Genetic Associations for Activated Partial Thromboplastin Time and Prothrombin Time, their Gene Expression Profiles, and Risk of Coronary Artery Disease

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

作者机构：Univ Minnesota Div Epidemiol & Community Hlth Minneapolis MN 55454 USA European Acad Bozen Bolzano EURAC Ctr Biomed I-39100 Bolzano Italy Univ Ferrara Dept Expt & Diagnost Med I-44121 Ferrara Italy Univ Edinburgh Ctr Cognit Ageing & Cognit Epidemiol Edinburgh EH8 9JZ Midlothian Scotland Univ Edinburgh Dept Psychol Edinburgh EH8 9JZ Midlothian Scotland Univ Bristol Sch Social & Community Med Bristol BS8 2PS Avon England Univ Paris 06 INSERM UMR S 937 Inst Cardiometab & Nutr ICAN F-75013 Paris France NHLBI Framingham Heart Study Framingham MA 01702 USA NHLBI Ctr Populat Studies Bethesda MD 20824 USA NHLBI Div Intramural Res Bethesda MD 20824 USA Univ Leicester Glenfield Hosp Dept Cardiovasc Sci Leicester LE3 9QP Leics England Leicester Cardiovasc Biomed Res Unit Glenfield Hosp Natl Inst Hlth Res Leicester LE3 9QP Leics England Univ Minnesota Div Biostat Minneapolis MN 55455 USA Univ Glasgow Inst Cardiovasc & Med Sci Glasgow G12 8TA Lanark Scotland Inst Genet & Mol Med Med Res Council MRC Human Genet Unit Edinburgh EH4 2XU Midlothian Scotland Univ Edinburgh Royal Dick Sch Vet Studies Roslin Inst Roslin EH25 9RG Midlothian Scotland Queens Univ Belfast Epidemiol Res Grp Belfast BT12 6BJ Antrim North Ireland Univ Edinburgh Med Genet Sect Edinburgh EH4 2XU Midlothian Scotland Univ Edinburgh Alzheimer Scotland Dementia Res Ctr Edinburgh EH8 9JZ Midlothian Scotland Cardiff Univ Sch Med Dept Primary Care & Publ Hlth Cardiff CF14 4XN S Glam Wales Univ Texas Hlth Sci Ctr Houston Ctr Human Genet Houston TX 77030 USA Univ Texas Hlth Sci Ctr Houston Human Genome Sequencing Ctr Houston TX 77030 USA Queensland Inst Med Res Brisbane Qld 4029 Australia Gen Cent Hosp Dept Neurol I-39100 Bolzano Italy Univ Lubeck Dept Neurol D-23538 Lubeck Germany Univ Vermont Dept Med Burlington VT 05405 USA Univ Vermont Dept Pathol Burlington VT 05405 USA Merck & Co Inc Mol Programming & Res Informat Rahway NJ 07065 USA Merck Res Lab Dept Cardiovasc Dis Rahway NJ 07065 USA Univ Texas Hlth Sci Ctr Houston Hemostasis Lab Houston TX 77030 USA Aix Marseille Univ INSERM UMR S 1062 F-13385 Marseille France 

出 版 物：《AMERICAN JOURNAL OF HUMAN GENETICS》 (美国人类遗传学杂志)

年 卷 期：2012年第91卷第1期

页      面：152-162页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：National Institutes of Health (NIH) [R01-HL095603] BBSRC [BB/F019394/1] Funding Source: UKRI MRC [G0700704] Funding Source: UKRI 

主　　题：PARTIAL thromboplastin time PROTHROMBIN time GENE expression CORONARY heart disease -- Risk factors BLOOD coagulation HUMAN genome DNA replication 

摘      要：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.