TY - JOUR
T1 - Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
AU - The Genome of the Netherlands Consortium
AU - Van Leeuwen, Elisabeth M.
AU - Karssen, Lennart C.
AU - Deelen, Joris
AU - Isaacs, Aaron
AU - Medina-Gomez, Carolina
AU - Mbarek, Hamdi
AU - Kanterakis, Alexandros
AU - Trompet, Stella
AU - Postmus, Iris
AU - Verweij, Niek
AU - Van Enckevort, David J.
AU - Huffman, Jennifer E.
AU - White, Charles C.
AU - Feitosa, Mary F.
AU - Bartz, Traci M.
AU - Manichaikul, Ani
AU - Joshi, Peter K.
AU - Peloso, Gina M.
AU - Deelen, Patrick
AU - Van Dijk, Freerk
AU - Willemsen, Gonneke
AU - De Geus, Eco J.
AU - Milaneschi, Yuri
AU - Penninx, Brenda W.J.H.
AU - Francioli, Laurent C.
AU - Menelaou, Androniki
AU - Pulit, Sara L.
AU - Rivadeneira, Fernando
AU - Hofman, Albert
AU - Oostra, Ben A.
AU - Franco, Oscar H.
AU - Leach, Irene Mateo
AU - Beekman, Marian
AU - De Craen, Anton J.M.
AU - Uh, Hae Won
AU - Trochet, Holly
AU - Hocking, Lynne J.
AU - Porteous, David J.
AU - Sattar, Naveed
AU - Packard, Chris J.
AU - Buckley, Brendan M.
AU - Brody, Jennifer A.
AU - Bis, Joshua C.
AU - Rotter, Jerome I.
AU - Mychaleckyj, Josyf C.
AU - Campbell, Harry
AU - Duan, Qing
AU - Lange, Leslie A.
AU - Wilson, James F.
AU - Hottenga, Jouke Jan
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/3/9
Y1 - 2015/3/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84924363528
U2 - 10.1038/ncomms7065
DO - 10.1038/ncomms7065
M3 - Article
C2 - 25751400
AN - SCOPUS:84924363528
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 6065
ER -