Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease.
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.
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, 55454, USA. tang0097@umn.edu
Weihong
W
Tang
Christine
C
Schwienbacher
Lorna M
LM
Lopez
Yoav
Y
Ben-Shlomo
Tiphaine
T
Oudot-Mellakh
Andrew D
AD
Johnson
Nilesh J
NJ
Samani
Saonli
S
Basu
Martin
M
Gögele
Gail
G
Davies
Gordon D O
GD
Lowe
David-Alexandre
DA
Tregouet
Adrian
A
Tan
James S
JS
Pankow
Albert
A
Tenesa
Daniel
D
Levy
Claudia B
CB
Volpato
Ann
A
Rumley
Alan J
AJ
Gow
Cosetta
C
Minelli
John W G
JW
Yarnell
David J
DJ
Porteous
John M
JM
Starr
John
J
Gallacher
Eric
E
Boerwinkle
Peter M
PM
Visscher
Peter P
PP
Pramstaller
Mary
M
Cushman
Valur
V
Emilsson
Andrew S
AS
Plump
Nena
N
Matijevic
Pierre-Emmanuel
PE
Morange
Ian J
IJ
Deary
Andrew A
AA
Hicks
Aaron R
AR
Folsom
D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D020641:Polymorphism, Single Nucleotide; D011517:Prothrombin Time; D012306:Risk; D013923:Thromboembolism / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics*