Van Asselt Austin J, Pool René, Hottenga Jouke-Jan, Beck Jeffrey J, Finnicum Casey T, Johnson Brandon N, Kallsen Noah, Viet Sarah, Huizenga Patricia, de Geus Eco, Boomsma Dorret I, Ehli Erik A, van Dongen Jenny
Avera McKennan Hospital & University Health Center, Sioux Falls, SD 57105, USA.
Department of Biological Psychology, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands.
Biomolecules. 2025 Feb 8;15(2):251. doi: 10.3390/biom15020251.
Asthma, a chronic respiratory condition characterized by airway inflammation, affects millions of individuals worldwide. Challenges remain in asthma prediction and diagnosis from its complex etiology involving genetic and environmental factors. Here, we investigated the relationship between genome-wide DNA methylation and genetic risk for asthma quantified via polygenic scores in two cohorts from the Netherlands Twin Register; one enriched with asthmatic families measured on the Illumina EPIC array (n = 526) and a general population cohort measured on the Illumina HM450K array (n = 2680). We performed epigenome-wide association studies of asthma polygenic scores in each cohort with results combined through meta-analysis (total samples = 3206). The EWAS meta-analysis identified 63 significantly associated CpGs, (following Bonferroni correction, α = 0.05/358,316). An investigation of previous mQTL associations identified 48 mQTL associations between 24 unique CpGs and 48 SNPs, of which two SNPs have previous associations with asthma. Enrichment analysis using the 63 significant CpGs highlighted previous associations with ancestry, smoking, and air pollution. A dizygotic twin within-pair analysis of the 63 CpGs revealed similar directional effects between the two cohorts in 33 of the 63 CpGs. These findings further characterize the intricate relationship between DNA methylation and genetics relative to asthma.
哮喘是一种以气道炎症为特征的慢性呼吸系统疾病，全球有数百万人受其影响。由于哮喘的病因复杂，涉及遗传和环境因素，其预测和诊断仍面临挑战。在此，我们在荷兰双胞胎登记处的两个队列中，研究了全基因组DNA甲基化与通过多基因评分量化的哮喘遗传风险之间的关系；一个队列是在Illumina EPIC阵列上测量的富含哮喘家族的队列（n = 526），另一个是在Illumina HM450K阵列上测量的普通人群队列（n = 2680）。我们在每个队列中进行了哮喘多基因评分的表观基因组全关联研究，并通过荟萃分析合并结果（总样本数 = 3206）。表观基因组全关联研究荟萃分析确定了63个显著相关的CpG（经Bonferroni校正后，α = 0.05/358,316）。对先前mQTL关联的调查确定了24个独特CpG与48个SNP之间的48个mQTL关联，其中两个SNP先前与哮喘有关联。使用这63个显著CpG进行的富集分析突出了先前与祖先、吸烟和空气污染的关联。对这63个CpG进行的异卵双胞胎配对内分析显示，在63个CpG中的33个中，两个队列之间存在相似的方向性效应。这些发现进一步描述了DNA甲基化与哮喘相关遗传学之间的复杂关系。
