Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels

Genome Netherlands Consortium, Elisabeth M. van Leeuwen, Lennart C. Karssen, Joris Deelen, Aaron Isaacs, Carolina Medina-Gomez, Hamdi Mbarek, Alexandros Kanterakis, Stella Trompet, Iris Postmus, Niek Verweij, David J. van Enckevort, Jennifer E. Huffman, Charles C. White, Mary F. Feitosa, Traci M. Bartz, Ani Manichaikul, Peter K. Joshi, Gina M. Peloso, Patrick DeelenFreerk van Dijk, Gonneke Willemsen, Eco J. de Geus, Yuri Milaneschi, Brenda W. J. H. Penninx, Laurent C. Francioli, Androniki Menelaou, Sara L. Pulit, Fernando Rivadeneira, Albert Hofman, Ben A. Oostra, Oscar H. Franco, Irene Mateo Leach, Marian Beekman, Anton J. M. de Craen, Hae-Won Uh, Holly Trochet, Lynne J. Hocking, David J. Porteous, Naveed Sattar, Chris J. Packard, Brendan M. Buckley, Jennifer A. Brody, Joshua C. Bis, Harry Campbell, James F. Wilson, Caroline Hayward, Ozren Polasek, Veronique Vitart, Igor Rudan, Alan F. Wright

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number6065
Number of pages6
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 9 Mar 2015

Keywords / Materials (for Non-textual outputs)

  • WIDE ASSOCIATION
  • MUTATIONS
  • DISEASE

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