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

TitleMeta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels.
Publication TypeJournal Article
Year of Publication2016
Authorsvan Leeuwen, EM, Sabo, A, Bis, JC, Huffman, JE, Manichaikul, A, Smith, AV, Feitosa, MF, Demissie, S, Joshi, PK, Duan, Q, Marten, J, van Klinken, JB, Surakka, I, Nolte, IM, Zhang, W, Mbarek, H, Li-Gao, R, Trompet, S, Verweij, N, Evangelou, E, Lyytikäinen, L-P, Tayo, BO, Deelen, J, van der Most, PJ, van der Laan, SW, Arking, DE, Morrison, A, Dehghan, A, Franco, OH, Hofman, A, Rivadeneira, F, Sijbrands, EJ, Uitterlinden, AG, Mychaleckyj, JC, Campbell, A, Hocking, LJ, Padmanabhan, S, Brody, JA, Rice, KM, White, CC, Harris, T, Isaacs, A, Campbell, H, Lange, LA, Rudan, I, Kolcic, I, Navarro, P, Zemunik, T, Salomaa, V, Kooner, AS, Kooner, JS, Lehne, B, Scott, WR, Tan, S-T, de Geus, EJ, Milaneschi, Y, Penninx, BWJH, Willemsen, G, de Mutsert, R, Ford, I, Gansevoort, RT, Segura-Lepe, MP, Raitakari, OT, Viikari, JS, Nikus, K, Forrester, T, McKenzie, CA, de Craen, AJM, de Ruijter, HM, Pasterkamp, G, Snieder, H, Oldehinkel, AJ, P Slagboom, E, Cooper, RS, Kähönen, M, Lehtimäki, T, Elliott, P, van der Harst, P, J Jukema, W, Mook-Kanamori, DO, Boomsma, DI, Chambers, JC, Swertz, M, Ripatti, S, van Dijk, KWillems, Vitart, V, Polasek, O, Hayward, C, Wilson, JG, Wilson, JF, Gudnason, V, Rich, SS, Psaty, BM, Borecki, IB, Boerwinkle, E, Rotter, JI, Cupples, AL, van Duijn, CM
Corporate/Institutional AuthorsLifeLines Cohort Study,, CHARGE Lipids Working Group
JournalJ Med Genet
Date Published2016 Jul
Abstract<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.</p>
Alternate JournalJ. Med. Genet.
PubMed ID27036123
PubMed Central IDPMC4941146
Grant ListCZD/16/6/4 / / Chief Scientist Office / United Kingdom
P30 DK063491 / DK / NIDDK NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States