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

de Vries, P. et al. (2016) A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration. Human Molecular Genetics, 25(2), pp. 358-370. (doi:10.1093/hmg/ddv454) (PMID:26561523)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Professor David J and Sattar, Professor Naveed
Authors: de Vries, P., Chasman, D., Sabater-Lleal, M., Chen, M.-H., Huffman, J. E., Steri, M., Tang, W., Teumer, A., Marioni, R. E., Grossmann, V., Hottenga, J. J., Trompet, S., Müller-Nurasyid, M., Zhao, J. H., Brody, J. A., Kleber, M. E., Guo, X., Wang, J. J., Auer, P. L., Attia, J. R., Yanek, L. R., Ahluwalia, T. S., Lahti, J., Venturini, C., Tanaka, T., Bielak, L. F., Joshi, P. K., Rocanin-Arjo, A., Kolcic, I., Navarro, P., Rose, L. M., Oldmeadow, C., Riess, H., Mazur, J., Basu, S., Goel, A., Yang, Q., Ghanbari, M., Willemsen, G., Rumley, A., Fiorillo, E., de Craen, A. J. M., Grotevendt, A., Scott, R., Taylor, K. D., Delgado, G. E., Yao, J., Kifley, A., Kooperberg, C., Qayyum, R., Lopez, L. M., Berentzen, T. L., Räikkönen, K., Mangino, M., Bandinelli, S., Peyser, P. A., Wild, S., Trégouët, D.-A., Wright, A. F., Marten, J., Zemunik, T., Morrison, A. C., Sennblad, B., Tofler, G., de Maat, M. P. M., de Geus, E. J. C., Lowe, G. D., Zoledziewska, M., Sattar, N., Binder, H., Völker, U., Waldenberger, M., Khaw, K.-T., Mcknight, B., Huang, J., Jenny, N. S., Holliday, E. G., Qi, L., Mcevoy, M. G., Becker, D. M., Starr, J. M., Sarin, A.-P., Hysi, P. G., Hernandez, D. G., Jhun, M. A., Campbell, H., Hamsten, A., Rivadeneira, F., Mcardle, W. L., Slagboom, P. E., Zeller, T., Koenig, W., Psaty, B. M., Haritunians, T., Liu, J., Palotie, A., Uitterlinden, A. G., Stott, D. J., Hofman, A., Franco, O. H., Polasek, O., Rudan, I., Morange, P.-E., Wilson, J. F., Kardia, S. L. R., Ferrucci, L., Spector, T. D., Eriksson, J. G., Hansen, T., Deary, I. J., Becker, L. C., Scott, R. J., Mitchell, P., März, W., Wareham, N. J., Peters, A., Greinacher, A., Wild, P. S., Jukema, J. W., Boomsma, D. I., Hayward, C., Cucca, F., Tracy, R., Watkins, H., Reiner, A. P., Folsom, A. R., Ridker, P. M., O'Donnell, C. J., Smith, N. L., Strachan, D. P., and Dehghan, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Human Molecular Genetics
Publisher:Oxford University Press
ISSN:0964-6906
ISSN (Online):1460-2083
Published Online:10 November 2015

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