Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels
Nolte IM; Mychaleckyj JC; Campbell H; Sabo A; Padmanabhan S; Demissie S; Viikari JS; Mbarek H; Kahonen M; Hofman A; Wilson JG; Sijbrands EJ; de Craen AJM; Nikus K; Franco OH; Morrison A; Ripatti S; Joshi PK; Tayo BO; Evangelou E; Jukema JW; de Mutsert R; Gudnason V; Lehne B; Deelen J; van Duijn CM; Kooner JS; White CC; Scott WR; Raitakari OT; Kooner AS; Lehtimaki T; Rivadeneira F; Chambers JC; Forrester T; Trompet S; Boomsma DI; Wilson JF; Gansevoort RT; Smith AV; Verweij N; Huffman JE; Borecki IB; Snieder H; Milaneschi Y; Rice KM; Zhang WH; Vitart V; Campbell A; Hocking LJ; Rudan I; Willemsen G; Elliott P; Salomaa V; Rotter JI; Rich SS; Brody JA; Segura-Lepe MP; van der Harst P; Tan ST; Boerwinkle E; Psaty BM; Cooper RS; Li-Gao RF; Cupples LA; van der Laan SW; Penninx BWJH; de Ruijter HM; Duan Q; Isaacs A; Harris T; Manichaikul A; McKenzie CA; Swertz M; Feitosa MF; van Leeuwen EM; Lyytikainen LP; Pasterkamp G; Oldehinkel AJ; Kolcic I; Marten J; Lange LA; de Geus EJ; Mook-Kanamori DO; van der Most PJ; Zemunik T; Navarro P; Surakka I; Bis JC; van Dijk KW; Uitterlinden AG; Hayward C; Polasek O; van Klinken JB; Dehghan A; Arking DE; Slagboom PE; Ford I
Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels
Nolte IM
Mychaleckyj JC
Campbell H
Sabo A
Padmanabhan S
Demissie S
Viikari JS
Mbarek H
Kahonen M
Hofman A
Wilson JG
Sijbrands EJ
de Craen AJM
Nikus K
Franco OH
Morrison A
Ripatti S
Joshi PK
Tayo BO
Evangelou E
Jukema JW
de Mutsert R
Gudnason V
Lehne B
Deelen J
van Duijn CM
Kooner JS
White CC
Scott WR
Raitakari OT
Kooner AS
Lehtimaki T
Rivadeneira F
Chambers JC
Forrester T
Trompet S
Boomsma DI
Wilson JF
Gansevoort RT
Smith AV
Verweij N
Huffman JE
Borecki IB
Snieder H
Milaneschi Y
Rice KM
Zhang WH
Vitart V
Campbell A
Hocking LJ
Rudan I
Willemsen G
Elliott P
Salomaa V
Rotter JI
Rich SS
Brody JA
Segura-Lepe MP
van der Harst P
Tan ST
Boerwinkle E
Psaty BM
Cooper RS
Li-Gao RF
Cupples LA
van der Laan SW
Penninx BWJH
de Ruijter HM
Duan Q
Isaacs A
Harris T
Manichaikul A
McKenzie CA
Swertz M
Feitosa MF
van Leeuwen EM
Lyytikainen LP
Pasterkamp G
Oldehinkel AJ
Kolcic I
Marten J
Lange LA
de Geus EJ
Mook-Kanamori DO
van der Most PJ
Zemunik T
Navarro P
Surakka I
Bis JC
van Dijk KW
Uitterlinden AG
Hayward C
Polasek O
van Klinken JB
Dehghan A
Arking DE
Slagboom PE
Ford I
BMJ PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042715591
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.
Kokoelmat
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