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 p... Mehr ...

Volltext
Verfasser: van Leeuwen, Elisabeth M.
Karssen, Lennart C.
Deelen, Joris
Isaacs, Aaron
Medina-Gomez, Carolina
Mbarek, Hamdi
Kanterakis, Alexandros
Trompet, Stella
Postmus, Iris
Verweij, Niek
van Enckevort, David J.
Huffman, Jennifer E.
White, Charles C.
Feitosa, Mary F.
Bartz, Traci M.
Manichaikul, Ani
Joshi, Peter K.
Peloso, Gina M.
Deelen, Patrick
van Dijk, Freerk
Willemsen, Gonneke
de Geus, Eco J.
Milaneschi, Yuri
Penninx, Brenda W. J. H.
Francioli, Laurent C.
Menelaou, Androniki
Pulit, Sara L.
Rivadeneira, Fernando
Hofman, Albert
Oostra, Ben A.
Franco, Oscar H.
Leach, Irene Mateo
Beekman, Marian
de Craen, Anton J. M.
Uh, Hae-Won
Trochet, Holly
Hocking, Lynne J.
Porteous, David J.
Sattar, Naveed
Packard, Chris J.
Buckley, Brendan M.
Brody, Jennifer A.
Bis, Joshua C.
Rotter, Jerome I.
Mychaleckyj, Josyf C.
Campbell, Harry
Duan, Qing
van der Harst, Pim
Swertz, Morris A.
Wijmenga, Cisca
Dokumenttyp: Artikel
Erscheinungsdatum: 2015
Reihe/Periodikum: van Leeuwen , E M , Karssen , L C , Deelen , J , Isaacs , A , Medina-Gomez , C , Mbarek , H , Kanterakis , A , Trompet , S , Postmus , I , Verweij , N , van Enckevort , D J , Huffman , J E , White , C C , Feitosa , M F , Bartz , T M , Manichaikul , A , Joshi , P K , Peloso , G M , Deelen , P , van Dijk , F , Willemsen , G , de Geus , E J , Milaneschi , Y , Penninx , B W J H , Francioli , L C , Menelaou , A , Pulit , S L , Rivadeneira , F , Hofman , A , Oostra , B A , Franco , O H , Leach , I M , Beekman , M , de Craen , A J M , Uh , H-W , Trochet , H , Hocking , L J , Porteous , D J , Sattar , N , Packard , C J , Buckley , B M , Brody , J A , Bis , J C , Rotter , J I , Mychaleckyj , J C , Campbell , H , Duan , Q , van der Harst , P , Swertz , M A , Wijmenga , C & Genome Netherlands Consortium 2015 , ' Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels ' , Nature Communications , vol. 6 , 6065 . https://doi.org/10.1038/ncomms7065
Schlagwörter: WIDE ASSOCIATION / MUTATIONS / DISEASE
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-26825812
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://hdl.handle.net/11370/835f1558-c1b5-4c6e-a4fe-4821f72ec247

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.