Exome sequencing identifies novel genetic variants associated with varicose veins.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
Jul 2024
Jul 2024
Historique:
received:
30
09
2023
accepted:
13
06
2024
medline:
9
7
2024
pubmed:
9
7
2024
entrez:
9
7
2024
Statut:
epublish
Résumé
Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood. 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. 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. Our findings highlight the importance of causal genes for VV and provide new directions for treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood.
METHODS
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
RESULTS
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
CONCLUSIONS
Our findings highlight the importance of causal genes for VV and provide new directions for treatment.
Identifiants
pubmed: 38980841
doi: 10.1371/journal.pgen.1011339
pii: PGENETICS-D-23-01104
doi:
Substances chimiques
PIEZO1 protein, human
0
ECE1 protein, human
EC 3.4.24.71
Endothelin-Converting Enzymes
EC 3.4.24.71
Ion Channels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011339Informations de copyright
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.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.