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

P.S. de Vries, D.I. Chasman, M. Sabater-Lleal, M.H. Chen, J.E. Huffman, M. Steri, W. Tang, A. Teumer, R.E. Marioni, V. Grossmann, J.J. Hottenga, G. Willemsen, E.J.C. de Geus, D.I. Boomsma, F. Cucca, R. Tracy, H. Watkins, A.P. Reiner, A.R. Folsom, P.M. RidkerC.J. O'Donnell, N.L. Smith, D.P. Strachan, A. Dehghan

Research output: Contribution to JournalArticleAcademicpeer-review

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 indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere 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.
Original languageEnglish
Pages (from-to)358-370
JournalHuman Molecular Genetics
Volume25
Issue number2
DOIs
Publication statusPublished - 2016

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