Exome sequencing identifies novel genetic variants associated with varicose veins.

Autor: Zhang DD; Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China., He XY; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China., Yang L; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China., Wu BS; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China., Fu Y; Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China., Liu WS; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China., Guo Y; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China., Fei CJ; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China., Kang JJ; Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China., Feng JF; Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.; Department of Computer Science, University of Warwick, Coventry, United Kingdom., Cheng W; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.; Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai, China.; Department of Computer Science, University of Warwick, Coventry, United Kingdom., Tan L; Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China., Yu JT; Department of Neurology and National Center for Neurological Disorders, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2024 Jul 09; Vol. 20 (7), pp. e1011339. Date of Electronic Publication: 2024 Jul 09 (Print Publication: 2024).
DOI: 10.1371/journal.pgen.1011339
Abstrakt: Background: Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood.
Methods: We conducted an exome-wide association study of VV using whole-exome sequencing data from the UK Biobank, and focused on common and rare variants using single-variant association analysis and gene-level collapsing analysis.
Findings: A total of 13,823,269 autosomal genetic variants were obtained after quality control. We identified 36 VV-related independent common variants mapping to 34 genes by single-variant analysis and three rare variant genes (PIEZO1, ECE1, FBLN7) by collapsing analysis, and most associations between genes and VV were replicated in FinnGen. PIEZO1 was the closest gene associated with VV (P = 5.05 × 10-31), and it was found to reach exome-wide significance in both single-variant and collapsing analyses. Two novel rare variant genes (ECE1 and METTL21A) associated with VV were identified, of which METTL21A was associated only with females. The pleiotropic effects of VV-related genes suggested that body size, inflammation, and pulmonary function are strongly associated with the development of VV.
Conclusions: Our findings highlight the importance of causal genes for VV and provide new directions for treatment.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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