Extract
Over the past 12 years, many genome-wide association studies (GWAS) have been conducted to identify susceptibility variants for asthma [1–5]. The Trans-National Asthma Genetic Consortium (TAGC) recently conducted a large meta-analysis of GWAS [3], identifying 878 single nucleotide polymorphisms (SNPs) associated with asthma at 18 loci. The mechanisms underlying such associations are largely unknown but may include effects on gene expression that alter airway epithelial integrity and function.
Abstract
Many asthma-susceptibility SNPs are associated with expression of distant cis-genes in airway epithelium (AE) through DNA methylation. Over 40% of the genes whose expression in AE is associated with such SNPs are differentially expressed in atopic asthma. http://bit.ly/2L1rnIk
Footnotes
Author contributions: W. Chen and J.C. Celedón conceived and designed the study. S. Kim and E. Forno conducted the primary analysis and interpreted data. Q. Yan, Y. Jiang, R. Zhang, N. Boutaoui, E. Acosta-Pérez and G. Canino participated in data collection and data analysis. S. Kim, E. Forno, W. Chen and J.C. Celedón prepared the first draft of the manuscript. All authors reviewed the draft for intellectual content, and approved submission of the final version of the manuscript.
Conflict of interest: S. Kim has nothing to disclose.
Conflict of interest: E. Forno has nothing to disclose.
Conflict of interest: Q. Yan has nothing to disclose.
Conflict of interest: Y. Jiang has nothing to disclose.
Conflict of interest: R. Zhang has nothing to disclose.
Conflict of interest: N. Boutaoui has nothing to disclose.
Conflict of interest: E. Acosta-Pérez has nothing to disclose.
Conflict of interest: G. Canino has nothing to disclose.
Conflict of interest: W. Chen has nothing to disclose.
Conflict of interest: J.C. Celedón has received research materials from GSK and Merck (inhaled steroids) and Pharmavite (vitamin D and Placebo capsules), in order to provide medications free of cost to participants in NIH-funded studies, unrelated to the current work.
Support statement: This study was supported by grants HL079966, HL117191, and MD011764 (PI: J.C. Celedón) from the U.S. National Institutes of Health (NIH). S. Kim is supported by a T32 training grant (HL129949) from the US NIH. E. Forno's contribution was supported by NIH grant HL125666. Funding information for this article has been deposited with the Crossref Funder Registry
- Received August 30, 2019.
- Accepted November 24, 2019.
- Copyright ©ERS 2020