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

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Surakka, Ida (author)

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

Article/chapterEnglish2015

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2015-05-11
Springer Science and Business Media LLC,2015

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LIBRIS-ID:oai:lup.lub.lu.se:bbe11594-fa68-4b81-ac3f-fd83165eb4ec
https://lup.lub.lu.se/record/5453441URI
https://doi.org/10.1038/ng.3300DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-256828URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:131352777URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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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Horikoshi, Momoko (author)
Mägi, Reedik (author)
Sarin, Antti-Pekka (author)
Mahajan, Anubha (author)
Lagou, Vasiliki (author)
Marullo, Letizia (author)
Ferreira, Teresa (author)
Miraglio, Benjamin (author)
Timonen, Sanna (author)
Kettunen, Johannes (author)
Pirinen, Matti (author)
Karjalainen, Juha (author)
Thorleifsson, Gudmar (author)
Hägg, SaraKarolinska Institutet,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)sarha464 (author)
Hottenga, Jouke-Jan (author)
Isaacs, Aaron (author)
Ladenvall, ClaesLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)med-cll (author)
Beekman, Marian (author)
Esko, Tõnu (author)
Ried, Janina S (author)
Nelson, Christopher P (author)
Willenborg, Christina (author)
Gustafsson, StefanUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)stegu732 (author)
Westra, Harm-Jan (author)
Blades, Matthew (author)
de Craen, Anton J M (author)
de Geus, Eco J (author)
Deelen, Joris (author)
Grallert, Harald (author)
Hamsten, AndersKarolinska Institutet (author)
Havulinna, Aki S (author)
Hengstenberg, Christian (author)
Houwing-Duistermaat, Jeanine J (author)
Hyppönen, Elina (author)
Karssen, Lennart C (author)
Lehtimäki, Terho (author)
Lyssenko, ValeriyaLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-vly (author)
Magnusson, Patrik K EKarolinska Institutet (author)
Mihailov, Evelin (author)
Müller-Nurasyid, Martina (author)
Mpindi, John-Patrick (author)
Lind, LarsKarolinska Institutet,Uppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (author)
Penninx, Brenda W J H (author)
Perola, Markus (author)
Pers, Tune H (author)
Peters, Annette (author)
Rung, Johan (author)
Smit, Johannes H (author)
Steinthorsdottir, Valgerdur (author)
Tobin, Martin D (author)
Tsernikova, Natalia (author)
van Leeuwen, Elisabeth M (author)
Viikari, Jorma S (author)
Willems, Sara M (author)
Willemsen, Gonneke (author)
Schunkert, Heribert (author)
Erdmann, Jeanette (author)
Samani, Nilesh J (author)
Kaprio, Jaakko (author)
Lind, Lars (author)
Gieger, Christian (author)
Metspalu, Andres (author)
Slagboom, P Eline (author)
Groop, LeifLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-lgr (author)
van Duijn, Cornelia M (author)
Eriksson, Johan G (author)
Jula, Antti (author)
Salomaa, Veikko (author)
Boomsma, Dorret I (author)
Power, Christine (author)
Raitakari, Olli T (author)
Ingelsson, ErikUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)ering425 (author)
Järvelin, Marjo-Riitta (author)
Thorsteinsdottir, Unnur (author)
Franke, Lude (author)
Ikonen, Elina (author)
Kallioniemi, Olli (author)
Pietiäinen, Vilja (author)
Lindgren, Cecilia M (author)
Stefansson, Kari (author)
Palotie, Aarno (author)
McCarthy, Mark I (author)
Morris, Andrew P (author)
Prokopenko, Inga (author)
Ripatti, Samuli (author)
Karjalainen, Julia (author)
Uppsala universitetMolekylär epidemiologi (creator_code:org_t)

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In:Nature Genetics: Springer Science and Business Media LLC47:6, s. 589-5971546-17181061-4036

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By the author/editor: Surakka, Ida; Horikoshi, Momok ...; Mägi, Reedik; Sarin, Antti-Pek ...; Mahajan, Anubha; Lagou, Vasiliki; show more...; Marullo, Letizia; Ferreira, Teresa; Miraglio, Benjam ...; Timonen, Sanna; Kettunen, Johann ...; Pirinen, Matti; Karjalainen, Juh ...; Thorleifsson, Gu ...; Hägg, Sara; Hottenga, Jouke- ...; Isaacs, Aaron; Ladenvall, Claes; Beekman, Marian; Esko, Tõnu; Ried, Janina S; Nelson, Christop ...; Willenborg, Chri ...; Gustafsson, Stef ...; Westra, Harm-Jan; Blades, Matthew; de Craen, Anton ...; de Geus, Eco J; Deelen, Joris; Grallert, Harald; Hamsten, Anders; Havulinna, Aki S; Hengstenberg, Ch ...; Houwing-Duisterm ...; Hyppönen, Elina; Karssen, Lennart ...; Lehtimäki, Terho; Lyssenko, Valeri ...; Magnusson, Patri ...; Mihailov, Evelin; Müller-Nurasyid, ...; Mpindi, John-Pat ...; Lind, Lars; Penninx, Brenda ...; Perola, Markus; Pers, Tune H; Peters, Annette; Rung, Johan; Smit, Johannes H; Steinthorsdottir ...; Tobin, Martin D; Tsernikova, Nata ...; van Leeuwen, Eli ...; Viikari, Jorma S; Willems, Sara M; Willemsen, Gonne ...; Schunkert, Herib ...; Erdmann, Jeanett ...; Samani, Nilesh J; Kaprio, Jaakko; Gieger, Christia ...; Metspalu, Andres; Slagboom, P Elin ...; Groop, Leif; van Duijn, Corne ...; Eriksson, Johan ...; Jula, Antti; Salomaa, Veikko; Boomsma, Dorret ...; Power, Christine; Raitakari, Olli ...; Ingelsson, Erik; Järvelin, Marjo- ...; Thorsteinsdottir ...; Franke, Lude; Ikonen, Elina; Kallioniemi, Oll ...; Pietiäinen, Vilj ...; Lindgren, Cecili ...; Stefansson, Kari; Palotie, Aarno; McCarthy, Mark I; Morris, Andrew P; Prokopenko, Inga; Ripatti, Samuli; Karjalainen, Jul ...; show less...

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