04787nas a2201105 4500008004100000022001400041245006700055210006500122260001600187300001200203490000800215520177000223653001001993653000902003653002202012653004002034653001302074653001102087653004302098653001502141653002002156653003402176653001102210653000902221653001602230653002102246653001902267100002302286700002502309700002302334700001502357700001902372700002002391700002002411700001802431700001802449700002202467700001902489700001902508700001602527700001602543700002802559700002002587700001702607700002202624700002102646700001902667700002202686700002002708700002402728700002002752700002402772700002102796700002002817700002002837700001902857700002502876700002202901700002202923700002002945700001402965700001702979700002202996700002303018700001703041700001903058700001903077700001803096700002003114700002303134700002003157700001803177700001603195700002103211700002003232700002203252700002103274700001903295700002603314700001903340700002003359700001903379700002403398700002003422700002103442700002203463700003003485700003003515700001903545700001803564700002003582700002103602700002203623856003603645 2011 eng d a1524-453900aGenetic predictors of fibrin D-dimer levels in healthy adults.0 aGenetic predictors of fibrin Ddimer levels in healthy adults c2011 May 03 a1864-720 v1233 a
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 ≈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=6.4×10(-52)) was 46.0 kb upstream from F3, coagulation factor III (tissue factor). At 1q24, rs6687813 (P=2.4×10(-14)) was 79.7 kb downstream of F5, coagulation factor V. At 4q32, rs13109457 (P=2.9×10(-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.
10aAdult10aAged10aBlood Coagulation10aEuropean Continental Ancestry Group10aFactor V10aFemale10aFibrin Fibrinogen Degradation Products10aFibrinogen10aGenetic Testing10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aReference Values10aThromboplastin1 aSmith, Nicholas, L1 aHuffman, Jennifer, E1 aStrachan, David, P1 aHuang, Jie1 aDehghan, Abbas1 aTrompet, Stella1 aLopez, Lorna, M1 aShin, So-Youn1 aBaumert, Jens1 aVitart, Veronique1 aBis, Joshua, C1 aWild, Sarah, H1 aRumley, Ann1 aYang, Qiong1 aUitterlinden, André, G1 aStott, David, J1 aDavies, Gail1 aCarter, Angela, M1 aThorand, Barbara1 aPolasek, Ozren1 aMcKnight, Barbara1 aCampbell, Harry1 aRudnicka, Alicja, R1 aChen, Ming-Huei1 aBuckley, Brendan, M1 aHarris, Sarah, E1 aPeters, Annette1 aPulanic, Drazen1 aLumley, Thomas1 ade Craen, Anton, J M1 aLiewald, David, C1 aGieger, Christian1 aCampbell, Susan1 aFord, Ian1 aGow, Alan, J1 aLuciano, Michelle1 aPorteous, David, J1 aGuo, Xiuqing1 aSattar, Naveed1 aTenesa, Albert1 aCushman, Mary1 aSlagboom, Eline1 aVisscher, Peter, M1 aSpector, Tim, D1 aIllig, Thomas1 aRudan, Igor1 aBovill, Edwin, G1 aWright, Alan, F1 aMcArdle, Wendy, L1 aTofler, Geoffrey1 aHofman, Albert1 aWestendorp, Rudi, G J1 aStarr, John, M1 aGrant, Peter, J1 aKarakas, Mahir1 aHastie, Nicholas, D1 aPsaty, Bruce, M1 aWilson, James, F1 aLowe, Gordon, D O1 aO'Donnell, Christopher, J1 aWitteman, Jacqueline, C M1 aJukema, Wouter1 aDeary, Ian, J1 aSoranzo, Nicole1 aKoenig, Wolfgang1 aHayward, Caroline uhttps://chs-nhlbi.org/node/1284