{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:29:09Z","timestamp":1788805749480,"version":"build-2803163510"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Fibrinogen is a multifunctional circulating glycoprotein involved in wound healing, thrombosis, platelet aggregation, and inflammation, and elevated levels predict vascular disease. Despite evidence of crucial biological function and moderate heritability, comprehensive analysis of the influence of genetic variation on fibrinogen is not available.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            To address this issue, we undertook a genome-wide association study evaluating the potential relationships between 337 343 single-nucleotide polymorphisms (SNPs) and plasma fibrinogen levels among 17 686 apparently healthy women participating in the Women\u2019s Genome Health Study. As C-reactive protein is also an inflammatory marker known to predict cardiovascular diseases, we compared the determinants of fibrinogen levels with those of C-reactive protein. Four novel loci were identified, in addition to the fibrinogen gene cluster, which were associated with fibrinogen levels at genome-wide levels of significance (range of probability values from 8.82\ufffd10\n            <jats:sup>\u221209<\/jats:sup>\n            to 8.04\ufffd10\n            <jats:sup>\u221239<\/jats:sup>\n            ). Two of the loci are related to common chronic inflammatory diseases: the first, at locus 5q31.1 (\n            <jats:italic>SLC22A5<\/jats:italic>\n            ,\n            <jats:italic>SLC22A4<\/jats:italic>\n            ,\n            <jats:italic>IRF1<\/jats:italic>\n            ), lies immediately adjacent to a locus linked to Crohn disease (\n            <jats:italic>P<\/jats:italic>\n            value for lead SNP, 1.24\ufffd10\n            <jats:sup>\u221212<\/jats:sup>\n            ) and the second, at locus 17q25.1 (\n            <jats:italic>CD300LF<\/jats:italic>\n            ,\n            <jats:italic>SLC9A3R1<\/jats:italic>\n            ,\n            <jats:italic>NAT9<\/jats:italic>\n            ), has been associated with psoriasis (\n            <jats:italic>P<\/jats:italic>\n            value for lead SNP, 7.72\ufffd10\n            <jats:sup>\u221211<\/jats:sup>\n            ). A third locus at 1q21.3 (\n            <jats:italic>IL6R<\/jats:italic>\n            ) lies within the interleukin 6 receptor gene, a critical component of the inflammatory cascade (\n            <jats:italic>P<\/jats:italic>\n            value for lead SNP, 1.80\ufffd10\n            <jats:sup>\u221211<\/jats:sup>\n            ). A novel locus at 2q34 (\n            <jats:italic>CPSI<\/jats:italic>\n            ) participates in the urea cycle (\n            <jats:italic>P<\/jats:italic>\n            =8.82\ufffd10\n            <jats:sup>\u221209<\/jats:sup>\n            ). The majority of implicated SNPs showed little evidence of dual association with C-reactive protein levels.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            A genome-wide survey of the human genome identifies novel loci related to common chronic inflammatory diseases as genetic determinants of fibrinogen levels, in addition to loci that relate to the inflammatory cascade, the urea cycle, and the fibrinogen gene cluster.\n          <\/jats:p>","DOI":"10.1161\/circgenetics.108.825273","type":"journal-article","created":{"date-parts":[[2009,2,13]],"date-time":"2009-02-13T03:01:04Z","timestamp":1234494064000},"page":"134-141","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Novel Loci, Including Those Related to Crohn Disease, Psoriasis, and Inflammation, Identified in a Genome-Wide Association Study of Fibrinogen in 17 686 Women"],"prefix":"10.1161","volume":"2","author":[{"given":"Jacqueline S.","family":"Danik","sequence":"first","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Pare\u0301","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel I.","family":"Chasman","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert Y.L.","family":"Zee","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Parker","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Miletich","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Ridker","sequence":"additional","affiliation":[{"name":"From the Center for Cardiovascular Disease Prevention (J.S.D., G.P., D.I.C., R.Y.L.Z., P.M.R.), Donald W. Reynolds Center for Cardiovascular Research (J.S.D., D.I.C., R.Y.L.Z., D.J.K., P.M.R.), and Translational Medicine Division, Brigham and Women\u2019s Hospital (D.J.K.), Boston, Mass; and Amgen, Inc (A.P., J.P.M.), Cambridge, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902113400607"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1987.03400090067035"},{"key":"e_1_3_2_3_2","first-page":"1799","volume":"294","year":"2005","unstructured":"Fibrinogen Studies Collaboration, 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-Pi\u00f1ango 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, Nyyss\u00f6nen K, Tuomainen TP, Hedblad B, Lind P, Loewel H, Koenig W, Meade TW, Cooper JA, De Stavola B, Knottenbelt C, Miller GJ, Cooper JA, 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, Despr\u00e9s 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, Lewington 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\u20131809.","journal-title":"JAMA"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.634089"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)92557-8"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960628)63:4<509::AID-AJMG1>3.0.CO;2-J"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)92205-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.19.12.3063"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000222011.13026.25"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.13.6.886"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.12.3489"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2007.099366"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.03.015"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614005"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/genetics\/132.2.583","volume":"132","year":"1992","unstructured":"Hudson RR, Slatkin M, Maddison WP. Estimation of levels of gene flow from DNA sequence data. Genetics. 1992; 132: 583\u2013589.","journal-title":"Genetics"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1847"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.108.825224"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092500"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-223"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05911"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1339"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1267"},{"key":"e_1_3_2_25_2","first-page":"54.","volume":"7","year":"2006","unstructured":"Santiago JL, Martinez A, de la Calle H, Fernandez-Arquero M, Figueredo MA, de la Concha EG, Urcelay E. Evidence for the association of the SLC22A4 and SLC22A5 genes with type 1 diabetes: a case control study. BMC Med Genet. 2006; 7: 54.","journal-title":"BMC Med Genet"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0851-y"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01288-6"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1349"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8178173"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1268"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1086\/513206"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s005920050147"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.11.014"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000112424.06921.52"}],"container-title":["Circulation: Cardiovascular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGENETICS.108.825273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:25:14Z","timestamp":1715563514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGENETICS.108.825273"}},"subtitle":["The Women\u2019s Genome Health Study"],"short-title":[],"issued":{"date-parts":[[2009,4]]},"references-count":34,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["10.1161\/CIRCGENETICS.108.825273"],"URL":"https:\/\/doi.org\/10.1161\/circgenetics.108.825273","relation":{},"ISSN":["1942-325X","1942-3268"],"issn-type":[{"value":"1942-325X","type":"print"},{"value":"1942-3268","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4]]}}}