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Identification of DNA methylation markers associated with lung function in Latino youth with asthma

Authors
Esther Herrera-Luis†, Annie Li†, Angel C. Y. Mak, Javier Perez-Garcia, Jennifer R. Elhawary, Sam S. Oh, PhD, Donglei Hu, Celeste Eng, Kevin L. Keys, Scott Huntsman, Kennenth B. Beckman, Luisa N. Borell, Jose Rodriguez-Santana, Esteban G. Burchard†, Maria Pino-Yanes, PhD† († equal contribution)
Name and Date of Professional Meeting
EAACI Pediatric Allergy and Asthma Meeting (PAAM), 12–13 November 2021
Associated paper proposal(s)
Working Group(s)
Abstract Text
Introduction: Lung function, a key health indicator in respiratory illnesses, is influenced by numerous environmental exposures and genetic ancestry, which vary by race/ethnicity. Despite this, the role of the DNA methylome on lung function has been investigated primarily in European-descent adults. Here, we aimed to identify DNA methylation loci associated with lung function in Latino youth with asthma and validate previous epigenetic signals from non-Latino populations.

Methods: We performed several epigenome-wide association studies of lung function measurements analyzing whole blood from 247 Puerto Rican and 148 Mexican American youth with asthma. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and their pre- and post- albuterol administration ratio were evaluated. The effects of genetic variation on DNA methylation were investigated for the genome-wide significant (p=1.17x10-7) CpG sites identified. Differentially methylated regions and enrichment analyses in previous EWAS associations were also conducted.

Results: Three CpGs were genome-wide significantly associated with lung function in Latinos: cg14441538 near PRKG1-AS1 showed significant association with pre-bronchodilator FVC (p=7.69x10-10), cg00914963 near TBC1D16 was associated with post-bronchodilator FVC (p=5.14x10-8), and cg20515679 near KCNJ6 with post-bronchodilator FEV1/FVC (p=7.21x10-8). DNA methylation at cg00914963 was genetically regulated in Latinos. Additionally, two differentially methylated regions at LY6G5C and AURKC were associated with pre-bronchodilator lung function (adjusted p<0.05) in Puerto Ricans and Mexican Americans. Moreover, some of the epigenetics marks previously associated with lung function in non-Latino populations were replicated. Furthermore, there was significant enrichment (p<0.05) in previous EWAS signals for known lung health-related factors, such as respiratory diseases, smoking, or preterm birth.

Conclusions: We uncovered novel epigenetic markers associated with lung function in Puerto Ricans and Mexican Americans and validated associations previously described in non-Latino populations.
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