COPDの遺伝は若年者の肺機能に重要である(Genetics of COPD important for lung function in young people)

2024-08-14

2024-08-13 カロリンスカ研究所(KI)

カロリンスカ研究所とヨーロッパの15の研究センターが行った研究によれば、COPD(慢性閉塞性肺疾患)に関連する遺伝子変異が、子供や青年期の肺機能低下にも影響を与えることが判明しました。この発見により、COPDが幼少期から始まる可能性が示され、早期予防の重要性が強調されています。研究者たちは、COPD発症リスクが高い人々を特定し、予防策を講じることを目指しています。

<関連情報>

生涯にわたる肺機能における気流制限の遺伝学的研究-多遺伝子リスクスコア研究 Exploring the genetics of airflow limitation in lung function across the lifespan – a polygenic risk score study

Natalia Hernandez-Pacheco,Anna Kilanowski,Ashish Kumar,John A. Curtin,Núria Olvera,Sara Kress,et al.
eClinicalMedicine Published:August 12, 2024
DOI:https://doi.org/10.1016/j.eclinm.2024.102731

Summary

Background
Chronic obstructive pulmonary disease (COPD) is caused by interactions between many factors across the life course, including genetics. A proportion of COPD may be due to reduced lung growth in childhood. We hypothesized that a polygenic risk score (PRS) for COPD is associated with lower lung function already in childhood and up to adulthood.

Methods
A weighted PRS was calculated based on the 82 association signals (p ≤ 5 × 10^-8) revealed by the largest GWAS of airflow limitation (defined as COPD) to date. This PRS was tested in association with lung function measures (FEV₁, FVC, and FEV₁/FVC) in subjects aged 4–50 years from 16 independent cohorts participating in the Chronic Airway Diseases Early Stratification (CADSET) Clinical Research Collaboration. Age-stratified meta-analyses were conducted combining the results from each cohort (n = 45,406). These findings were validated in subjects >50 years old.

Findings
We found significant associations between the PRS for airflow limitation and: (1) lower pre-bronchodilator FEV₁/FVC from school age (7–10 years; β: -0.13 z-scores per one PRS z-score increase [–0.15, -0.11], q-value = 7.04 × 10^-53) to adulthood (41–50 years; β: -0.16 [–0.19, -0.13], q-value = 1.31 × 10^-24); and (2) lower FEV₁ (from school age: 7–10 years; β: -0.07 [–0.09, -0.05], q-value = 1.65 × 10^-9, to adulthood: 41–50 years; β: -0.17 [–0.20, -0.13], q-value = 4.48 x 10^-20). No effect modification by smoking, sex, or a diagnosis of asthma was observed.