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

Author

Listed:
  • Waheed-Ul-Rahman Ahmed

    (University of Oxford, Botnar Research Centre, Windmill Road)

  • Sam Kleeman

    (Cold Spring Harbor Laboratory)

  • Michael Ng

    (University of Oxford, Botnar Research Centre, Windmill Road)

  • Wei Wang

    (23andMe, Inc.)

  • Adam Auton

    (23andMe, Inc.)

  • Regent Lee

    (University of Oxford, John Radcliffe Hospital)

  • Ashok Handa

    (University of Oxford, John Radcliffe Hospital)

  • Krina T. Zondervan

    (University of Oxford, John Radcliffe Hospital
    University of Oxford, Old Road Campus, Roosevelt Drive)

  • Akira Wiberg

    (University of Oxford, Botnar Research Centre, Windmill Road
    Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital)

  • Dominic Furniss

    (University of Oxford, Botnar Research Centre, Windmill Road
    Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital)

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.

Suggested Citation

  • Waheed-Ul-Rahman Ahmed & Sam Kleeman & Michael Ng & Wei Wang & Adam Auton & Regent Lee & Ashok Handa & Krina T. Zondervan & Akira Wiberg & Dominic Furniss, 2022. "Genome-wide association analysis and replication in 810,625 individuals with varicose veins," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30765-y
    DOI: 10.1038/s41467-022-30765-y
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