHMA, TOTAL IGE, AND LUNG FUNCTION IN A COHORT OF PERUVIAN CHILDREN
Imunoglobulina E
Função Respiratória
Estudo de Associação Genômica Ampla
Peru
Ancestralidade
Alergia
Immunoglobulin E
Lung function
Admixture
Genome wide association analyses
Peru
Ancestry
Allergy
Author
Akenroye, Ayobami T.
Brunetti, Tonya
Romero, Karina
Daya, Michelle
Kanchan, Kanika
Shankar, Gautam
Chavan, Sameer
Boorgula, Meher Preethi
Ampleford, Elizabeth A.
Fonseca, Hellen Freitas
Hawkins, Gregory A.
Teixeira, Helena Mariana Pitangueira
Campbell, Monica
Rafaels, Nicholas
Winters, Alexandra
Bleecker, Eugene R.
Cruz, Alvaro A.
Barreto, Mauricio Lima
Meyers, Deborah A.
Ortega, Victor E.
Figueiredo, Camila A.
Barnes, Kathleen C.
Checkley, William
Hansel, Nadia N.
Mathias, Rasika A.
Brunetti, Tonya
Romero, Karina
Daya, Michelle
Kanchan, Kanika
Shankar, Gautam
Chavan, Sameer
Boorgula, Meher Preethi
Ampleford, Elizabeth A.
Fonseca, Hellen Freitas
Hawkins, Gregory A.
Teixeira, Helena Mariana Pitangueira
Campbell, Monica
Rafaels, Nicholas
Winters, Alexandra
Bleecker, Eugene R.
Cruz, Alvaro A.
Barreto, Mauricio Lima
Meyers, Deborah A.
Ortega, Victor E.
Figueiredo, Camila A.
Barnes, Kathleen C.
Checkley, William
Hansel, Nadia N.
Mathias, Rasika A.
Affilliation
"Múltipla ver em Notas"
Abstract
Background: Genetic ancestry plays a role in asthma health
disparities.
Objective: Our aim was to evaluate the impact of ancestry on
and identify genetic variants associated with asthma, total
serum IgE level, and lung function.
Methods: A total of 436 Peruvian children (aged 9-19 years)
with asthma and 291 without asthma were genotyped by using
the Illumina Multi-Ethnic Global Array. Genome-wide
proportions of indigenous ancestry populations from
continental America (NAT) and European ancestry from the
Iberian populations in Spain (IBS) were estimated by using
ADMIXTURE. We assessed the relationship between ancestry
and the phenotypes and performed a genome-wide association
study.
Results: The mean ancestry proportions were 84.7% NAT (case
patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%;
14.6%). With adjustment for asthma, NAT was associated with
higher total serum IgE levels (P < .001) and IBS was associated
with lower total serum IgE levels (P < .001). NAT was associated
with higher FEV1 percent predicted values (P < .001), whereas
IBS was associated with lower FEV1 values in the controls but
not in the case patients. The HLA-DR/DQ region on
chromosome 6 (Chr6) was strongly associated with total serum
IgE (rs3135348; P 5 3.438 3 10–10) and was independent of an
association with the haplotype HLA-DQA1 HLADQB1:
04.01 04.02 (P 5 1.55 3 10–05). For lung function, we
identified a locus (rs4410198; P 5 5.536 3 10–11) mapping to
Chr19, near a cluster of zinc finger interacting genes that
colocalizes to the long noncoding RNA CTD-2537I9.5. This novel
locus was replicated in an independent sample of pediatric case
patients with asthma with similar admixture from Brazil (P 5
.005).
Conclusion: This study confirms the role of HLA in atopy, and
identifies a novel locus mapping to a long noncoding RNA for
lung function that may be specific to children with NAT.
Keywords in Portuguese
AsmaImunoglobulina E
Função Respiratória
Estudo de Associação Genômica Ampla
Peru
Ancestralidade
Alergia
Keywords
AsthmaImmunoglobulin E
Lung function
Admixture
Genome wide association analyses
Peru
Ancestry
Allergy
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