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

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.

SUBMITTER: Tang W

PROVIDER: S-EPMC3397273 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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

Tang Weihong W Schwienbacher Christine C Lopez Lorna M LM Ben-Shlomo Yoav Y Oudot-Mellakh Tiphaine T Johnson Andrew D AD Samani Nilesh J NJ Basu Saonli S Gögele Martin M Davies Gail G Lowe Gordon D O GD Tregouet David-Alexandre DA Tan Adrian A Pankow James S JS Tenesa Albert A Levy Daniel D Volpato Claudia B CB Rumley Ann A Gow Alan J AJ Minelli Cosetta C Yarnell John W G JW Porteous David J DJ Starr John M JM Gallacher John J Boerwinkle Eric E Visscher Peter M PM Pramstaller Peter P PP Cushman Mary M Emilsson Valur V Plump Andrew S AS Matijevic Nena N Morange Pierre-Emmanuel PE Deary Ian J IJ Hicks Andrew A AA Folsom Aaron R AR

American journal of human genetics 20120614 1

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 P ...[more]

PMID: 22703881

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Project description:BackgroundA substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful.Methods and findingsWe evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing.ConclusionsThis study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

Dataset Information

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

Publications

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

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