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)
|
Text
105793.pdf - Published Version Available under License Creative Commons Attribution. 387kB |
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 > School of Cardiovascular & Metabolic Health |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric