Genome-wide association analysis and replication in 810,625 individuals with varicose veins

Ahmed, Waheed-Ul-Rahman, Kleeman, Sam, Ng, Michael, Wang, Wei, Auton, Adam, 23andMe Research Team, Lee, Regent, Handa, Ashok, Zondervan, Krina T, Wiberg, Akira, Furniss, Dominic (June 2022) Genome-wide association analysis and replication in 810,625 individuals with varicose veins. Nature Communications, 13 (1). p. 3065. ISSN 2041-1723

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Abstract

Varicose veins affect one-third of Western society, with a significant subset of patients developing venous ulceration, costing $14.9 billion annually in the USA. Current management consists of either compression stockings, or surgical ablation for more advanced disease. Most varicose veins patients report a positive family history, and heritability is ~17%. We describe the largest two-stage genome-wide association study of varicose veins in 401,656 individuals from UK Biobank, and replication in 408,969 individuals from 23andMe (total 135,514 cases and 675,111 controls). Forty-nine signals at 46 susceptibility loci were discovered. We map 237 genes to these loci, several of which are biologically plausible and tractable to therapeutic targeting. Pathway analysis identified enrichment in extracellular matrix biology, inflammation, (lymph)angiogenesis, vascular smooth muscle cell migration, and apoptosis. Using a polygenic risk score (PRS) derived in an independent cohort, we demonstrate its predictive utility and correlation with varicose veins surgery.

Item Type:	Paper
Subjects:	Investigative techniques and equipment Investigative techniques and equipment > assays Investigative techniques and equipment > assays > genome wide association studies
CSHL Authors:	Kleeman, Sam
Communities:	CSHL labs > Janowitz lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 June 2022
Date Deposited:	23 Jun 2022 23:00
Last Modified:	29 Feb 2024 17:10
PMCID:	PMC9163161
URI:	https://repository.cshl.edu/id/eprint/40660

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