The impact of low-frequency and rare variants on lipid levels

Surakka, I.; Horikoshi, M.; Magi, R.; Sarin, A. P.; Mahajan, A.; Lagou, V.; Marullo, L.; Ferreira, T.; Miraglio, B.; Timonen, S.; Kettunen, J.; Pirinen, M.; Karjalainen, J.; Thorleifsson, G.; Hagg, S.; Hottenga, J. J.; Isaacs, A.; Ladenvall, C.; Beekman, M.; Esko, T.; Ried, J. S.; Nelson, C. P.; Willenborg, C.; Gustafsson, S.; Westra, H. J.; Blades, M.; de Craen, A. J.; de Geus, E. J.; Deelen, J.; Grallert, H.; Hamsten, A.; Havulinna, A. S.; Hengstenberg, C.; Houwing-Duistermaat, J. J.; Hypponen, E.; Karssen, L. C.; Lehtimaki, T.; Lyssenko, V.; Magnusson, P. K.; Mihailov, E.; Muller-Nurasyid, M.; Mpindi, J. P.; Pedersen, N. L.; Penninx, B. W.; Perola, M.; Pers, T. H.; Peters, A.; Rung, J.; Smit, J. H.; Steinthorsdottir, V.; Tobin, M. D.; Tsernikova, N.; van Leeuwen, E. M.; Viikari, J. S.; Willems, S. M.; Willemsen, G.; Schunkert, H.; Erdmann, J.; Samani, N. J.; Kaprio, J.; Lind, L.; Gieger, C.; Metspalu, A.; Slagboom, P. E.; Groop, L.; van Duijn, C. M.; Eriksson, J. G.; Jula, A.; Salomaa, V.; Boomsma, D. I.; Power, C.; Raitakari, O. T.; Ingelsson, E.; Jarvelin, M. R.; Thorsteinsdottir, U.; Franke, L.; Ikonen, E.; Kallioniemi, O.; Pietiainen, V.; Lindgren, C. M.; Stefansson, K.; Palotie, A.; McCarthy, M. I.; Morris, A. P.; Prokopenko, I.; Ripatti, S.; Consortium, Engage

doi:10.1038/ng.3300

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The impact of low-frequency and rare variants on lipid levels

Surakka, I., Horikoshi, M., Magi, R., Sarin, A. P., Mahajan, A., Lagou, V., et al. (2015). The impact of low-frequency and rare variants on lipid levels. Nat Genet, 47(6), 589-97. doi:10.1038/ng.3300.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000B-6E7B-1 Version Permalink: https://hdl.handle.net/21.11116/0000-000C-087E-F

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https://www.ncbi.nlm.nih.gov/pubmed/25961943 (Any fulltext) Open Access status unknown

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Surakka, I., Author
Horikoshi, M., Author
Magi, R., Author
Sarin, A. P., Author
Mahajan, A., Author
Lagou, V., Author
Marullo, L., Author
Ferreira, T., Author
Miraglio, B., Author
Timonen, S., Author
Kettunen, J., Author
Pirinen, M., Author
Karjalainen, J., Author
Thorleifsson, G., Author
Hagg, S., Author
Hottenga, J. J., Author
Isaacs, A., Author
Ladenvall, C., Author
Beekman, M., Author
Esko, T., Author
Ried, J. S., AuthorNelson, C. P., AuthorWillenborg, C., AuthorGustafsson, S., AuthorWestra, H. J., AuthorBlades, M., Authorde Craen, A. J., Authorde Geus, E. J., AuthorDeelen, J.¹, Author Grallert, H., AuthorHamsten, A., AuthorHavulinna, A. S., AuthorHengstenberg, C., AuthorHouwing-Duistermaat, J. J., AuthorHypponen, E., AuthorKarssen, L. C., AuthorLehtimaki, T., AuthorLyssenko, V., AuthorMagnusson, P. K., AuthorMihailov, E., AuthorMuller-Nurasyid, M., AuthorMpindi, J. P., AuthorPedersen, N. L., AuthorPenninx, B. W., AuthorPerola, M., AuthorPers, T. H., AuthorPeters, A., AuthorRung, J., AuthorSmit, J. H., AuthorSteinthorsdottir, V., AuthorTobin, M. D., AuthorTsernikova, N., Authorvan Leeuwen, E. M., AuthorViikari, J. S., AuthorWillems, S. M., AuthorWillemsen, G., AuthorSchunkert, H., AuthorErdmann, J., AuthorSamani, N. J., AuthorKaprio, J., AuthorLind, L., AuthorGieger, C., AuthorMetspalu, A., AuthorSlagboom, P. E., Author Groop, L., Authorvan Duijn, C. M., AuthorEriksson, J. G., AuthorJula, A., AuthorSalomaa, V., AuthorBoomsma, D. I., AuthorPower, C., AuthorRaitakari, O. T., AuthorIngelsson, E., AuthorJarvelin, M. R., AuthorThorsteinsdottir, U., AuthorFranke, L., AuthorIkonen, E., AuthorKallioniemi, O., AuthorPietiainen, V., AuthorLindgren, C. M., AuthorStefansson, K., AuthorPalotie, A., AuthorMcCarthy, M. I., AuthorMorris, A. P., AuthorProkopenko, I., AuthorRipatti, S., AuthorConsortium, Engage, Author more..

Affiliations:
1Deelen – Genetics and Biomarkers of Human Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394006

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Free keywords: Dyslipidemias/genetics Gene Frequency Genetic Loci Genome-Wide Association Study Humans Linkage Disequilibrium Lipid Metabolism/*genetics Mutation, Missense Polymorphism, Single Nucleotide Sequence Analysis, DNA

Abstract: Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.

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Dates: Published Online: 2016-06Date issued: 2015-05-12

Publication Status: Issued

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Identifiers: Other: 25961943
DOI: 10.1038/ng.3300
ISSN: 1546-1718 (Electronic)1061-4036 (Linking)

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Title: Nat Genet

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Pages: - Volume / Issue: 47 (6) Sequence Number: - Start / End Page: 589 - 97 Identifier: -