Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (similar to 35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value < 6.61 x 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is... Mehr ...

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Verfasser: Leeuwen, Elisa
Karssen, Lennart
Deelen, J
Isaacs, Aaron
Medina-Gomez, C
Mbarek, H
Kanterakis, A
Trompet, S
Postmus, I
Verweij, N (Niek)
van Enckevort, DJ
Huffman, JE
White, CC
Feitosa, MF
Bartz, TM
Manichaikul, A
Joshi, PK
Peloso, GM
Deelen, P
Dijk, Femke
Willemsen, G
de Geus, EJ
Milaneschi, Y
Penninx, BWJH
Francioli, LC
Menelaou, A
Pulit, SL
Rivadeneira, Fernando
Hofman, Bert
Oostra, Ben
Franco Duran, OH
Leach, IM
Beekman, M
de Craen, AJM
Uh, HW
Trochet, H
Hocking, LJ
Porteous, DJ
Sattar, N
Packard, CJ
Buckley, BM
Brody, JA
Bis, JC
Rotter, JI
Mychaleckyj, JC
Campbell, H
Duan, Q
Lange, LA
Wilson, JF
Hayward, C
Dokumenttyp: Artikel
Erscheinungsdatum: 2015
Reihe/Periodikum: Leeuwen , E , Karssen , L , Deelen , J , Isaacs , A , Medina-Gomez , C , Mbarek , H , Kanterakis , A , Trompet , S , Postmus , I , Verweij , N , van Enckevort , DJ , Huffman , JE , White , CC , Feitosa , MF , Bartz , TM , Manichaikul , A , Joshi , PK , Peloso , GM , Deelen , P , Dijk , F , Willemsen , G , de Geus , EJ , Milaneschi , Y , Penninx , BWJH , Francioli , LC , Menelaou , A , Pulit , SL , Rivadeneira , F , Hofman , B , Oostra , B , Franco Duran , OH , Leach , IM , Beekman , M , de Craen , AJM , Uh , HW , Trochet , H , Hocking , LJ , Porteous , DJ , Sattar , N , Packard , CJ , Buckley , BM , Brody , JA , Bis , JC , Rotter , JI , Mychaleckyj , JC , Campbell , H , Duan , Q , Lange , LA , Wilson , JF , Hayward , C , Polasek , O , Vitart , V , Rudan , I , Wright , AF , Rich , SS , Psaty , BM , Borecki , IB , Kearney , PM , Stott , DJ , Cupples , LA , Jukema , JW , van der Harst , P , Sijbrands , E J G , Hottenga , JJ , Uitterlinden , A , Swertz , MA , van Ommen , GJB , de Bakker , PIW , Slagboom , PE , Boomsma , DI , Wijmenga , C & Duijn , C 2015 , ' Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels ' , Nature Communications , vol. 6 . https://doi.org/10.1038/ncomms7065
Sprache: unknown
Permalink: https://search.fid-benelux.de/Record/base-26842047
Datenquelle: BASE; Originalkatalog
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Link(s) : https://pure.eur.nl/en/publications/e163092a-1fc2-4b1e-817e-646e92add8e8

Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (similar to 35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value < 6.61 x 10(-4)), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (beta(LDL-C) = 0.135, beta(TC) = 0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.