@article{556c3ac524bc4ac2ad210e4c9af367b4,
title = "Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels",
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 (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.",
keywords = "WIDE ASSOCIATION, MUTATIONS, DISEASE",
author = "{Genome Netherlands Consortium} and {van Leeuwen}, {Elisabeth M.} and Karssen, {Lennart C.} and Joris Deelen and Aaron Isaacs and Carolina Medina-Gomez and Hamdi Mbarek and Alexandros Kanterakis and Stella Trompet and Iris Postmus and Niek Verweij and {van Enckevort}, {David J.} and Huffman, {Jennifer E.} and White, {Charles C.} and Feitosa, {Mary F.} and Bartz, {Traci M.} and Ani Manichaikul and Joshi, {Peter K.} and Peloso, {Gina M.} and Patrick Deelen and {van Dijk}, Freerk and Gonneke Willemsen and {de Geus}, {Eco J.} and Yuri Milaneschi and Penninx, {Brenda W. J. H.} and Francioli, {Laurent C.} and Androniki Menelaou and Pulit, {Sara L.} and Fernando Rivadeneira and Albert Hofman and Oostra, {Ben A.} and Franco, {Oscar H.} and Leach, {Irene Mateo} and Marian Beekman and {de Craen}, {Anton J. M.} and Hae-Won Uh and Holly Trochet and Hocking, {Lynne J.} and Porteous, {David J.} and Naveed Sattar and Packard, {Chris J.} and Buckley, {Brendan M.} and Brody, {Jennifer A.} and Bis, {Joshua C.} and Harry Campbell and Wilson, {James F.} and Caroline Hayward and Ozren Polasek and Veronique Vitart and Igor Rudan and Wright, {Alan F.}",
note = "Date of Acceptance: 09/12/2014",
year = "2015",
month = mar,
day = "9",
doi = "10.1038/ncomms7065",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}