Author:
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.,Adrienne Cupples L.,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.
Abstract
Abstract
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 (β
LDL-C=0.135, β
TC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry