| Title: | Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease |
| Journal: | Nature Genetics |
| Published: | 1 Nov 2019 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31676865/ |
| DOI: | https://doi.org/10.1038/s41588-019-0519-3 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858581 |
| Citations: | 177 (73 in last 2 years) as of 8 Aug 2024 |
Publication 5011
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Abstract
Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.</p>
17 Keywords
- Aged
- Animals
- Case-Control Studies
- Female
- Genetic Loci
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- Middle Aged
- Plasminogen Activator Inhibitor 1
- Risk Factors
- United Kingdom
- Vascular Diseases
- Venous Thromboembolism
42 Authors
- Derek Klarin
- Emma Busenkell
- Renae Judy
- Julie Lynch
- Michael Levin
- Jeffery Haessler
- Krishna Aragam
- Mark Chaffin
- Mary Haas
- Sara Lindström
- Themistocles L. Assimes
- Jie Huang
- Kyung Min Lee
- Qing Shao
- Jennifer E. Huffman
- Christopher Kabrhel
- Yunfeng Huang
- Yan V. Sun
- Marijana Vujkovic
- Danish Saleheen
- Donald R. Miller
- Peter Reaven
- Scott DuVall
- William E. Boden
- Saiju Pyarajan
- Alex P. Reiner
- David-Alexandre Trégouët
- Peter Henke
- Charles Kooperberg
- J. Michael Gaziano
- John Concato
- Daniel J. Rader
- Kelly Cho
- Kyong-Mi Chang
- Peter W. F. Wilson
- Nicholas L. Smith
- Christopher J. O'Donnell
- Philip S. Tsao
- Sekar Kathiresan
- Andrea Obi
- Scott M. Damrauer
- Pradeep Natarajan
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