Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Circulation

Volumn 128, Issue 12, 2013, Pages 1310-1324

  Sabater Lleal, Maria ^c   Huang, Jie ^c   Chasman, Daniel ^c   Naitza, Silvia ^c   Dehghan, Abbas ^c   Johnson, Andrew D ^c   Teumer, Alexander ^c   Reiner, Alex P ^c   Folkersen, Lasse ^c   Basu, Saonli ^c   Rudnicka, Alicja R ^c   Trompet, Stella ^c   Mälarstig, Anders ^c   Baumert, Jens ^c   Bis, Joshua C ^c   Guo, Xiuqing ^c   Hottenga, Jouke J ^c   Shin, So Youn ^c   Lopez, Lorna M ^c   Lahti, Jari ^c   Tanaka, Toshiko ^c   Yanek, Lisa R ^c   Oudot Mellakh, Tiphaine ^c   Wilson, James F ^c   Navarro, Pau ^c   Huffman, Jennifer E ^c   Zemunik, Tatijana ^c   Redline, Susan ^c   Mehra, Reena ^c   Pulanic, Drazen ^c   Rudan, Igor ^c   Wright, Alan F ^c   Kolcic, Ivana ^c   Polasek, Ozren ^c   Wild, Sarah H ^c   Campbell, Harry ^c   Curb, J David ^c   Wallace, Robert ^c   Liu, Simin ^c   Eaton, Charles B ^c   Becker, Diane M ^c   Becker, Lewis C ^c   Bandinelli, Stefania ^c   Räikkönen, Katri ^c   Widen, Elisabeth ^c   Palotie, Aarno ^c   Fornage, Myriam ^c   Green, David ^c   Gross, Myron ^c   Davies, Gail ^c   Harris, Sarah E ^c   Liewald, David C ^c   Starr, John M ^c   Williams, Frances M K ^c   Grant, Peter J ^c   Spector, Timothy D ^c   Strawbridge, Rona J ^c   Silveira, Angela ^c   Sennblad, Bengt ^c   Rivadeneira, Fernando ^c   Uitterlinden, Andre G ^c   Franco, Oscar H ^c   Hofman, Albert ^c   Van Dongen, Jenny ^c   Willemsen, Gonneke ^c   Boomsma, Dorret I ^c   Yao, Jie ^c   Swords Jenny, Nancy ^c   Haritunians, Talin ^c   McKnight, Barbara ^c   Lumley, Thomas ^c   Taylor, Kent D ^c   Rotter, Jerome I ^c   Psaty, Bruce M ^c   Peters, Annette ^c   Gieger, Christian ^c   Illig, Thomas ^c   Grotevendt, Anne ^c   Homuth, Georg ^c   Völzke, Henry ^c   Kocher, Thomas ^c   Goel, Anuj ^c   Franzosi, Maria Grazia ^c   Seedorf, Udo ^c   Clarke, Robert ^c   Steri, Maristella ^c   Tarasov, Kirill V ^c   Sanna, Serena ^c   Schlessinger, David ^c   Stott, David J ^c   Sattar, Naveed ^c   Buckley, Brendan M ^c   Rumley, Ann ^c   Lowe, Gordon D ^c   McArdle, Wendy L ^c   Chen, Ming Huei ^c   Tofler, Geoffrey H ^c,d   Song, Jaejoon ^c   Boerwinkle, Eric ^c   Folsom, Aaron R ^c   Rose, Lynda M ^c   Franco Cereceda, Anders ^c   Teichert, Martina ^c   Ikram, M Arfan ^c   Mosley, Thomas H ^c   Bevan, Steve ^c   Dichgans, Martin ^c   Rothwell, Peter M ^c   Sudlow, Cathie L M ^c   Hopewell, Jemma C ^c   Chambers, John C ^c   Saleheen, Danish ^c   Kooner, Jaspal S ^c   Danesh, John ^c   Nelson, Christopher P ^c   Erdmann, Jeanette ^c   Reilly, Muredach P ^c   Kathiresan, Sekar ^c   Schunkert, Heribert ^c   Morange, Pierre Emmanuel ^c   Ferrucci, Luigi ^c   Eriksson, Johan G ^c   Jacobs, David ^c   Deary, Ian J ^c   Soranzo, Nicole ^c   Witteman, Jacqueline C M ^c   De Geus, Eco J C ^c   Tracy, Russell P ^c   Hayward, Caroline ^c   Koenig, Wolfgang ^c   Cucca, Francesco ^c   Jukema, J Wouter ^c   Eriksson, Per ^c   Seshadri, Sudha ^c   Markus, Hugh S ^c   Watkins, Hugh ^c   Samani, Nilesh J ^c   Wallaschofski, Henri ^c   Smith, Nicholas L ^c   Tregouet, David ^c   Ridker, Paul M ^c   Tang, Weihong ^c   Strachan, David P ^c   Hamsten, Anders ^a   O'Donnell, Christopher J ^b   more..

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b FRAMINGHAM HEART STUDY   (United States)

^c University of Sydney ^*

^d UNIVERSITY OF SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPOCYTOKINE; ALPHA ACTININ 1; FIBRINOGEN; INTERFERON REGULATORY FACTOR 1; PROTIRELIN;

ALPHA ACTININ 1 GENE; ARTICLE; CARDIOVASCULAR DISEASE; CD300LF GENE; CEREBROVASCULAR ACCIDENT; CHD9 GENE; CORONARY ARTERY DISEASE; CPS1 GENE; DIP2B GENE; ETHNIC DIFFERENCE; FARP2 GENE; FGB GENE; FIBRINOGEN BLOOD LEVEL; GENE; GENE EXPRESSION; GENE LOCUS; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; HGFAC GENE; HISPANIC; HUMAN; IL1F10 GENE; IL1R1 GENE; IL6R GENE; INFLAMMATION; INTERFERON REGULATORY FACTOR 1 GENE; JMJD1C GENE; LEPR GENE; LIVER; LRPAP1 GENE; MS4A6A GENE; MSL2 GENE; NLRP3 GENE; OUTCOME ASSESSMENT; PLEC1 GENE; PRIORITY JOURNAL; PRPS1L1 GENE; PSMG1 GENE; SHANK3 GENE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SPPL2A GENE; TOMM7 GENE; VENOUS THROMBOEMBOLISM;

EID: 84884250513     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.113.002251     Document Type: Article

References (39)

1. Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, Kostis JB, Wilson AC, Folsom AR, Wu K, Benderly M, Goldbourt U, Willeit J, Kiechl S, Yarnell JW, Sweetnam PM, Elwood PC, Cushman M, Psaty BM, Tracy RP, Tybjaerg-Hansen A, Haverkate F, de Maat MP, Fowkes FG, Lee AJ, Smith FB, Salomaa V, Harald K, Rasi R, Vahtera E, Jousilahti P, Pekkanen J, D'Agostino R, Kannel WB, Wilson PW, Tofler G, Arocha-Pinango CL, Rodriguez-Larralde A, Nagy E, Mijares M, Espinosa R, Rodriquez-Roa E, Ryder E, Diez-Ewald MP, Campos G, Fernandez V, Torres E, Marchioli R, Valagussa F, Rosengren A, Wilhelmsen L, Lappas G, Eriksson H, Cremer P, Nagel D, Curb JD, Rodriguez B, Yano K, Salonen JT, Nyyssonen K, Tuomainen TP, Hedblad B, Lind P, Loewel H, Koenig W, Meade TW, Cooper JA, De Stavola B, Knottenbelt C, Miller GJ, Bauer KA, Rosenberg RD, Sato S, Kitamura A, Naito Y, Palosuo T, Ducimetiere P, Amouyel P, Arveiler D, Evans AE, Ferrieres J, Juhan-Vague I, Bingham A, Schulte H, Assmann G, Cantin B, Lamarche B, Despres JP, Dagenais GR, Tunstall-Pedoe H, Woodward M, Ben-Shlomo Y, Davey Smith G, Palmieri V, Yeh JL, Rudnicka A, Ridker P, Rodeghiero F, Tosetto A, Shepherd J, Ford I, Robertson M, Brunner E, Shipley M, Feskens EJ, Kromhout D, Dickinson A, Ireland B, Juzwishin K, Kaptoge S, Memon A, Sarwar N, Walker M, Wheeler J, White I, Wood A. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294:1799-1809.
2. Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a metaanalysis and review of the literature. Ann Intern Med. 1993;118:956-963.
3. Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984;311:501-505.
4. Koster T, Rosendaal FR, Reitsma PH, van der Velden PA, Briët E, Vandenbroucke JP. Factor VII and fibrinogen levels as risk factors for venous thrombosis: a case-control study of plasma levels and DNA polymorphisms: the Leiden Thrombophilia Study (LETS). Thromb Haemost. 1994;71:719-722.
5. Uitte de Willige S, de Visser MC, Houwing-Duistermaat JJ, Rosendaal FR, Vos HL, Bertina RM. Genetic variation in the fibrinogen gamma gene increases the risk for deep venous thrombosis by reducing plasma fibrinogen gamma' levels. Blood. 2005;106:4176-4183.
6. de Lange M, Snieder H, Ariëns RA, Spector TD, Grant PJ. The genetics of haemostasis: a twin study. Lancet. 2001;357:101-105.
7. Souto JC, Almasy L, Borrell M, Garí M, Martínez E, Mateo J, Stone WH, Blangero J, Fontcuberta J. Genetic determinants of hemostasis phenotypes in Spanish families. Circulation. 2000;101:1546-1551.
8. Dehghan A, Yang Q, Peters A, Basu S, Bis JC, Rudnicka AR, Kavousi M, Chen MH, Baumert J, Lowe GD, McKnight B, Tang W, de Maat M, Larson MG, Eyhermendy S, McArdle WL, Lumley T, Pankow JS, Hofman A, Massaro JM, Rivadeneira F, Kolz M, Taylor KD, van Duijn CM, Kathiresan S, Illig T, Aulchenko YS, Volcik KA, Johnson AD, Uitterlinden AG, Tofler GH, Gieger C, Psaty BM, Couper DJ, Boerwinkle E, Koenig W, O'Donnell CJ, Witteman JC, Strachan DP, Smith NL, Folsom AR; Wellcome Trust Case Control Consortium. Association of novel genetic loci with circulating fibrinogen levels: a genome-wide association study in 6 population-based cohorts. Circ Cardiovasc Genet. 2009;2:125-133.
9. Danik JS, Paré G, Chasman DI, Zee RY, Kwiatkowski DJ, Parker A, Miletich JP, Ridker PM. Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study. Circ Cardiovasc Genet. 2009;2:134-141.
10. Yang J, Manolio TA, Pasquale LR, Boerwinkle E, Caporaso N, Cunningham JM, de Andrade M, Feenstra B, Feingold E, Hayes MG, Hill WG, Landi MT, Alonso A, Lettre G, Lin P, Ling H, Lowe W, Mathias RA, Melbye M, Pugh E, Cornelis MC, Weir BS, Goddard ME, Visscher PM. Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet. 2011;43:519-525.
11. Preuss M, König IR, Thompson JR, Erdmann J, Absher D, Assimes TL, Blankenberg S, Boerwinkle E, Chen L, Cupples LA, Hall AS, Halperin E, Hengstenberg C, Holm H, Laaksonen R, Li M, März W, McPherson R, Musunuru K, Nelson CP, Burnett MS, Epstein SE, O'Donnell CJ, Quertermous T, Rader DJ, Roberts R, Schillert A, Stefansson K, Stewart AF, Thorleifsson G, Voight BF, Wells GA, Ziegler A, Kathiresan S, Reilly MP, Samani NJ, Schunkert H; CARDIoGRAM Consortium. Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study: a genome-wide association meta-analysis involving more than 22 000 cases and 60 000 controls. Circ Cardiovasc Genet. 2010;3:475-483.
12. Bellenguez C, Bevan S, Gschwendtner A, Spencer CC, Burgess AI, Pirinen M, Jackson CA, Traylor M, Strange A, Su Z, Band G, Syme PD, Malik R, Pera J, Norrving B, Lemmens R, Freeman C, Schanz R, James T, Poole D, Murphy L, Segal H, Cortellini L, Cheng YC, Woo D, Nalls MA, Muller-Myhsok B, Meisinger C, Seedorf U, Ross-Adams H, Boonen S, Wloch-Kopec D, Valant V, Slark J, Furie K, Delavaran H, Langford C, Deloukas P, Edkins S, Hunt S, Gray E, Dronov S, Peltonen L, Gretarsdottir S, Thorleifsson G, Thorsteinsdottir U, Stefansson K, Boncoraglio GB, Parati EA, Attia J, Holliday E, Levi C, Franzosi MG, Goel A, Helgadottir A, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Duncanson A, Jankowski J, Mathew CG, Palmer CN, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Worrall BB, Kittner SJ, Mitchell BD, Kissela B, Meschia JF, Thijs V, Lindgren A, Macleod MJ, Slowik A, Walters M, Rosand J, Sharma P, Farrall M, Sudlow CL, Rothwell PM, Dichgans M, Donnelly P, Markus HS. Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat Genet. 2012;44:328-333.
13. Germain M, Saut N, Greliche N, Dina C, Lambert JC, Perret C, Cohen W, Oudot-Mellakh T, Antoni G, Alessi MC, Zelenika D, Cambien F, Tiret L, Bertrand M, Dupuy AM, Letenneur L, Lathrop M, Emmerich J, Amouyel P, Trégouët DA, Morange PE. Genetics of venous thrombosis: insights from a new genome wide association study. PLoS One. 2011;6:e25581.
14. Trégouët DA, Heath S, Saut N, Biron-Andreani C, Schved JF, Pernod G, Galan P, Drouet L, Zelenika D, Juhan-Vague I, Alessi MC, Tiret L, Lathrop M, Emmerich J, Morange PE. Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach. Blood. 2009;113:5298-5303.
15. Ikram MA, Seshadri S, Bis JC, Fornage M, DeStefano AL, Aulchenko YS, Debette S, Lumley T, Folsom AR, van den Herik EG, Bos MJ, Beiser A, Cushman M, Launer LJ, Shahar E, Struchalin M, Du Y, Glazer NL, Rosamond WD, Rivadeneira F, Kelly-Hayes M, Lopez OL, Coresh J, Hofman A, DeCarli C, Heckbert SR, Koudstaal PJ, Yang Q, Smith NL, Kase CS, Rice K, Haritunians T, Roks G, de Kort PL, Taylor KD, de Lau LM, Oostra BA, Uitterlinden AG, Rotter JI, Boerwinkle E, Psaty BM, Mosley TH, van Duijn CM, Breteler MM, Longstreth WT Jr, Wolf PA. Genomewide association studies of stroke. N Engl J Med. 2009;360:1718-1728.
16. Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, Preuss M, Stewart AF, Barbalic M, Gieger C, Absher D, Aherrahrou Z, Allayee H, Altshuler D, Anand SS, Andersen K, Anderson JL, Ardissino D, Ball SG, Balmforth AJ, Barnes TA, Becker DM, Becker LC, Berger K, Bis JC, Boekholdt SM, Boerwinkle E, Braund PS, Brown MJ, Burnett MS, Buysschaert I, Carlquist JF, Chen L, Cichon S, Codd V, Davies RW, Dedoussis G, Dehghan A, Demissie S, Devaney JM, Diemert P, Do R, Doering A, Eifert S, Mokhtari NE, Ellis SG, Elosua R, Engert JC, Epstein SE, de Faire U, Fischer M, Folsom AR, Freyer J, Gigante B, Girelli D, Gretarsdottir S, Gudnason V, Gulcher JR, Halperin E, Hammond N, Hazen SL, Hofman A, Horne BD, Illig T, Iribarren C, Jones GT, Jukema JW, Kaiser MA, Kaplan LM, Kastelein JJ, Khaw KT, Knowles JW, Kolovou G, Kong A, Laaksonen R, Lambrechts D, Leander K, Lettre G, Li M, Lieb W, Loley C, Lotery AJ, Mannucci PM, Maouche S, Martinelli N, McKeown PP, Meisinger C, Meitinger T, Melander O, Merlini PA, Mooser V, Morgan T, Mühleisen TW, Muhlestein JB, Münzel T, Musunuru K, Nahrstaedt J, Nelson CP, Nöthen MM, Olivieri O, Patel RS, Patterson CC, Peters A, Peyvandi F, Qu L, Quyyumi AA, Rader DJ, Rallidis LS, Rice C, Rosendaal FR, Rubin D, Salomaa V, Sampietro ML, Sandhu MS, Schadt E, Schäfer A, Schillert A, Schreiber S, Schrezenmeir J, Schwartz SM, Siscovick DS, Sivananthan M, Sivapalaratnam S, Smith A, Smith TB, Snoep JD, Soranzo N, Spertus JA, Stark K, Stirrups K, Stoll M, Tang WH, Tennstedt S, Thorgeirsson G, Thorleifsson G, Tomaszewski M, Uitterlinden AG, van Rij AM, Voight BF, Wareham NJ, Wells GA, Wichmann HE, Wild PS, Willenborg C, Witteman JC, Wright BJ, Ye S, Zeller T, Ziegler A, Cambien F, Goodall AH, Cupples LA, Quertermous T, März W, Hengstenberg C, Blankenberg S, Ouwehand WH, Hall AS, Deloukas P, Thompson JR, Stefansson K, Roberts R, Thorsteinsdottir U, O'Donnell CJ, McPherson R, Erdmann J, Samani NJ; Cardiogenics; CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333-338.
17. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, Seidel D. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Göttingen Risk Incidence and Prevalence Study (GRIPS). Eur J Clin Invest. 1994;24:444-453.
18. Clauss A. Rapid physiological coagulation method in determination of fibrinogen [in German]. Acta Haematol. 1957;17:237-246.
19. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol. 2010;34:816-834.
20. Marchini J, Howie B, Myers S, McVean G, Donnelly P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet. 2007;39:906-913.
21. Servin B, Stephens M. Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 2007;3:e114.
22. Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190-2191.
23. Raychaudhuri S, Plenge RM, Rossin EJ, Ng AC, Purcell SM, Sklar P, Scolnick EM, Xavier RJ, Altshuler D, Daly MJ; International Schizophrenia Consortium. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 2009;5:e1000534.
24. Segrè AV, Groop L, Mootha VK, Daly MJ, Altshuler D; DIAGRAM Consortium; MAGIC Investigators. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet. 2010;6:.
25. Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, Guiducci C, Catanese JJ, Xie G, Stahl EA, Chen R, Alfredsson L, Amos CI, Ardlie KG, Barton A, Bowes J, Burtt NP, Chang M, Coblyn J, Costenbader KH, Criswell LA, Crusius JB, Cui J, De Jager PL, Ding B, Emery P, Flynn E, Harrison P, Hocking LJ, Huizinga TW, Kastner DL, Ke X, Kurreeman FA, Lee AT, Liu X, Li Y, Martin P, Morgan AW, Padyukov L, Reid DM, Seielstad M, Seldin MF, Shadick NA, Steer S, Tak PP, Thomson W, van der Helm-van Mil AH, van der Horst-Bruinsma IE, Weinblatt ME, Wilson AG, Wolbink GJ, Wordsworth P, Altshuler D, Karlson EW, Toes RE, de Vries N, Begovich AB, Siminovitch KA, Worthington J, Klareskog L, Gregersen PK, Daly MJ, Plenge RM; BIRAC Consortium; YEAR Consortium. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet. 2009;41:1313-1318.
26. Folkersen L, van't Hooft F, Chernogubova E, Agardh HE, Hansson GK, Hedin U, Liska J, Syvänen AC, Paulsson-Berne G, Paulssson-Berne G, Franco-Cereceda A, Hamsten A, Gabrielsen A, Eriksson P; BiKE and ASAP Study Groups. Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease. Circ Cardiovasc Genet. 2010;3:365-373.
27. Greenawalt DM, Dobrin R, Chudin E, Hatoum IJ, Suver C, Beaulaurier J, Zhang B, Castro V, Zhu J, Sieberts SK, Wang S, Molony C, Heymsfield SB, Kemp DM, Reitman ML, Lum PY, Schadt EE, Kaplan LM. A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort. Genome Res. 2011;21:1008-1016.
28. Innocenti F, Cooper GM, Stanaway IB, Gamazon ER, Smith JD, Mirkov S, Ramirez J, Liu W, Lin YS, Moloney C, Aldred SF, Trinklein ND, Schuetz E, Nickerson DA, Thummel KE, Rieder MJ, Rettie AE, Ratain MJ, Cox NJ, Brown CD. Identification, replication, and functional finemapping of expression quantitative trait loci in primary human liver tissue. PLoS Genet. 2011;7:e1002078.
29. Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, Zhu J, Millstein J, Sieberts S, Lamb J, Guhathakurta D, Derry J, Storey JD, Avila-Campillo I, Kruger MJ, Johnson JM, Rohl CA, van Nas A, Mehrabian M, Drake TA, Lusis AJ, Smith RC, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich R. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6:e107.
30. Schröder A, Klein K, Winter S, Schwab M, Bonin M, Zell A, Zanger UM. Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver. Pharmacogenomics J. 2013;13:12-20.
31. Peden J, Hopewell JC, Saleheen D. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet. 2011;43:339-344.
32. Dehghan A, Dupuis J, Barbalic M, Bis JC, Eiriksdottir G, Lu C, Pellikka N, Wallaschofski H, Kettunen J, Henneman P, Baumert J, Strachan DP, Fuchsberger C, Vitart V, Wilson JF, Paré G, Naitza S, Rudock ME, Surakka I, de Geus EJ, Alizadeh BZ, Guralnik J, Shuldiner A, Tanaka T, Zee RY, Schnabel RB, Nambi V, Kavousi M, Ripatti S, Nauck M, Smith NL, Smith AV, Sundvall J, Scheet P, Liu Y, Ruokonen A, Rose LM, Larson MG, Hoogeveen RC, Freimer NB, Teumer A, Tracy RP, Launer LJ, Buring JE, Yamamoto JF, Folsom AR, Sijbrands EJ, Pankow J, Elliott P, Keaney JF, Sun W, Sarin AP, Fontes JD, Badola S, Astor BC, Hofman A, Pouta A, Werdan K, Greiser KH, Kuss O, Meyer zu Schwabedissen HE, Thiery J, Jamshidi Y, Nolte IM, Soranzo N, Spector TD, Völzke H, Parker AN, Aspelund T, Bates D, Young L, Tsui K, Siscovick DS, Guo X, Rotter JI, Uda M, Schlessinger D, Rudan I, Hicks AA, Penninx BW, Thorand B, Gieger C, Coresh J, Willemsen G, Harris TB, Uitterlinden AG, Järvelin MR, Rice K, Radke D, Salomaa V, Willems van Dijk K, Boerwinkle E, Vasan RS, Ferrucci L, Gibson QD, Bandinelli S, Snieder H, Boomsma DI, Xiao X, Campbell H, Hayward C, Pramstaller PP, van Duijn CM, Peltonen L, Psaty BM, Gudnason V, Ridker PM, Homuth G, Koenig W, Ballantyne CM, Witteman JC, Benjamin EJ, Perola M, Chasman DI. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation. 2011;123:731-738.
33. Associations of plasma fibrinogen levels with established cardiovascular disease risk factors, inflammatory markers, and other characteristics: individual participant meta-analysis of 154,211 adults in 31 prospective studies: the Fibrinogen Studies Collaboration. Am J Epidemiol. 2007;166:867-879.
34. Palmieri V, Celentano A, Roman MJ, de Simone G, Best L, Lewis MR, Robbins DC, Fabsitz RR, Howard BV, Devereux RB; Strong Heart Study. Relation of fibrinogen to cardiovascular events is independent of preclinical cardiovascular disease: the Strong Heart Study. Am Heart J. 2003;145:467-474.
35. Keavney B, Danesh J, Parish S, Palmer A, Clark S, Youngman L, Delépine M, Lathrop M, Peto R, Collins R. Fibrinogen and coronary heart disease: test of causality by "mendelian randomization." Int J Epidemiol. 2006;35:935-943.
36. Smith GD, Harbord R, Milton J, Ebrahim S, Sterne JA. Does elevated plasma fibrinogen increase the risk of coronary heart disease? Evidence from a meta-analysis of genetic association studies. Arterioscler Thromb Vasc Biol. 2005;25:2228-2233.
37. Kannel WB, Wolf PA, Castelli WP, D'Agostino RB. Fibrinogen and risk of cardiovascular disease: the Framingham Study. JAMA. 1987;258:1183-1186.
38. Lee AJ, Lowe GD, Woodward M, Tunstall-Pedoe H. Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. Br Heart J. 1993;69:338-342.
39. Qizilbash N, Jones L, Warlow C, Mann J. Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. BMJ. 1991;303:605-609.