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Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.

TitleGenetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.
Publication TypeJournal Article
Year of Publication2012
AuthorsTang W, Schwienbacher C, Lopez LM, Ben-Shlomo Y, Oudot-Mellakh T, Johnson AD, Samani NJ, Basu S, Gögele M, Davies G, Lowe GDO, Tregouet D-A, Tan A, Pankow JS, Tenesa A, Levy D, Volpato CB, Rumley A, Gow AJ, Minelli C, Yarnell JWG, Porteous DJ, Starr JM, Gallacher J, Boerwinkle E, Visscher PM, Pramstaller PP, Cushman M, Emilsson V, Plump AS, Matijevic N, Morange P-E, Deary IJ, Hicks AA
Secondary AuthorsFolsom AR
JournalAm J Hum Genet
Volume91
Issue1
Pagination152-62
Date Published2012 Jul 13
ISSN1537-6605
KeywordsCohort Studies, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Partial Thromboplastin Time, Polymorphism, Single Nucleotide, Prothrombin Time, Risk, Thromboembolism, Thrombosis
Abstract

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are clinical tests commonly used to screen for coagulation-factor deficiencies. One genome-wide association study (GWAS) has been reported previously for aPTT, but no GWAS has been reported for PT. We conducted a GWAS and meta-analysis to identify genetic loci for aPTT and PT. The GWAS for aPTT was conducted in 9,240 individuals of European ancestry from the Atherosclerosis Risk in Communities (ARIC) study, and the GWAS for PT was conducted in 2,583 participants from the Genetic Study of Three Population Microisolates in South Tyrol (MICROS) and the Lothian Birth Cohorts (LBC) of 1921 and 1936. Replication was assessed in 1,041 to 3,467 individuals. For aPTT, previously reported associations with KNG1, HRG, F11, F12, and ABO were confirmed. A second independent association in ABO was identified and replicated (rs8176704, p = 4.26 × 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 × 10(-9)) and AGBL1 (rs2469184, p = 3.61 × 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 × 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 × 10(-13)). Assessment of existing gene expression and coronary artery disease (CAD) databases identified associations of five of the GWAS loci with altered gene expression and two with CAD. In summary, eight genetic loci that account for ∼29% of the variance in aPTT and two loci that account for ∼14% of the variance in PT were detected and supported by functional data.

DOI10.1016/j.ajhg.2012.05.009
Alternate JournalAm J Hum Genet
PubMed ID22703881
PubMed Central IDPMC3397273
Grant ListPG/09/002/26056 / / British Heart Foundation / United Kingdom
R01 HL095603 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01-HL095603 / HL / NHLBI NIH HHS / United States
G0700704 / / Medical Research Council / United Kingdom
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom