TY - JOUR AB - 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 ∼60000 individuals in the discovery stage and ∼90000 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. AU - van,Leeuwen EM AU - Sabo,A AU - Bis,JC AU - Huffman,JE AU - Manichaikul,A AU - Smith,AV AU - Feitosa,MF AU - Demissie,S AU - Joshi,PK AU - Duan,Q AU - Marten,J AU - van,Klinken JB AU - Surakka,I AU - Nolte,IM AU - Zhang,W AU - Mbarek,H AU - Li-Gao,R AU - Trompet,S AU - Verweij,N AU - Evangelou,E AU - Lyytikäinen,LP AU - Tayo,BO AU - Deelen,J AU - van,der Most PJ AU - van,der Laan SW AU - Arking,DE AU - Morrison,A AU - Dehghan,A AU - Franco,OH AU - Hofman,A AU - Rivadeneira,F AU - Sijbrands,EJ AU - Uitterlinden,AG AU - Mychaleckyj,JC AU - Campbell,A AU - Hocking,LJ AU - Padmanabhan,S AU - Brody,JA AU - Rice,KM AU - White,CC AU - Harris,T AU - Isaacs,A AU - Campbell,H AU - Lange,LA AU - Rudan,I AU - Kolcic,I AU - Navarro,P AU - Zemunik,T AU - Salomaa,V AU - LifeLines,Cohort Study AU - Kooner,AS AU - Kooner,JS AU - Lehne,B AU - Scott,WR AU - Tan,ST AU - de,Geus EJ AU - Milaneschi,Y AU - Penninx,BW AU - Willemsen,G AU - de,Mutsert R AU - Ford,I AU - Gansevoort,RT AU - Segura-Lepe,MP AU - Raitakari,OT AU - Viikari,JS AU - Nikus,K AU - Forrester,T AU - McKenzie,CA AU - de,Craen AJ AU - de,Ruijter HM AU - Pasterkamp,G AU - Snieder,H AU - Oldehinkel,AJ AU - Slagboom,PE AU - Cooper,RS AU - Kähönen,M AU - Lehtimäki,T AU - Elliott,P AU - van,der Harst P AU - Jukema,JW AU - Mook-Kanamori,DO AU - Boomsma,DI AU - Chambers,JC AU - Swertz,M AU - Ripatti,S AU - Willems,van Dijk K AU - Vitart,V AU - Polasek,O AU - Hayward,C AU - Wilson,JG AU - Wilson,JF AU - Gudnason,V AU - Rich,SS AU - Psaty,BM AU - Borecki,IB AU - Boerwinkle,E AU - Rotter,JI AU - Cupples,LA AU - van,Duijn CM DO - 10.1136/jmedgenet-2015-103439 EP - 449 PY - 2016/// SN - 1468-6244 SP - 441 TI - Meta-analysis of 49549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels T2 - Journal of Medical Genetics UR - http://dx.doi.org/10.1136/jmedgenet-2015-103439 UR - http://hdl.handle.net/10044/1/32667 VL - 53 ER -