Lung Function of Preterm Children Parsed by a Polygenic Risk Score for Adult COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) in adults is a result of environmental risk factors and genetic factors. Polygenic COPD risk scores are highly predictive for lung function in adults. We hypothesized that a polygenic COPD risk score is also predictive for lung function in children who are born preterm. METHODS: Infants with a birth weight of less than 1500 g (n=17,394) were enrolled in the German Neonatal Network. Among these children, we included those with chip genotyping and 5-year follow-up assessment (n=1957) in this analysis. A polygenic COPD risk score derived in adults with COPD was calculated on the basis of 1,637,882 single-nucleotide polymorphisms associated with forced expiratory volume within 1 second (FEV1) and 1,179,331 single-nucleotide polymorphisms associated with FEV1/FVC (forced vital capacity). This score was related to FEV1, FVC, and FEV1/FVC z scores by linear regression analysis. RESULTS: At a mean age at follow-up of 5.8±0.4 years, the polygenic COPD risk score was strongly associated with FEV1 (−0.05 z score/decile, P=6.5 × 10−9) and FEV1/FVC (−0.07 z score/decile, P=4.4 × 10−11) but not FVC. Children in the 10th decile of the polygenic COPD risk score — that is, those at the highest risk — had a mean FEV1 z score of −1.74 (±1.1), indicating lower lung function by these measures and higher rates of obstructive bronchitis. CONCLUSIONS: The upper deciles of a polygenic COPD risk score derived in adults identified a subgroup of children who were born preterm and who are at high risk for obstructive pulmonary disease of prematurity. This finding supports the notion that COPD-associated genes strongly impact lung function in premature children. (Funded by the German Federal Ministry of Education and Research.)