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 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 WH; Mbarek H; Li-Gao RF; Trompet S; Verweij N; Evangelou E; Lyytikainen LP; 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 ST; 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; Slagboom PE; Cooper RS; Kahonen M; Lehtimaki T; Elliott P; van der Harst P; Jukema JW; Mook-Kanamori DO; Boomsma DI; Chambers JC; Swertz M; Ripatti S; van Dijk KW; Vitart V; Polasek O; Hayward C; Wilson JG; Wilson JF; Gudnason V; Rich SS; Psaty BM; Borecki IB; Boerwinkle E; Rotter JI; Cupples LA; van Duijn CM
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 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 WH
Mbarek H
Li-Gao RF
Trompet S
Verweij N
Evangelou E
Lyytikainen LP
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 ST
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
Slagboom PE
Cooper RS
Kahonen M
Lehtimaki T
Elliott P
van der Harst P
Jukema JW
Mook-Kanamori DO
Boomsma DI
Chambers JC
Swertz M
Ripatti S
van Dijk KW
Vitart V
Polasek O
Hayward C
Wilson JG
Wilson JF
Gudnason V
Rich SS
Psaty BM
Borecki IB
Boerwinkle E
Rotter JI
Cupples LA
van Duijn CM
Katso/Avaa
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BMJ PUBLISHING GROUP
doi:10.1136/jmedgenet-2015-103439
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042715591
Tiivistelmä
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 similar to 60 000 individuals in the discovery stage and similar to 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.
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