Pasanen Anu, Karjalainen Minna K, Korppi Matti, Hallman Mikko, Rämet Mika
Research Unit of Clinical Medicine, University of Oulu.
Medical Research Center Oulu, Oulu University Hospital and University of Oulu.
J Infect Dis. 2025 Aug 14;232(2):e193-e202. doi: 10.1093/infdis/jiae467.
Acute viral bronchiolitis is a major cause of infant hospitalizations worldwide. Childhood bronchiolitis is considered a risk factor for asthma, suggesting shared genetic factors and biological pathways. Genetic risk loci may provide new insights into disease pathogenesis.
We conducted a genome-wide association study to examine the genetic contributions to bronchiolitis susceptibility in the FinnGen project data. We analyzed 1465 infants hospitalized for bronchiolitis who were <2 years of age and 356 404 individuals without a history of acute lower respiratory infections.
The genome-wide association study identified associations (P < 5 × 10-8) for variants in gasdermin B (GSDMB) and a missense variant in cadherin-related family member 3 (CDHR3). Children with bronchiolitis in infancy were more likely to develop asthma later in life as compared with controls. The 2 associated loci were previously linked to asthma and susceptibility to wheezing illness by causative agents other than respiratory syncytial virus (RSV). The identified loci were associated with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection.
Our results suggest that genetic variants in CDHR3 and GSDMB modulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV. Severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals, or it could be a marker of genetic predisposition to asthma.
急性病毒性细支气管炎是全球范围内婴儿住院的主要原因。儿童细支气管炎被认为是哮喘的一个危险因素，提示存在共同的遗传因素和生物学途径。遗传风险位点可能为疾病发病机制提供新的见解。
我们在芬兰基因计划数据中进行了一项全基因组关联研究，以检查基因对细支气管炎易感性的影响。我们分析了1465名因细支气管炎住院的2岁以下婴儿以及356404名无急性下呼吸道感染病史的个体。
全基因组关联研究确定了gasdermin B（GSDMB）基因变异和钙黏蛋白相关家族成员3（CDHR3）的一个错义变异存在关联（P < 5×10⁻⁸）。与对照组相比，婴儿期患细支气管炎的儿童日后患哮喘的可能性更大。这两个相关位点此前已通过呼吸道合胞病毒（RSV）以外的病原体与哮喘和喘息性疾病易感性相关联。所确定的位点与总体细支气管炎相关，在非RSV感染引起的细支气管炎中作用比RSV感染引起的更大。
我们的结果表明，CDHR3和GSDMB基因变异可调节对细支气管炎的易感性，尤其是由RSV以外的病毒引起的细支气管炎。婴儿期严重的细支气管炎可能会在遗传易感性个体中引发哮喘的发生，或者它可能是哮喘遗传易感性的一个标志。
