@article{f0d3474672ab47259407868ae08e20ac,
title = "Genetic Predictors of Fibrin D-Dimer Levels in Healthy Adults",
abstract = "Background-Fibrin fragment D-dimer, one of several peptides produced when crosslinked fibrin is degraded by plasmin, is the most widely used clinical marker of activated blood coagulation. To identity genetic loci influencing D-dimer levels, we performed the first large-scale, genome-wide association search. Methods and Results-A genome-wide investigation of the genomic correlates of plasma D-dimer levels was conducted among 21 052 European-ancestry adults. Plasma levels of D-dimer were measured independently in each of 13 cohorts. Each study analyzed the association between approximate to 2.6 million genotyped and imputed variants across the 22 autosomal chromosomes and natural-log-transformed D-dimer levels using linear regression in additive genetic models adjusted for age and sex. Among all variants, 74 exceeded the genome-wide significance threshold and marked 3 regions. At 1p22, rs12029080 (P=6.4 x 10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4x10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9x10(-18)) was located between 2 fibrinogen genes: 10.4 kb downstream from FGG and 3.0 kb upstream from FGA. Variants were associated with a 0.099-, 0.096-, and 0.061-unit difference, respectively, in natural-log-transformed D-dimer and together accounted for 1.8% of the total variance. When adjusted for nonsynonymous substitutions in F5 and FGA loci known to be associated with D-dimer levels, there was no evidence of an additional association at either locus. Conclusions-Three genes were associated with fibrin D-dimer levels. Of these 3, the F3 association was the strongest, and has not been previously reported. (Circulation. 2011;123:1864-1872.)",
keywords = "epidemiology, fibrin fragment D, genome-wide association study, hemostasis, meta-analysis, thrombosis, genome-wide association, tissue-plasminogen activator, coronary, heart-disease, von-willebrand-factor, venous thromboembolism, thr312ala, polymorphism, cardiovascular health, myocardial-infarction, aging, research, risk",
author = "Smith, {Nicholas L} and Huffman, {Jennifer E} and Strachan, {David P} and Jie Huang and Abbas Dehghan and Stella Trompet and Lopez, {Lorna M} and So-Youn Shin and Jens Baumert and Veronique Vitart and Bis, {Joshua C} and Wild, {Sarah H} and Ann Rumley and Qiong Yang and Uitterlinden, {Andre G} and Stott, {David J} and Gail Davies and Carter, {Angela M} and Barbara Thorand and Ozren Pola{\v s}ek and Barbara McKnight and Harry Campbell and Rudnicka, {Alicja R} and Ming-Huei Chen and Buckley, {Brendan M} and Harris, {Sarah E} and Annette Peters and Drazen Pulanic and Thomas Lumley and {de Craen}, {Anton J M} and Liewald, {David C} and Christian Gieger and Susan Campbell and Ian Ford and Gow, {Alan J} and Michelle Luciano and Porteous, {David J} and Xiuqing Guo and Naveed Sattar and Albert Tenesa and Mary Cushman and Slagboom, {P Eline} and Visscher, {Peter M} and Spector, {Tim D} and Thomas Illig and Igor Rudan and Bovill, {Edwin G} and Wright, {Alan F} and McArdle, {Wendy L} and Geoffrey Tofler and Albert Hofman and Westendorp, {Rudi G J} and Starr, {John M} and Grant, {Peter J} and Mahir Karakas and Hastie, {Nicholas D} and Psaty, {Bruce M} and Wilson, {James F} and Lowe, {Gordon D O} and O'Donnell, {Christopher J} and Witteman, {Jacqueline C M} and Jukema, {J Wouter} and Deary, {Ian J} and Nicole Soranzo and Wolfgang Koenig and Caroline Hayward",
year = "2011",
month = apr,
doi = "10.1161/circulationaha.110.009480",
language = "English",
volume = "123",
pages = "1864--1872",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "17",
}