WFRF:(de Maat MPM)
Sökning: WFRF:(de Maat MPM) > A genome-wide assoc...
A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology
-
- de Vries, PS (författare)
- Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands,Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Boston Univ, Dept Neurol, Boston, MA 02215 USA;Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA
-
- Sabater-Lleal, M (författare)
- Karolinska Institutet,Inst Invest Biomed St Pau, Unit Genom Complex Dis, Barcelona, Spain;Karolinska Inst, Dept Med, Cardiovasc Med Unit, Stockholm, Sweden;Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden
-
- Huffman, JE (författare)
- NHLBI, Populat Sci Branch, NIH, Framingham, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Vet Affairs VA Boston Healthcare Syst, Ctr Populat Genom, Jamaica Plain, MA USA
- visa fler...
- Seshadri, S (författare)
- Psaty, BM (författare)
- Rosendaal, FR (författare)
- Johnson, AD (författare)
- visa färre...
- (creator_code:org_t)
- American Society of Hematology, 2019
- 2019
- Engelska.
- Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 133:9, s. 967-977
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary analysis included all 9 studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using small-interfering RNA and then measuring F7 messenger RNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke (IS), and venous thromboembolism. We identified 2 novel (REEP3 and JAZF1-AS1) and 6 known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, whereas silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of IS. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of IS in the general population.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta mer i SwePub
- Av författaren/redakt...
- de Vries, PS
- Sabater-Lleal, M
- Huffman, JE
- Marten, J
- Song, Ci
- Pankratz, N
- visa fler...
- Bartz, TM
- de Haan, HG
- Delgado, GE
- Eicher, JD
- Martinez-Perez, ...
- Ward-Caviness, C ...
- Brody, JA
- Chen, MH
- de Maat, MPM
- Franberg, M
- Gill, D
- Kleber, ME
- Rivadeneira, F
- Soria, JM
- Tang, WH
- Tofler, GH
- Uitterlinden, AG
- Vlieg, AV
- Seshadri, S
- Boerwinkle, E
- Davies, NM
- Giese, AK
- Ikram, MK
- Kittner, SJ
- McKnight, B
- Psaty, BM
- Reiner, AP
- Sargurupremraj, ...
- Taylor, KD
- Fornage, M
- Hamsten, A
- Marz, W
- Rosendaal, FR
- Souto, JC
- Dehghan, A
- Johnson, AD
- Morrison, AC
- O'Donnell, CJ
- Smith, NL
- visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
- MEDICIN OCH HÄLS ...
- och Klinisk medicin
- och Kardiologi
- Artiklar i publikationen
- Blood
- Av lärosätet
- Karolinska Institutet
- Uppsala universitet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
