Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland.
Virology Unit, Institute of Biomedicine, University of Turku, Turku, Finland.
J Infect Dis. 2023 Oct 18;228(8):990-998. doi: 10.1093/infdis/jiad075.
Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in early childhood is unclear.
We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 preselected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies.
The asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01-1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01-1.20, P = .03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses.
Asthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors. Clinical Trials Registration. NCT00494624 and NCT00731575.
全基因组关联研究已经确定了几个儿童早期哮喘的风险等位基因，特别是在 17q21 基因座和钙黏蛋白相关家族成员 3（CDHR3）基因中。这些等位基因对儿童早期急性呼吸道感染（ARI）风险的贡献尚不清楚。
我们分析了未选择儿童的 STEPS 出生队列研究以及严重喘息性疾病儿童的 VINKU 和 VINKU2 研究的数据。对 1011 名儿童进行了全基因组基因分型。我们分析了 11 个预先选择的哮喘风险等位基因与各种病毒病因的 ARI 和喘息性疾病风险之间的关联。
CDHR3、GSDMA 和 GSDMB 中的哮喘风险等位基因与 ARI 发生率增加相关（对于 CDHR3，发病率比[IRR]，1.06；95%置信区间[CI]，1.01-1.12；P =.02），CDHR3 基因中的风险等位基因与鼻病毒感染相关（IRR，1.10；95%CI，1.01-1.20，P =.03）。GSDMA、GSDMB、IKZF3、ZPBP2 和 ORMDL3 基因中的哮喘风险等位基因与儿童早期喘息性疾病相关，尤其是鼻病毒阳性喘息性疾病。
哮喘风险等位基因与 ARI 发生率增加和病毒性喘息性疾病风险增加相关。非喘息性和喘息性 ARI 和哮喘可能具有共同的遗传风险因素。临床试验注册。NCT00494624 和 NCT00731575。
