Common genetic variation influencing the human lung imaging phenotypes
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.
Authors
- Hongbing Shen (ORCID: https://orcid.org/0000-0002-2581-5906)
- Lingbin Du (ORCID: https://orcid.org/0000-0002-1992-7784)
- Hongxia Ma (ORCID: https://orcid.org/0000-0002-9821-6955)
- Lei Shi (ORCID: https://orcid.org/0000-0003-0031-2808)
- Jin Chen (ORCID: https://orcid.org/0000-0002-5557-2079)
- Meng Zhu (ORCID: https://orcid.org/0000-0003-4338-2566)
- Yuanlin Mou (ORCID: https://orcid.org/0000-0003-4117-9660)
- Fei‐Yun Wu (ORCID: https://orcid.org/0000-0002-0276-4093)
- Guangfu Jin (ORCID: https://orcid.org/0000-0003-0249-5337)
- Yue Jiang (ORCID: https://orcid.org/0009-0000-9945-6937)
- Chen Zhu (ORCID: https://orcid.org/0000-0001-5302-1233)
- Linnan Gong
- Juncheng Dai (ORCID: https://orcid.org/0000-0002-3909-5671)
- Lingying Zhu (ORCID: https://orcid.org/0009-0003-8253-868X)
- Dong Hang (ORCID: https://orcid.org/0000-0001-6944-0459)
- Ji Chen
- Yating Fu (ORCID: https://orcid.org/0009-0009-0278-4594)
- Ci Song (ORCID: https://orcid.org/0000-0001-6483-9372)
- Zhibin Hu (ORCID: https://orcid.org/0000-0002-8277-5234)
- Jing Lü (ORCID: https://orcid.org/0000-0001-6017-326X)
- Qun Zhang (ORCID: https://orcid.org/0000-0002-5792-4517)
- Cheng Zhang (ORCID: https://orcid.org/0000-0001-5317-8775)
- Jiahao Zhang (ORCID: https://orcid.org/0000-0001-9421-2415)
- Xiangdong Cheng (ORCID: https://orcid.org/0000-0003-1470-2831)
- Jiaying Cai
- Mingxuan Zhu
- Lili Wu (ORCID: https://orcid.org/0000-0002-9515-4533)
- Qiao Li
Institutions
- Sun Yat-sen University (CN)
- Chinese Academy of Sciences (CN)
- Wenzhou Medical University (CN)
- Zhejiang Cancer Hospital (CN)
- Taizhou Central Hospital (CN)
- Sun Yat-sen University Cancer Center (CN)
- Changzhou No.2 People's Hospital (CN)
- Wuxi People's Hospital (CN)
- Zhejiang Taizhou Hospital (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1038/s41467-025-64571-z
- Citations
- 1
- Primary Topic
- Congenital Diaphragmatic Hernia Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- National Natural Science Foundation of China
- Nanjing Medical University
- National Science and Technology Major Project