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

Hum Mol Genet. 2016 Jan 15;25(2):358-70. doi: 10.1093/hmg/ddv454. Epub 2015 Nov 10.

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.

Publication types

  • Meta-Analysis
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • European Continental Ancestry Group / genetics
  • Female
  • Fibrinogen / analysis*
  • Fibrinogen / genetics
  • Genetic Loci*
  • Genome-Wide Association Study
  • Humans
  • INDEL Mutation
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Fibrinogen

Grant support