The Lancet regional health. Europe · 2026
Infant respiratory syncytial virus and childhood asthma: a nationwide registry-based, sibling-controlled, and genome-wide association study.
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Vartiainen Pekka, Haapaniemi Hele, Lee Yunsung, Magnus Maria C, Hartonen Tuomo, Detrois Kira, Viippola Essi, Ferro Matteo, Laitinen Tarja, FinnGen, Madsen Maiken A, Ostrowski Sisse R, Pedersen Ole B, Sørensen Erik, Erikstrup Christian, Gong Tong, Rhedin Samuel, Lundholm Cecilia, Dallagiacoma Giulia, Almqvist Catarina, Egeskov-Cavling Amanda M, Fischer Thea K, Pasanen Anu, Rämet Mika, Vuorinen Anna-Leena, Hiekkalinna Tero, Håberg Siri E, Magnus Per, Perola Markus, Jugessur Astanand, Ganna Andrea, Heinonen Santtu
Аннотация
BACKGROUND: Early-life respiratory syncytial virus (RSV) infection is associated with childhood recurrent wheeze or asthma (RW/A), but causality and shared genetic liability remain unclear.
METHODS: We combined Finnish nationwide registries and Nordic genetic cohorts. First, in 965,312 Finnish children born between 1998 and 2014, we defined severe RSV as RSV hospitalisation before age 1 year, and recurrent wheezing or asthma (RW/A) as inhaled medication reimbursement between ages 1 and 7 years, and compared medication and eosinophil trajectories by RSV history. Second, we assessed familial confounding in 527,776 full siblings and 15,667 RW/A-discordant pairs. Third, we performed a genome-wide association study (GWAS) of RSV susceptibility with meta-analysis across six Nordic cohorts (3107 cases, 92,091 controls) and two-sample Mendelian randomisation (MR) using 155 asthma-associated variants.
FINDINGS: RSV-associated RW/A showed higher inhaled medication use at ages 1-2 years but lower use after age 5, and lower mean blood eosinophils (0.341 vs. 0.398 × 109/L; p = 0.008) than RW/A without RSV hospitalisation. In RW/A-discordant sibling pairs, RSV hospitalisation was associated with RW/A (OR 2.8; 95% CI 2.4-3.2), while unaffected siblings also had elevated RW/A prevalence. GWAS identified an RSV association at APBB1IP (rs787036; β = 0.209; p = 8.80 × 10-9). Two-sample MR provided no evidence that asthma genetic liability influenced RSV susceptibility.
INTERPRETATION: The RSV-asthma association is unlikely to be explained by shared genetic or environmental factors, and RSV-associated RW/A shows a distinct trajectory. These findings help prioritise long-term outcomes for RSV prevention trials and monitoring.
FUNDING: Päivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Orion Research Foundation, the Research Council of Norway.
METHODS: We combined Finnish nationwide registries and Nordic genetic cohorts. First, in 965,312 Finnish children born between 1998 and 2014, we defined severe RSV as RSV hospitalisation before age 1 year, and recurrent wheezing or asthma (RW/A) as inhaled medication reimbursement between ages 1 and 7 years, and compared medication and eosinophil trajectories by RSV history. Second, we assessed familial confounding in 527,776 full siblings and 15,667 RW/A-discordant pairs. Third, we performed a genome-wide association study (GWAS) of RSV susceptibility with meta-analysis across six Nordic cohorts (3107 cases, 92,091 controls) and two-sample Mendelian randomisation (MR) using 155 asthma-associated variants.
FINDINGS: RSV-associated RW/A showed higher inhaled medication use at ages 1-2 years but lower use after age 5, and lower mean blood eosinophils (0.341 vs. 0.398 × 109/L; p = 0.008) than RW/A without RSV hospitalisation. In RW/A-discordant sibling pairs, RSV hospitalisation was associated with RW/A (OR 2.8; 95% CI 2.4-3.2), while unaffected siblings also had elevated RW/A prevalence. GWAS identified an RSV association at APBB1IP (rs787036; β = 0.209; p = 8.80 × 10-9). Two-sample MR provided no evidence that asthma genetic liability influenced RSV susceptibility.
INTERPRETATION: The RSV-asthma association is unlikely to be explained by shared genetic or environmental factors, and RSV-associated RW/A shows a distinct trajectory. These findings help prioritise long-term outcomes for RSV prevention trials and monitoring.
FUNDING: Päivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Orion Research Foundation, the Research Council of Norway.