Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.
Authors | |
Abstract | Venous thromboembolism is a significant cause of mortality, 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. |
Year of Publication | 2019
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Journal | Nat Genet
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Volume | 51
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Issue | 11
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Pages | 1574-1579
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Date Published | 2019 Nov
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ISSN | 1546-1718
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DOI | 10.1038/s41588-019-0519-3
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PubMed ID | 31676865
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PubMed Central ID | PMC6858581
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Links | |
Grant list | I01 CX001025 / CX / CSRD VA / United States
HHSN268201600018C / HL / NHLBI NIH HHS / United States
I01-01BX03340 / U.S. Department of Veterans Affairs (Department of Veterans Affairs)
R01 HL116854 / HL / NHLBI NIH HHS / United States
RES 13-457 / RD / ORD VA / United States
R01 HL127564 / HL / NHLBI NIH HHS / United States
HL116854 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
I01-BX003362 / U.S. Department of Veterans Affairs (Department of Veterans Affairs)
R01 HL142711 / HL / NHLBI NIH HHS / United States
K08 HL140203 / HL / NHLBI NIH HHS / United States
IK2 CX001780 / CX / CSRD VA / United States
HHSN268201600003C / HL / NHLBI NIH HHS / United States
I01 BX003340 / BX / BLRD VA / United States
IK2-CX001780 / U.S. Department of Veterans Affairs (Department of Veterans Affairs)
HHSN268201600004C / HL / NHLBI NIH HHS / United States
I01-CX001025 / U.S. Department of Veterans Affairs (Department of Veterans Affairs)
HHSN268201600001C / HL / NHLBI NIH HHS / United States
I01 BX003362 / BX / BLRD VA / United States
K08HL140203 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
R01HL127564 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
R01HL142711 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
HHSN268201600002C / BC / NCI NIH HHS / United States
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