Voorhies Kirsten, Sordillo Joanne E, McGeachie Michael, Ampleford Elizabeth, Wang Alberta L, Lasky-Su Jessica, Tantisira Kelan, Dahlin Amber, Kelly Rachel S, Ortega Victor E, Lutz Sharon M, Wu Ann C
Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA 02215, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Pers Med. 2021 Jan 19;11(1):59. doi: 10.3390/jpm11010059.
An unaddressed and important issue is the role age plays in modulating response to short acting β2-agonists in individuals with asthma. The objective of this study was to identify whether age modifies genetic associations of single nucleotide polymorphisms (SNPs) with bronchodilator response (BDR) to β2-agonists. Using three cohorts with a total of 892 subjects, we ran a genome wide interaction study (GWIS) for each cohort to examine SNP by age interactions with BDR. A fixed effect meta-analysis was used to combine the results. In order to determine if previously identified BDR SNPs had an age interaction, we also examined 16 polymorphisms in candidate genes from two published genome wide association studies (GWAS) of BDR. There were no significant SNP by age interactions on BDR using the genome wide significance level of 5 × 10. Using a suggestive significance level of 5 × 10, three interactions, including one for a SNP within (rs4840337), were significant and replicated at the significance level of 0.05. Considering candidate genes from two previous GWAS of BDR, three SNPs (rs10476900 (near ) [-value = 0.009], rs10827492 () [-value = 0.02], and rs72646209 () [-value = 0.02]) had a marginally significant interaction with age on BDR ( < 0.05). Our results suggest age may be an important modifier of genetic associations for BDR in asthma.
一个尚未解决的重要问题是年龄在调节哮喘患者对短效β2激动剂反应中所起的作用。本研究的目的是确定年龄是否会改变单核苷酸多态性（SNP）与β2激动剂支气管扩张反应（BDR）之间的遗传关联。我们使用了三个队列，共892名受试者，对每个队列进行全基因组相互作用研究（GWIS），以检验SNP与年龄对BDR的相互作用。采用固定效应荟萃分析来合并结果。为了确定先前鉴定的BDR SNP是否存在年龄相互作用，我们还研究了来自两项已发表的BDR全基因组关联研究（GWAS）中候选基因的16个多态性。使用5×10的全基因组显著性水平，未发现SNP与年龄对BDR有显著的相互作用。使用5×10的提示性显著性水平，三个相互作用，包括一个位于（rs4840337）内的SNP的相互作用，在0.05的显著性水平上具有显著性且可重复。考虑到先前两项BDR GWAS中的候选基因，三个SNP（rs10476900（靠近）[-值 = 0.009]、rs10827492（）[-值 = 0.02]和rs72646209（）[-值 = 0.02]）与年龄对BDR有边缘显著的相互作用（<0.05）。我们的结果表明，年龄可能是哮喘中BDR遗传关联的重要调节因素。
