Nature Communications (Feb 2024)
Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine
- Sen Zhao,
- Hengqiang Zhao,
- Lina Zhao,
- Xi Cheng,
- Zhifa Zheng,
- Mengfan Wu,
- Wen Wen,
- Shengru Wang,
- Zixiang Zhou,
- Haibo Xie,
- Dengfeng Ruan,
- Qing Li,
- Xinquan Liu,
- Chengzhu Ou,
- Guozhuang Li,
- Zhengye Zhao,
- Guilin Chen,
- Yuchen Niu,
- Xiangjie Yin,
- Yuhong Hu,
- Xiaochen Zhang,
- Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study,
- Pengfei Liu,
- Guixing Qiu,
- Wanlu Liu,
- Chengtian Zhao,
- Zhihong Wu,
- Jianguo Zhang,
- Nan Wu
Affiliations
- Sen Zhao
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Hengqiang Zhao
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Lina Zhao
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Xi Cheng
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Zhifa Zheng
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Mengfan Wu
- Institute of Evolution & Marine Biodiversity, College of Marine Life Science, Ocean University of China
- Wen Wen
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Shengru Wang
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Zixiang Zhou
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Haibo Xie
- Institute of Evolution & Marine Biodiversity, College of Marine Life Science, Ocean University of China
- Dengfeng Ruan
- Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, International Campus, Zhejiang University
- Qing Li
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Xinquan Liu
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Chengzhu Ou
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Guozhuang Li
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Zhengye Zhao
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Guilin Chen
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Yuchen Niu
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Xiangjie Yin
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Yuhong Hu
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Xiaochen Zhang
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study
- Pengfei Liu
- Department of Molecular and Human Genetics, Baylor College of Medicine
- Guixing Qiu
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Wanlu Liu
- Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, International Campus, Zhejiang University
- Chengtian Zhao
- Institute of Evolution & Marine Biodiversity, College of Marine Life Science, Ocean University of China
- Zhihong Wu
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Jianguo Zhang
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- Nan Wu
- Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences
- DOI
- https://doi.org/10.1038/s41467-024-45442-5
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 9
Abstract
Abstract Congenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.
