Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis |
| |
| Authors: | Juan Liu Zheng Wang Yanyan Cao Yong Mou Bohua Fu Biwen Mo Jianghong Wei Zhenshun Cheng Liman Luo Jingping Li Ying Shu Xiaomei Wang Guangwei Luo Shuo Yang Yingnan Wang Jing Zhu Jingping Yang Ming Wu Xuyan Xu Renying Ge Xueqin Chen Qingzhen Peng Guang Wei Yaqing Li Hua Yang Shirong Fang Xiaoju Zhang Weining Xiong |
| |
| Affiliation: | 1. Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Key Cite of National Clinical Research Center for Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China;2. Department of Respiratory Medicine, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, China;3. Division of Cardiology, Departments of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;4. Department of Respiratory Medicine, Affiliated hospital of Guilin Medical University, Guilin, China;5. Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China;6. Department of Pediatrics, The 306 Hospital of People's Liberation Army, Beijing, China;7. Department of Respiratory Medicine, Qianjiang Central Hospital, Qianjiang, China;8. Department of Geriatrics, Southwest Hospital, Army Medical University, Chongqing, China;9. Department of Respiratory Medicine, Wuhan No. 1 Hospital, Wuhan, China;10. Department of Respiratory and Critical Care Medicine, Renmin Hospital of Three Gorges University, Yichang, China;11. Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Inner Mongolia Medical University, Baotou, China;12. Department of Respiratory Medicine, Xianning Center Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China;13. Department of Respiratory and Critical Care Medicine, Wuhan University Renmin Hospital, Wuhan University, Wuhan, China;14. Department of Respiratory Medicine, Xiaogan Central Hospital, Xiaogan, China;15. Department of Respiratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, China;16. Department of Respiratory Medicine, University Hospital of Hubei University for Nationalities, Enshi, China |
| |
| Abstract: | Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (～80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF‐related genes were selected and sequenced in genomic DNAs from 253 sporadic IPF patients and 125 matched health controls using targeted massively parallel next‐generation sequencing. The identified risk variants were confirmed by Sanger sequencing. We identified two pathogenic and 10 loss‐of‐function (LOF) candidate variants, accounting for 4.74% (12 out of 253) of all the IPF cases. In burden tests, rare missense variants in three genes (CSF3R, DSP, and LAMA3) were identified that have a statistically significant relationship with IPF. Four common SNPs (rs3737002, rs2296160, rs1800470, and rs35705950) were observed to be statistically associated with increased risk of IPF. In the cumulative risk model, high risk subjects had 3.47‐fold (95%CI: 2.07–5.81, P = 2.34 × 10?6) risk of developing IPF compared with low risk subjects. We drafted a comprehensive map of genetic risks (including both rare and common candidate variants) in patients with IPF, which could provide insights to help in understanding mechanisms, providing genetic diagnosis, and predicting risk for IPF. |
| |
| Keywords: | common SNP genetic factors idiopathic pulmonary fibrosis next‐generation sequencing risk stratification |
|
|
