Title | A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | de Vries, PS, Chasman, DI, Sabater-Lleal, M, Chen, M-H, Huffman, JE, Steri, M, Tang, W, Teumer, A, Marioni, RE, Grossmann, V, Hottenga, JJ, Trompet, S, Müller-Nurasyid, M, Zhao, JH, Brody, JA, Kleber, ME, Guo, X, Wang, JJin, Auer, PL, Attia, JR, Yanek, LR, Ahluwalia, TS, Lahti, J, Venturini, C, Tanaka, T, Bielak, LF, Joshi, PK, Rocanin-Arjo, A, Kolcic, I, Navarro, P, Rose, LM, Oldmeadow, C, Riess, H, Mazur, J, Basu, S, Goel, A, Yang, Q, Ghanbari, M, Willemsen, G, Rumley, A, Fiorillo, E, de Craen, AJM, Grotevendt, A, Scott, R, Taylor, KD, Delgado, GE, Yao, J, Kifley, A, Kooperberg, C, Qayyum, R, Lopez, LM, Berentzen, TL, Räikkönen, K, Mangino, M, Bandinelli, S, Peyser, PA, Wild, S, Trégouët, D-A, Wright, AF, Marten, J, Zemunik, T, Morrison, AC, Sennblad, B, Tofler, G, de Maat, MPM, de Geus, EJC, Lowe, GD, Zoledziewska, M, Sattar, N, Binder, H, Völker, U, Waldenberger, M, Khaw, K-T, McKnight, B, Huang, J, Jenny, NS, Holliday, EG, Qi, L, Mcevoy, MG, Becker, DM, Starr, JM, Sarin, A-P, Hysi, PG, Hernandez, DG, Jhun, MA, Campbell, H, Hamsten, A, Rivadeneira, F, McArdle, WL, P Slagboom, E, Zeller, T, Koenig, W, Psaty, BM, Haritunians, T, Liu, J, Palotie, A, Uitterlinden, AG, Stott, DJ, Hofman, A, Franco, OH, Polasek, O, Rudan, I, Morange, P-E, Wilson, JF, Kardia, SLR, Ferrucci, L, Spector, TD, Eriksson, JG, Hansen, T, Deary, IJ, Becker, LC, Scott, RJ, Mitchell, P, März, W, Wareham, NJ, Peters, A, Greinacher, A, Wild, PS, J Jukema, W, Boomsma, DI, Hayward, C, Cucca, F, Tracy, R, Watkins, H, Reiner, AP, Folsom, AR, Ridker, PM, O'Donnell, CJ, Smith, NL, Strachan, DP, Dehghan, A |
Journal | Hum Mol Genet |
Volume | 25 |
Issue | 2 |
Pagination | 358-70 |
Date Published | 2016 Jan 15 |
ISSN | 1460-2083 |
Abstract | <p>Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.</p> |
DOI | 10.1093/hmg/ddv454 |
Alternate Journal | Hum. Mol. Genet. |
PubMed ID | 26561523 |
PubMed Central ID | PMC4715256 |
Grant List | 068545/Z/02 / / Wellcome Trust / United Kingdom 076113/B/04/Z / / Wellcome Trust / United Kingdom 1RC2 MH089951 / MH / NIMH NIH HHS / United States BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom CA047988 / CA / NCI NIH HHS / United States CA137088 / CA / NCI NIH HHS / United States CZB/4/505 / / Chief Scientist Office / United Kingdom DK063491 / DK / NIDDK NIH HHS / United States ETM/55 / / Chief Scientist Office / United Kingdom FP7/2007-2013 / / Wellcome Trust / United Kingdom G0000934 / / Medical Research Council / United Kingdom G1000143 / / Medical Research Council / United Kingdom G1001799 / / Medical Research Council / United Kingdom HL043851 / HL / NHLBI NIH HHS / United States HL071025-01A1 / HL / NHLBI NIH HHS / United States HL080467 / HL / NHLBI NIH HHS / United States HL087660 / HL / NHLBI NIH HHS / United States HL097698 / HL / NHLBI NIH HHS / United States HL100245 / HL / NHLBI NIH HHS / United States HL59684 / HL / NHLBI NIH HHS / United States K24 DK080140 / DK / NIDDK NIH HHS / United States M01-RR000052 / RR / NCRR NIH HHS / United States MC_PC_U127561128 / / Medical Research Council / United Kingdom MC_U106179471 / / Medical Research Council / United Kingdom MC_UU_12015/1 / / Medical Research Council / United Kingdom MH081802 / MH / NIMH NIH HHS / United States MR/K026992/1 / / Medical Research Council / United Kingdom MR/N01104X/1 / / Medical Research Council / United Kingdom NR0224103 / NR / NINR NIH HHS / United States NS017950 / NS / NINDS NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01AG023629 / AG / NIA NIH HHS / United States R01D0042157-01A / / PHS HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States R01HL103612 / HL / NHLBI NIH HHS / United States R01HL105756 / HL / NHLBI NIH HHS / United States R01HL120393 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States R25CA094880 / CA / NCI NIH HHS / United States RC2 HL-102924 / HL / NHLBI NIH HHS / United States U01 HL72518 / HL / NHLBI NIH HHS / United States U01-HG005152 / HG / NHGRI NIH HHS / United States U01DK062418 / DK / NIDDK NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States U24 MH068457-06 / MH / NIMH NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States / / Cancer Research UK / United Kingdom / / Department of Health / United Kingdom / / British Heart Foundation / United Kingdom / / Arthritis Research UK / United Kingdom / / Intramural NIH HHS / United States |