TY - JOUR
T1 - Genetic associations for activated partial thromboplastin time and prothrombin time, their gene expression profiles, and risk of coronary artery disease
AU - Tang, Weihong
AU - Schwienbacher, Christine
AU - Lopez, Lorna M.
AU - Ben-Shlomo, Yoav
AU - Oudot-Mellakh, Tiphaine
AU - Johnson, Andrew D.
AU - Samani, Nilesh J.
AU - Basu, Saonli
AU - Goegele, Martin
AU - Davies, Gail
AU - Lowe, Gordon D. O.
AU - Tregouet, David-Alexandre
AU - Tan, Adrian
AU - Pankow, James S.
AU - Tenesa, Albert
AU - Levy, Daniel
AU - Volpato, Claudia B.
AU - Rumley, Ann
AU - Gow, Alan J.
AU - Minelli, Cosetta
AU - Yarnell, John W. G.
AU - Porteous, David J.
AU - Starr, John M.
AU - Gallacher, John
AU - Boerwinkle, Eric
AU - Visscher, Peter M.
AU - Pramstaller, Peter P.
AU - Cushman, Mary
AU - Emilsson, Valur
AU - Plump, Andrew S.
AU - Matijevic, Nena
AU - Morange, Pierre-Emmanuel
AU - Deary, Ian J.
AU - Hicks, Andrew A.
AU - Folsom, Aaron R.
PY - 2012/7/13
Y1 - 2012/7/13
N2 - 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 x 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 x 10(-9)) and AGBL1 (rs2469184, p = 3.61 x 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 x 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 x 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 similar to 29% of the variance in aPTT and two loci that account for similar to 14% of the variance in PT were detected and supported by functional data.
AB - 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 x 10(-24)). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 x 10(-9)) and AGBL1 (rs2469184, p = 3.61 x 10(-8)). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 x 10(-56)) and PROCR/EDEM2 (rs2295888, p = 5.25 x 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 similar to 29% of the variance in aPTT and two loci that account for similar to 14% of the variance in PT were detected and supported by functional data.
KW - HEMOSTASIS PHENOTYPES
KW - GENOME-WIDE ASSOCIATION
KW - HISTIDINE-RICH GLYCOPROTEIN
KW - PROTEIN-C
KW - VENOUS THROMBOEMBOLISM
KW - VON-WILLEBRAND-FACTOR
KW - CELLULAR CHARACTERIZATION
KW - ABO BLOOD-GROUP
KW - PLASMA-LEVELS
KW - DEEP-VEIN THROMBOSIS
U2 - 10.1016/j.ajhg.2012.05.009
DO - 10.1016/j.ajhg.2012.05.009
M3 - Article
C2 - 22703881
SN - 0002-9297
VL - 91
SP - 152
EP - 162
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -