Common genetic variation influencing the human lung imaging phenotypes.
Authors
Affiliations (14)
Affiliations (14)
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
- State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
- Wuxi Medical Center, Nanjing Medical University, Nanjing, China.
- Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
- Department of Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
- Department of Cancer Prevention, Taizhou Cancer Hospital, Taizhou, China.
- Department of Radiology, Taizhou Cancer Hospital, Taizhou, China.
- Department of Health Promotion Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. [email protected].
- State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. [email protected].
- The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China. [email protected].
- Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China. [email protected].
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. [email protected].
- State Key Laboratory Cultivation Base of Biomarkers for Cancer Precision Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. [email protected].
Abstract
Lung structures are critical for gas exchange and contribute to the pathogenesis of respiratory diseases, exhibiting notable lobe-specific heterogeneity. To investigate their genetic basis, we apply a deep-learning AI system and Pyradiomics to define lobe-specific lung CT imaging phenotypes, conducting genome-wide analyses in 35,469 participants from the Lung Imaging Genomics Initiative in China. We identify 36 loci associated with voxel intensities and 138 loci linked to three-dimensional shape. Functional annotation reveals significant enrichment of relevant genes in pathways regulating early fetal lung development and loci enriched in fetal lung regulatory elements. Genetic correlations are identified between lung structures and chronic respiratory diseases as well as lung function, with a number of loci showing colocalization. Mendelian randomization analyses suggest a causal role of lung structures in chronic lung diseases and extrapulmonary traits. This study provides new insights into the genetic architecture of lung structures and their links to diverse clinical outcomes.