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 (∼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 × 10-4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to... Mehr ...

Verfasser: Leeuwen, E.M. (Elisa) van
Karssen, L.C. (Lennart)
Deelen, J. (Joris)
Isaacs, A. (Aaron)
Medina-Gomez, M.C. (Carolina)
Mbarek, H.
Kanterakis, A. (Alexandros)
Trompet, S. (Stella)
Postmus, D. (Douwe)
Verweij, N. (Niek)
Enckevort, D. (David) van
Huffman, J.E. (Jennifer)
White, C.C. (Charles)
Feitosa, M.F. (Mary Furlan)
Bartz, T.M. (Traci M.)
Manichaikul, A. (Ani)
Joshi, P.K. (Peter)
Peloso, G.M. (Gina)
Deelen, P. (Patrick)
Dijk, F. (Freerk) van
Willemsen, G.A.H.M. (Gonneke)
Geus, E.J.C. (Eco) de
Milaneschi, Y. (Yuri)
Penninx, B.W.J.H. (Brenda)
Francioli, L.C. (Laurent)
Menelaou, A. (Androniki)
Pulit, S.L. (Sara)
Rivadeneira Ramirez, F. (Fernando)
Hofman, A. (Albert)
Oostra, B.A. (Ben)
Franco, O.H. (Oscar)
Leach, I.M. (Irene Mateo)
Beekman, M. (Marian)
Craen, A.J. (Anton) de
Uh, H.-W. (Hae-Won)
Trochet, H. (Holly)
Hocking, L.J. (Lynne)
Porteous, D.J. (David J.)
Sattar, N. (Naveed)
Packard, C.J. (Chris J.)
Buckley, B.M. (Brendan M.)
Brody, J.A. (Jennifer A.)
Bis, J.C. (Joshua)
Rotter, J.I. (Jerome I.)
Mychaleckyj, J.C. (Josyf)
Campbell, H. (Harry)
Duan, Q. (Qing)
Lange, L.A. (Leslie)
Wilson, J.F. (James F)
Hayward, C. (Caroline)
Polasek, O. (Ozren)
Vitart, V. (Veronique)
Rudan, I. (Igor)
Wright, A. (Alan)
Rich, S.S. (Stephen S.)
Psaty, B.M. (Bruce)
Borecki, I.B. (Ingrid)
Kearney, P.M. (Patricia M.)
Stott, D.J. (David. J.)
Cupples, L.A. (Adrienne)
Jukema, J.W. (Jan Wouter)
Harst, P. (Pim) van der
Sijbrands, E.J.G. (Eric)
Hottenga, J.J. (Jouke Jan)
Uitterlinden, A.G. (André)
Swertz, M. (Morris)
Van Ommen, G.-J.B. (Gert-Jan B.)
Bakker, P.I.W. (Paul) de
Slagboom, P.E. (Eline)
Boomsma, D.I. (Dorret)
Wijmenga, C. (Cisca)
Duijn, C.M. (Cornelia) van
Dokumenttyp: Artikel
Erscheinungsdatum: 2015
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29199553
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://repub.eur.nl/pub/81633

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 (∼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 × 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 (βLDL-C =0.135, βTC =0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.