Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels

van Leeuwen, E. M. et al. (2016) Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels. Journal of Medical Genetics, 53(7), pp. 441-449. (doi: 10.1136/jmedgenet-2015-103439) (PMID:27036123) (PMCID:PMC4941146)

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Abstract

Background: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods: We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. Results: Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. Conclusions: This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ford, Professor Ian and Padmanabhan, Professor Sandosh
Authors: van Leeuwen, E. M., Sabo, A., Bis, J. C., Huffman, J. E., Manichaikul, A., Smith, A. V., Feitosa, M. F., Demissie, S., Joshi, P. K., Duan, Q., Marten, J., van Klinken, J. B., Surakka, I., Nolte, I. M., Zhang, W., Mbarek, H., Li-Gao, R., Trompet, S., Verweij, N., Evangelou, E., Lyytikäinen, L.-P., Tayo, B. O., Deelen, J., van der Most, P. J., van der Laan, S. W., Arking, D. E., Morrison, A., Dehghan, A., Franco, O. H., Hofman, A., Rivadeneira, F., Sijbrands, E. J., Uitterlinden, A. G., Mychaleckyj, J. C., Campbell, A., Hocking, L. J., Padmanabhan, S., Brody, J. A., Rice, K. M., White, C. C., Harris, T., Isaacs, A., Campbell, H., Lange, L. A., Rudan, I., Kolcic, I., Navarro, P., Zemunik, T., Salomaa, V., Kooner, A. S., Kooner, J. S., Lehne, B., Scott, W. R., Tan, S.-T., de Geus, E. J., Milaneschi, Y., Penninx, B. W.J.H., Willemsen, G., de Mutsert, R., Ford, I., Gansevoort, R. T., Segura-Lepe, M. P., Raitakari, O. T., Viikari, J. S., Nikus, K., Forrester, T., McKenzie, C. A., de Craen, A. J.M., de Ruijter, H. M., Pasterkamp, G., Snieder, H., Oldehinkel, A. J., Slagboom, P. E., Cooper, R. S., Kähönen, M., Lehtimäki, T., Elliott, P., van der Harst, P., Jukema, J. W., Mook-Kanamori, D. O., Boomsma, D. I., Chambers, J. C., Swertz, M., Ripatti, S., Willems van Dijk, K., Vitart, V., Polasek, O., Hayward, C., Wilson, J. G., Wilson, J. F., Gudnason, V., Rich, S. S., Psaty, B. M., Borecki, I. B., Boerwinkle, E., Rotter, J. I., Cupples, L. A., and van Duijn, C. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Journal of Medical Genetics
Publisher:BMJ Publishing Group
ISSN:0022-2593
ISSN (Online):1468-6244
Published Online:01 April 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Journal of Medical Genetics 53(7): 441-449
Publisher Policy:Reproduced under a Creative Commons License

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