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Updated: Jun 21, 2025

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Exome sequencing identifies novel genetic variants associated with varicose veins
Dan-Dan Zhang1, Xiao-Yu He2, Liu Yang2
1Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
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.
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