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

van Leeuwen, E. M. et al. (2015) Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels. Nature Communications, 6, 6065. (doi:10.1038/ncomms7065) (PMID:25751400) (PMCID:PMC4366498)

van Leeuwen, E. M. et al. (2015) Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels. Nature Communications, 6, 6065. (doi:10.1038/ncomms7065) (PMID:25751400) (PMCID:PMC4366498)

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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 (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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott J, Professor David and Packard, Professor Chris and Sattar, Professor Naveed
Authors: van Leeuwen, E. M., Karssen, L. C., Deelen, J., Isaacs, A., Medina-Gomez, C., Mbarek, H., Kanterakis, A., Trompet, S., Postmus, I., Verweij, N., van Enckevort, D. J., Huffman, J. E., White, C. C., Feitosa, M. F., Bartz, T. M., Manichaikul, A., Joshi, P. K., Peloso, G. M., Deelen, P., van Dijk, F., Willemsen, G., de Geus, E. J., Milaneschi, Y., Penninx, B. W.J.H., Francioli, L. C., Menelaou, A., Pulit, S. L., Rivadeneira, F., Hofman, A., Oostra, B. A., Franco, O. H., Leach, I. M., Beekman, M., de Craen, A. J.M., Uh, H.-W., Trochet, H., Hocking, L. J., Porteous, D. J., Sattar, N., Packard, C., Buckley, B. M., Brody, J. A., Bis, J. C., Rotter, J. I., Mychaleckyj, J. C., Campbell, H., Duan, Q., Lange, L. A., Wilson, J. F., Hayward, C., Polasek, O., Vitart, V., Rudan, I., Wright, A. F., Rich, S. S., Psaty, B. M., Borecki, I. B., Kearney, P. M., Stott, D. J., Adrienne Cupples, L., Neerincx, P. B.T., Elbers, C. C., Francesco Palamara, P., Pe’er, I., Abdellaoui, A., Kloosterman, W. P., van Oven, M., Vermaat, M., Li, M., Laros, J. F.J., Stoneking, M., de Knijff, P., Kayser, M., Veldink, J. H., van den Berg, L. H., Byelas, H., den Dunnen, J. T., Dijkstra, M., Amin, N., Joeri van der Velde, K., van Setten, J., Kattenberg, M., van Schaik, B. D.C., Bot, J., Nijman, I. J., Mei, H., Koval, V., Ye, K., Lameijer, E.-W., Moed, M. H., Hehir-Kwa, J. Y., Handsaker, R. E., Sunyaev, S. R., Sohail, M., Hormozdiari, F., Marschall, T., Schönhuth, A., Guryev, V., Suchiman, H. E. D., Wolffenbuttel, B. H., Platteel, M., Pitts, S. J., Potluri, S., Cox, D. R., Li, Q., Li, Y., Du, Y., Chen, R., Cao, H., Li, N., Cao, S., Wang, J., Bovenberg, J. A., Jukema, J. W., van der Harst, P., Sijbrands, E. J., Hottenga, J.-J., Uitterlinden, A. G., Swertz, M. A., van Ommen, G.-J. B., de Bakker, P. I.W., Eline Slagboom, P., Boomsma, D. I., Wijmenga, C., and van Duijn, C. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2015 Macmillan Publishers Limited
First Published:First published in Nature Communications 6:6065
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
381721Generation ScotlandAnna DominiczakScottish Executive Health Department (SEHHD-CSO)CZD/16/6RI CARDIOVASCULAR & MEDICAL SCIENCES
381724Generation ScotlandAnna DominiczakScottish Executive Health Department (SEHHD-CSO)CZD/16/6RI CARDIOVASCULAR & MEDICAL SCIENCES