Genome-wide association analysis and replication in 810,625 individuals with varicose veins.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 06 2022
02 06 2022
Historique:
received:
12
06
2021
accepted:
17
05
2022
entrez:
2
6
2022
pubmed:
3
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35654884
doi: 10.1038/s41467-022-30765-y
pii: 10.1038/s41467-022-30765-y
pmc: PMC9163161
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3065Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N001524/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Investigateurs
Michelle Agee
(M)
Stella Aslibekyan
(S)
Robert K Bell
(RK)
Katarzyna Bryc
(K)
Sarah K Clark
(SK)
Sarah L Elson
(SL)
Kipper Fletez-Brant
(K)
Pierre Fontanillas
(P)
Nicholas A Furlotte
(NA)
Pooja M Gandhi
(PM)
Karl Heilbron
(K)
Barry Hicks
(B)
David A Hinds
(DA)
Karen E Huber
(KE)
Ethan M Jewett
(EM)
Yunxuan Jiang
(Y)
Aaron Kleinman
(A)
Keng-Han Lin
(KH)
Nadia K Litterman
(NK)
Marie K Luff
(MK)
Jennifer C McCreight
(JC)
Matthew H McIntyre
(MH)
Kimberly F McManus
(KF)
Joanna L Mountain
(JL)
Sahar V Mozaffari
(SV)
Priyanka Nandakumar
(P)
Elizabeth S Noblin
(ES)
Carrie A M Northover
(CAM)
Jared O'Connell
(J)
Aaron A Petrakovitz
(AA)
Steven J Pitts
(SJ)
G David Poznik
(GD)
J Fah Sathirapongsasuti
(JF)
Anjali J Shastri
(AJ)
Janie F Shelton
(JF)
Suyash Shringarpure
(S)
Chao Tian
(C)
Joyce Y Tung
(JY)
Robert J Tunney
(RJ)
Vladimir Vacic
(V)
Xin Wang
(X)
Amir S Zare
(AS)
Informations de copyright
© 2022. The Author(s).
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