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

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; Lyytikainen, 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; Lifelines Cohort Study; Kooner, A. S.; Kooner, J. S.; Lehne, B; Scott, W. R.; Tan, S. T.; de Geus, E. J.; Milaneschi, Y; Penninx, B. W.; 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.; de Ruijter, H. M.; Pasterkamp, G; Snieder, H; Oldehinkel, A. J.; Slagboom, P. E.; Cooper, R. S.; Kahonen, M.; Lehtimaki, 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.; van Duijn, C. M.
Article Title: Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels
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 approximately 60 000 individuals in the discovery stage and approximately 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.
Journal Title: Journal of medical genetics
ISSN: 1468-6244; 0022-2593
Publisher: Unknown  
Date Published: 2016
Language: ENG
Notes: LR: 20160527; CI: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to; GR: CZD/16/6/4/Chief Scientist Office/United Kingdom; JID: 2985087R; OTO: NOTNLM; 2015/08/04 [received]; 2015/11/23 [accepted]; aheadofprint