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

Weihong Tang, Christine Schwienbacher, Lorna M. Lopez, Yoav Ben-Shlomo, Tiphaine Oudot-Mellakh, Andrew D. Johnson, Nilesh J. Samani, Saonli Basu, Martin Gögele, Gail Davies, Gordon D O Lowe, David Alexandre Tregouet, Adrian Tan, James S. Pankow, Albert Tenesa, Daniel Levy, Claudia B. Volpato, Ann Rumley, Alan J. Gow, Cosetta MinelliJohn W G Yarnell, David J. Porteous, John M. Starr, John Gallacher, Eric Boerwinkle, Peter M. Visscher, Peter P. Pramstaller, Mary Cushman, Valur Emilsson, Andrew S. Plump, Nena Matijevic, Pierre Emmanuel Morange, Ian J. Deary, Andrew A. Hicks, Aaron R. Folsom

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)152-162
Number of pages11
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - Jul 13 2012

Bibliographical note

Funding Information:
We warmly thank all staff and participants. The individual studies were supported by the National Institutes of Health (NIH) or other funding sources. W.T. is partially supported by NIH grant R01-HL095603. We would like to thank the University of Minnesota Supercomputing Institute for use of the Blade and Calhoun supercomputers. Additional acknowledgments for each study and conflict-of-interest disclosures are listed in the Supplemental Data.


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