Genome-wide association analysis and replication in 810,625 individuals with varicose veins
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Published:2022-06-02
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Ahmed Waheed-Ul-RahmanORCID, Kleeman SamORCID, Ng MichaelORCID, Wang WeiORCID, Auton Adam, Agee Michelle, Aslibekyan Stella, Bell Robert K., Bryc Katarzyna, Clark Sarah K., Elson Sarah L., Fletez-Brant Kipper, Fontanillas Pierre, Furlotte Nicholas A., Gandhi Pooja M., Heilbron Karl, Hicks Barry, Hinds David A., Huber Karen E., Jewett Ethan M., Jiang Yunxuan, Kleinman Aaron, Lin Keng-Han, Litterman Nadia K., Luff Marie K., McCreight Jennifer C., McIntyre Matthew H., McManus Kimberly F., Mountain Joanna L., Mozaffari Sahar V., Nandakumar Priyanka, Noblin Elizabeth S., Northover Carrie A. M., O’Connell Jared, Petrakovitz Aaron A., Pitts Steven J., Poznik G. David, Sathirapongsasuti J. Fah, Shastri Anjali J., Shelton Janie F., Shringarpure Suyash, Tian Chao, Tung Joyce Y., Tunney Robert J., Vacic Vladimir, Wang Xin, Zare Amir S., Lee RegentORCID, Handa Ashok, Zondervan Krina T., Wiberg AkiraORCID, Furniss DominicORCID,
Abstract
AbstractVaricose 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.
Funder
Oxford NIHR Biomedical Research Centre UKRI Future Leaders Fellowship RCUK | MRC | Medical Research Foundation NIHR Clinical Lectureship
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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