RT Journal Article
SR Electronic
T1 Admixture mapping of severe asthma exacerbations in Hispanic/Latino children and youth
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 233
OP 241
DO 10.1136/thorax-2022-218755
VO 78
IS 3
A1 Herrera-Luis, Esther
A1 Mak, Angel C Y
A1 Perez-Garcia, Javier
A1 Martin-Gonzalez, Elena
A1 Eng, Celeste
A1 Beckman, Kenneth B
A1 Huntsman, Scott
A1 Hu, Donglei
A1 González-Pérez, Ruperto
A1 Hernández-Pérez, José M
A1 Mederos-Luis, Elena
A1 Sio, Yang Yie
A1 Poza-Guedes, Paloma
A1 Sardón, Olaia
A1 Corcuera, Paula
A1 Sánchez-Machín, Inmaculada
A1 Korta-Murua, Javier
A1 Martínez-Rivera, Carlos
A1 Mullol, Joaquim
A1 Muñoz, Xavier
A1 Valero, Antonio
A1 Sastre, Joaquin
A1 Garcia-Aymerich, Judith
A1 Llop, Sabrina
A1 Torrent, Maties
A1 Casas, Maribel
A1 Rodríguez-Santana, José R
A1 Villar, Jesús
A1 del Pozo, Victoria
A1 Lorenzo-Diaz, Fabian
A1 Williams, L Keoki
A1 Melén, Erik
A1 Chew, Fook Tim
A1 Borrell, Luisa N
A1 Burchard, Esteban G
A1 Pino-Yanes, Maria
YR 2023
UL http://thorax.bmj.com/content/78/3/233.abstract
AB Background In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations.Objective We sought to identify genetic variants associated with severe asthma exacerbations in Hispanic/Latino subgroups by means of admixture mapping analyses and fine mapping, and to assess their transferability to other populations and potential functional roles.Methods We performed an admixture mapping in 1124 Puerto Rican and 625 Mexican American children with asthma. Fine-mapping of the significant peaks was performed via allelic testing of common and rare variants. We performed replication across Hispanic/Latino subgroups, and the transferability to non-Hispanic/Latino populations was assessed in 1001 African Americans, 1250 Singaporeans and 941 Europeans with asthma. The effects of the variants on gene expression and DNA methylation from whole blood were also evaluated in participants with asthma and in silico with data obtained through public databases.Results Genomewide significant associations of Indigenous American ancestry with severe asthma exacerbations were found at 5q32 in Mexican Americans as well as at 13q13-q13.2 and 3p13 in Puerto Ricans. The single nucleotide polymorphism (SNP) rs1144986 (C5orf46) showed consistent effects for severe asthma exacerbations across Hispanic/Latino subgroups, but it was not validated in non-Hispanics/Latinos. This SNP was associated with DPYSL3 DNA methylation and SCGB3A2 gene expression levels.Conclusions Admixture mapping study of asthma exacerbations revealed a novel locus that exhibited Hispanic/Latino-specific effects and regulated DPYSL3 and SCGB3A2.All data relevant to the study are included in the article or uploaded as supplementary information. TOPMed WGS and RNA-seq data from GALA II are available on dbGaP under accession number phs000920.v4.p2. TOPMed WGS data from SAGE is available on dbGaP under accession number phs000921.v4.p1.