Abstract
Background: The association between lower adult lung function and cardiovascular comorbidities has not been adequately explained and may partly reflect the perturbation of shared developmental pathways.
Aims: We investigated whether 55 lung development genes, associated with adult lung function (Portas et al., Am J Respir Crit Care Med 2020;202:853-65), are also associated with cardiovascular traits.
Methods: In UK Biobank we used colocalisation analysis to determine whether variants in the 55 lung development genes were shared between lung function (FVC or FEV1/FVC) (N=306,476) and blood pressure traits (N=369,905), coronary artery disease (CAD) or carotid intima-media thickness (CIMT) (N=38,469). For CAD we meta-analysed UK Biobank and CARDIoGRAM data to increase statistical power (N=80,095 cases and 509,780 controls).
Results: Of the 55 genes of interest, 18 were shared between lung function and cardiovascular traits, 5 of which were novel for cardiovascular traits (HOXB4, KAT8, MMP24, CSNK2B and SERPING1). The same variant was shared for three of these novel genes, namely KAT8 rs138259061 (FVC with blood pressure/hypertension), MMP24 rs7280 (FVC with pulse pressure, CAD and CIMT), and SERPING1 rs11229063 (FEV1/FVC with pulse pressure), and for TNS1 rs2571445 (FEV1/FVC with blood pressure and CAD). With the exception of SERPING1 rs11229063, the direction of effect was consistent with our hypothesis that lower lung function is associated with increased cardiovascular risk.
Conclusions: Shared developmental signalling pathways may partly explain the observed association of adult lung function with cardiovascular traits, and their investigation identified novel cardiovascular genetic variants.
Footnotes
Cite this article as Eur Respir J 2022; 60: Suppl. 66, 2326.
This article was presented at the 2022 ERS International Congress, in session “-”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022