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

Autor:	Nissen, Gyde, Hinsenbrock, Svenja, Rausch, Tanja K., Stichtenoth, Guido, Ricklefs, Isabell, Weckmann, Markus, Franke, Andre, Herting, Egbert, König, Inke R., Kopp, Matthias V., Rabe, Klaus F., Göpel, Wolfgang
Předmět:	RISK factors of environmental exposure PREMATURE infant diseases SINGLE nucleotide polymorphisms REGRESSION analysis RISK assessment VITAL capacity (Respiration) BRONCHITIS OBSTRUCTIVE lung diseases PULMONARY function tests FORCED expiratory volume GENETIC profile DISEASE risk factors DISEASE complications ADULTS
Zdroj:	NEJM Evidence; Mar2023, Vol. 2 Issue 3, p1-10, 10p
Abstrakt:	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.) Polygenic risk score (PRS) for FEV1 and FVC was calculated in children born prematurely. 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 at highest risk had lower lung function by these measures and higher rates of obstructive bronchitis. [ABSTRACT FROM AUTHOR]
Databáze:	Supplemental Index
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