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A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

TitleA meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.
Publication TypeJournal Article
Year of Publication2016
Authorsde Vries PS, Chasman DI, Sabater-Lleal M, et al.
Secondary AuthorsDehghan A
JournalHum Mol Genet
Volume25
Issue2
Pagination358-70
Date Published2016 Jan 15
ISSN1460-2083
KeywordsAdult, Aged, Aged, 80 and over, European Continental Ancestry Group, Female, Fibrinogen, Genetic Loci, Genome-Wide Association Study, Humans, INDEL Mutation, Male, Middle Aged, Polymorphism, Single Nucleotide
Abstract

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.

DOI10.1093/hmg/ddv454
Alternate JournalHum Mol Genet
PubMed ID26561523
PubMed Central IDPMC4715256
Grant ListETM/55 / / Chief Scientist Office / United Kingdom
UL1RR025005 / RR / NCRR NIH HHS / United States
CZB/4/505 / / Chief Scientist Office / United Kingdom
G1001799 / / Medical Research Council / United Kingdom
UL1TR000124 / TR / NCATS NIH HHS / United States
/ / British Heart Foundation / United Kingdom
HL59684 / HL / NHLBI NIH HHS / United States
HL043851 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HL071025-01A1 / HL / NHLBI NIH HHS / United States
1RC2 MH089951 / MH / NIMH NIH HHS / United States
HL097698 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
K24 DK080140 / DK / NIDDK NIH HHS / United States
CA137088 / CA / NCI NIH HHS / United States
G1000143 / / Medical Research Council / United Kingdom
/ / Department of Health / United Kingdom
M01-RR000052 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
MC_UU_12015/1 / / Medical Research Council / United Kingdom
R01 HL119443 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
MC_U106179471 / / Medical Research Council / United Kingdom
CA047988 / CA / NCI NIH HHS / United States
MR/N01104X/1 / / Medical Research Council / United Kingdom
P30 DK063491 / DK / NIDDK NIH HHS / United States
RC2 HL-102924 / HL / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
/ / Cancer Research UK / United Kingdom
R01HL087641 / HL / NHLBI NIH HHS / United States
MC_PC_U127592696 / / Medical Research Council / United Kingdom
FP7/2007-2013 / / Wellcome Trust / United Kingdom
HL087660 / HL / NHLBI NIH HHS / United States
G0401527 / / Medical Research Council / United Kingdom
R01HL105756 / HL / NHLBI NIH HHS / United States
R25CA094880 / CA / NCI NIH HHS / United States
NR0224103 / NR / NINR NIH HHS / United States
R01D0042157-01A / / PHS HHS / United States
U01 HL72518 / HL / NHLBI NIH HHS / United States
MC_PC_U127561128 / / Medical Research Council / United Kingdom
UM1 CA182913 / CA / NCI NIH HHS / United States
R01AG023629 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
/ / Arthritis Research UK / United Kingdom
HL100245 / HL / NHLBI NIH HHS / United States
R01HL087652 / HL / NHLBI NIH HHS / United States
HL080467 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
NS017950 / NS / NINDS NIH HHS / United States
U24 MH068457-06 / MH / NIMH NIH HHS / United States
U01DK062418 / DK / NIDDK NIH HHS / United States
068545/Z/02 / / Wellcome Trust / United Kingdom
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
U01HL080295 / HL / NHLBI NIH HHS / United States
U01-HG005152 / HG / NHGRI NIH HHS / United States
R01HL103612 / HL / NHLBI NIH HHS / United States
076113/B/04/Z / / Wellcome Trust / United Kingdom
G0000934 / / Medical Research Council / United Kingdom
R01HL120393 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
MH081802 / MH / NIMH NIH HHS / United States