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. Ridker; C.J. O'Donnell; N.L. Smith; D.P. Strachan; A. Dehghan

doi:10.1093/hmg/ddv454

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 Journal › Article › Academic › peer-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 language	English
Pages (from-to)	358-370
Journal	Human Molecular Genetics
Volume	25
Issue number	2
DOIs	https://doi.org/10.1093/hmg/ddv454
Publication status	Published - 2016

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de Vries, P. S., Chasman, D. I., Sabater-Lleal, M., Chen, M. H., Huffman, J. E., Steri, M., Tang, W., Teumer, A., Marioni, R. E., Grossmann, V., Hottenga, J. J., Willemsen, G., de Geus, E. J. C., Boomsma, D. I., Cucca, F., Tracy, R., Watkins, H., Reiner, A. P., Folsom, A. R., ... Dehghan, A. (2016). A meta-analysis of 120,246 individuals identifies 18 new loci for fibrinogen concentration. Human Molecular Genetics, 25(2), 358-370. https://doi.org/10.1093/hmg/ddv454

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

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.",

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

year = "2016",

doi = "10.1093/hmg/ddv454",

language = "English",

volume = "25",

pages = "358--370",

journal = "Human Molecular Genetics",

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de Vries, PS, Chasman, DI, Sabater-Lleal, M, Chen, MH, Huffman, JE, Steri, M, Tang, W, Teumer, A, Marioni, RE, Grossmann, V, Hottenga, JJ, Willemsen, G, de Geus, EJC , Boomsma, DI, Cucca, F, Tracy, R, Watkins, H, Reiner, AP, Folsom, AR, Ridker, PM, O'Donnell, CJ, Smith, NL, Strachan, DP & Dehghan, A 2016, 'A meta-analysis of 120,246 individuals identifies 18 new loci for fibrinogen concentration', Human Molecular Genetics, vol. 25, no. 2, pp. 358-370. https://doi.org/10.1093/hmg/ddv454

TY - JOUR

T1 - A meta-analysis of 120,246 individuals identifies 18 new loci for fibrinogen concentration

AU - de Vries, P.S.

AU - Chasman, D.I.

AU - Sabater-Lleal, M.

AU - Chen, M.H.

AU - Huffman, J.E.

AU - Steri, M.

AU - Tang, W.

AU - Teumer, A.

AU - Marioni, R.E.

AU - Grossmann, V.

AU - Hottenga, J.J.

AU - Willemsen, G.

AU - de Geus, E.J.C.

AU - Boomsma, D.I.

AU - Cucca, F.

AU - Tracy, R.

AU - Watkins, H.

AU - Reiner, A.P.

AU - Folsom, A.R.

AU - Ridker, P.M.

AU - O'Donnell, C.J.

AU - Smith, N.L.

AU - Strachan, D.P.

AU - Dehghan, A.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1093/hmg/ddv454

DO - 10.1093/hmg/ddv454

M3 - Article

SN - 0964-6906

VL - 25

SP - 358

EP - 370

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 2

ER -

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

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