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: 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
Lange, Leslie A.
Wilson, James F.
Hayward, Caroline
Polasek, Ozren
Vitart, Veronique
Rudan, Igor
Wright, Alan F.
Rich, Stephen S.
Psaty, Bruce M.
Borecki, Ingrid B.
Kearney, Patricia M.
Stott, David J.
Cupples, L. Adrienne
Jukema, J. Wouter
Van Der Harst, Pim
Sijbrands, Eric J.
Hottenga, Jouke Jan
Uitterlinden, Andre G.
Swertz, Morris A.
Van Ommen, Gert Jan B
De Bakker, Paul I W
Eline Slagboom, P.
Boomsma, Dorret I.
Wijmenga, Cisca
Van Duijn, Cornelia M.
Neerincx, Pieter B T
Elbers, Clara C.
Palamara, Pier Francesco
Peer, Itsik
Abdellaoui, Abdel
Kloosterman, Wigard P.
Van Oven, Mannis
Vermaat, Martijn
Li, Mingkun
Laros, Jeroen F J
Stoneking, Mark
De Knijff, Peter
Kayser, Manfred
Veldink, Jan H.
Van Den Berg, Leonard H.
Byelas, Heorhiy
Den Dunnen, Johan T.
Dijkstra, Martijn
Amin, Najaf
Van Der Velde, K. Joeri
Van Setten, Jessica
Kattenberg, Mathijs
Van Schaik, Barbera D C
Bot, Jan
Nijman, Isaäc J.
Mei, Hailiang
Koval, Vyacheslav
Ye, Kai
Lameijer, Eric Wubbo
Moed, Matthijs H.
Hehir-Kwa, Jayne Y.
Handsaker, Robert E.
Sunyaev, Shamil R.
Sohail, Mashaal
Hormozdiari, Fereydoun
Marschall, Tobias
Schönhuth, Alexander
Guryev, Victor
Suchiman, H. Eka D
Wolffenbuttel, Bruce H.
Platteel, Mathieu
Pitts, Steven J.
Potluri, Shobha
Cox, David R.
Li, Qibin
Li, Yingrui
Du, Yuanping
Chen, Ruoyan
Cao, Hongzhi
Li, Ning
Cao, Sujie
Wang, Jun
Bovenberg, Jasper A.
de Bakker, Paul I W
Dokumenttyp: Artikel
Erscheinungsdatum: 2015
Schlagwörter: General Biochemistry / Genetics and Molecular Biology / General Chemistry / General Physics and Astronomy
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27610515
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://dspace.library.uu.nl/handle/1874/333051

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.