Genetics of varicose veins reveals polygenic architecture and genetic overlap with arterial and venous disease

Levin, Michael G.; Huffman, Jennifer E.; Verma, Anurag; Sullivan, Kyle A.; Rodriguez, Alexis A.; Kainer, David; Garvin, Michael R.; Lane, Matthew; Cashman, Mikaela; Miller, J. Izaak; Won, Hyejung; Li, Binglan; Luo, Yuan; Jarvik, Gail P.; Hakonarson, Hakon; Jasper, Elizabeth A.; Bick, Alexander G.; Tsao, Philip S.; Ritchie, Marylyn D.; Jacobson, Daniel A.; Madduri, Ravi K.; Damrauer, Scott M.

doi:10.1038/s44161-022-00196-5

Genetics of varicose veins reveals polygenic architecture and genetic overlap with arterial and venous disease

Journal Article · Mon Jan 09 00:00:00 EST 2023 · Nature Cardiovascular Research

DOI:https://doi.org/10.1038/s44161-022-00196-5· OSTI ID:1909145

^[1]; ^[2]; Verma, Anurag ^[3]; ^[4]; Rodriguez, Alexis A. ^[5]; Kainer, David ^[4]; ^[4]; ^[6]; Cashman, Mikaela ^[4]; Miller, J. Izaak ^[4]; ^[7]; ^[8]; ^[9]; ^[10]; Hakonarson, Hakon ^[11]; Jasper, Elizabeth A. ^[12]; ^[13]; Tsao, Philip S. ^[14]; ^[15]; ^[4] more »

Univ. of Pennsylvania, Philadelphia, PA (United States); Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA (United States)
VA Boston Healthcare System, Boston, MA (United States). Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC)
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA (United States); Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Argonne National Lab. (ANL), Lemont, IL (United States)
Univ. of Tennessee, Knoxville, TN (United States)
Univ. of North Carolina, Chapel Hill, NC (United States)
Stanford Univ., CA (United States)
Northwestern Univ., Chicago, IL (United States). Feinberg School of Medicine
Univ. of Washington Medical Center, Seattle, WA (United States)
The Children’s Hospital of Philadelphia, PA (United States)
Vanderbilt University Medical Center, Nashville, TN (United States)
Vanderbilt Univ., Nashville, TN (United States). School of Medicine
VA Palo Alto Health Care System, Palo Alto, CA (United States); Stanford Univ., CA (United States). School of Medicine
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine

Varicose veins represent a common cause of cardiovascular morbidity, with limited available medical therapies. Although varicose veins are heritable and epidemiologic studies have identified several candidate varicose vein risk factors, the molecular and genetic basis remains uncertain. Here we analyzed the contribution of common genetic variants to varicose veins using data from the Veterans Affairs Million Veteran Program and four other large biobanks. Among 49,765 individuals with varicose veins and 1,334,301 disease-free controls, we identified 139 risk loci. We identified genetic overlap between varicose veins, other vascular diseases and dozens of anthropometric factors. Using Mendelian randomization, we prioritized therapeutic targets via integration of proteomic and transcriptomic data. Finally, topological enrichment analyses confirmed the biologic roles of endothelial shear flow disruption, inflammation, vascular remodeling and angiogenesis. Further, these findings may facilitate future efforts to develop nonsurgical therapies for varicose veins.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: National Institutes of Health (NIH), National Heart, Lung and Blood Institute (NHLBI); US Department of Veterans Affairs (VA); USDOE

Contributing Organization:: VA Million Veteran Program

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1909145

Journal Information:: Nature Cardiovascular Research, Journal Name: Nature Cardiovascular Research Vol. 2; ISSN 2731-0590

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: English

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