Biological, clinical and population relevance of 95 loci for blood lipids

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Teslovich, Tanya M. (author)

Biological, clinical and population relevance of 95 loci for blood lipids

Article/chapterEnglish2010

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Springer Science and Business Media LLC,2010
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LIBRIS-ID:oai:DiVA.org:uu-147275
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-147275URI
https://doi.org/10.1038/nature09270DOI
https://lup.lub.lu.se/record/1677988URI
http://kipublications.ki.se/Default.aspx?queryparsed=id:121097165URI

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Language:English
Summary in:English

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Notes

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
MEDICINE
MEDICIN

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Musunuru, Kiran (author)
Smith, Albert V. (author)
Edmondson, Andrew C. (author)
Stylianou, Ioannis M. (author)
Koseki, Masahiro (author)
Pirruccello, James P. (author)
Ripatti, Samuli (author)
Chasman, Daniel I. (author)
Willer, Cristen J. (author)
Johansen, Christopher T. (author)
Fouchier, Sigrid W. (author)
Isaacs, Aaron (author)
Peloso, Gina M. (author)
Barbalic, Maja (author)
Ricketts, Sally L. (author)
Bis, Joshua C. (author)
Aulchenko, Yurii S. (author)
Thorleifsson, Gudmar (author)
Feitosa, Mary F. (author)
Chambers, John (author)
Orho-Melander, MarjuLund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups(Swepub:lu)endo-mor (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
Johnson, Toby (author)
Li, Xiaohui (author)
Guo, Xiuqing (author)
Li, Mingyao (author)
Cho, Yoon Shin (author)
Go, Min Jin (author)
Kim, Young Jin (author)
Lee, Jong-Young (author)
Park, Taesung (author)
Kim, KyungaKarolinska Institutet (author)
Sim, Xueling (author)
Ong, Rick Twee-Hee (author)
Croteau-Chonka, Damien C. (author)
Lange, Leslie A. (author)
Smith, Joshua D. (author)
Song, Kijoung (author)
Zhao, Jing Hua (author)
Yuan, Xin (author)
Luan, Jian'an (author)
Lamina, Claudia (author)
Ziegler, Andreas (author)
Zhang, Weihua (author)
Zee, Robert Y. L. (author)
Wright, Alan F. (author)
Witteman, Jacqueline C. M. (author)
Wilson, James F. (author)
Willemsen, Gonneke (author)
Wichmann, H. -Erich (author)
Whitfield, John B. (author)
Waterworth, Dawn M. (author)
Wareham, Nicholas J. (author)
Waeber, Gerard (author)
Vollenweider, Peter (author)
Voight, Benjamin F. (author)
Vitart, Veronique (author)
Uitterlinden, Andre G. (author)
Uda, Manuela (author)
Tuomilehto, Jaakko (author)
Thompson, John R. (author)
Tanaka, Toshiko (author)
Surakka, Ida (author)
Stringham, Heather M. (author)
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Sinisalo, Juha (author)
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Scuteri, Angelo (author)
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Schlessinger, David (author)
Sanna, Serena (author)
Salomaa, Veikko (author)
Saharinen, Juha (author)
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Ruokonen, Aimo (author)
Rudan, Igor (author)
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Rieder, Mark (author)
Psaty, Bruce M. (author)
Pramstaller, Peter P. (author)
Pichler, Irene (author)
Perola, Markus (author)
Penninx, Brenda W. J. H. (author)
Pedersen, Nancy L.Karolinska Institutet (author)
Pattaro, Cristian (author)
Parker, Alex N. (author)
Pare, Guillaume (author)
Oostra, Ben A. (author)
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Johansson, ÅsaUppsala universitet,Institutionen för genetik och patologi(Swepub:uu)asjoh108 (author)
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Janssens, A. Cecile J. W. (author)
Ingelsson, ErikKarolinska Institutet (author)
Igi, WilmarUppsala universitet,Institutionen för genetik och patologi (author)
Hovingh, G. Kees (author)
Hottenga, Jouke-Jan (author)
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Havulinna, Aki S. (author)
Hastie, Nicholas D. (author)
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Gyllensten, UlfUppsala universitet,Institutionen för genetik och patologi(Swepub:uu)ulfgyll (author)
Guiducci, Candace (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)
Gonzalez, Elena (author)
Gieger, Christian (author)
Freimer, Nelson B. (author)
Ferrucci, Luigi (author)
Erdmann, Jeanette (author)
Elliott, Paul (author)
Ejebe, Kenechi G. (author)
Doering, Angela (author)
Dominiczak, Anna F. (author)
Demissie, Serkalem (author)
Deloukas, Panagiotis (author)
de Geus, Eco J. C. (author)
de Faire, UlfKarolinska Institutet (author)
Crawford, Gabriel (author)
Collins, Francis S. (author)
Chen, Yii-der I. (author)
Caulfield, Mark J. (author)
Campbell, Harry (author)
Burtt, Noel P. (author)
Bonnycastle, Lori L. (author)
Boomsma, Dorret I. (author)
Boekholdt, S. Matthijs (author)
Bergman, Richard N. (author)
Barroso, Ines (author)
Bandinelli, Stefania (author)
Ballantyne, Christie M. (author)
Assimes, Themistocles L. (author)
Quertermous, Thomas (author)
Altshuler, David (author)
Seielstad, Mark (author)
Wong, Tien Y. (author)
Tai, E-Shyong (author)
Feranil, Alan B. (author)
Kuzawa, Christopher W. (author)
Adair, Linda S. (author)
Taylor, Herman A., Jr. (author)
Borecki, Ingrid B. (author)
Gabriel, Stacey B. (author)
Wilson, James G. (author)
Holm, Hilma (author)
Thorsteinsdottir, Unnur (author)
Gudnason, Vilmundur (author)
Krauss, Ronald M. (author)
Mohlke, Karen L. (author)
Ordovas, Jose M. (author)
Munroe, Patricia B. (author)
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Tall, Alan R. (author)
Hegele, Robert A. (author)
Kastelein, John J. P. (author)
Schadt, Eric E. (author)
Rotter, Jerome I. (author)
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Strachan, David P. (author)
Mooser, Vincent (author)
Stefansson, Kari (author)
Reilly, Muredach P. (author)
Samani, Nilesh J. (author)
Schunkert, Heribert (author)
Cupples, L. Adrienne (author)
Sandhu, Manjinder S. (author)
Ridker, Paul M. (author)
Rader, Daniel J. (author)
van Duijn, Cornelia M. (author)
Peltonen, Leena (author)
Abecasis, Goncalo R. (author)
Boehnke, Michael (author)
Kathiresan, Sekar (author)
Genomik, diabetes och endokrinologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Nature: Springer Science and Business Media LLC466:7307, s. 707-7130028-08361476-4687

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By the author/editor: Teslovich, Tanya ...; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andre ...; Stylianou, Ioann ...; Koseki, Masahiro; show more...; Pirruccello, Jam ...; Ripatti, Samuli; Chasman, Daniel ...; Willer, Cristen ...; Johansen, Christ ...; Fouchier, Sigrid ...; Isaacs, Aaron; Peloso, Gina M.; Barbalic, Maja; Ricketts, Sally ...; Bis, Joshua C.; Aulchenko, Yurii ...; Thorleifsson, Gu ...; Feitosa, Mary F.; Chambers, John; Orho-Melander, M ...; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-H ...; Croteau-Chonka, ...; Lange, Leslie A.; Smith, Joshua D.; Song, Kijoung; Zhao, Jing Hua; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y. L ...; Wright, Alan F.; Witteman, Jacque ...; Wilson, James F.; Willemsen, Gonne ...; Wichmann, H. -Er ...; Whitfield, John ...; Waterworth, Dawn ...; Wareham, Nichola ...; Waeber, Gerard; Vollenweider, Pe ...; Voight, Benjamin ...; Vitart, Veroniqu ...; Uitterlinden, An ...; Uda, Manuela; Tuomilehto, Jaak ...; Thompson, John R ...; Tanaka, Toshiko; Surakka, Ida; Stringham, Heath ...; Spector, Tim D.; Soranzo, Nicole; Smit, Johannes H ...; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric ...; Scuteri, Angelo; Scott, James; Schlessinger, Da ...; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M.; Roberts, Robert; Rieder, Mark; Psaty, Bruce M.; Pramstaller, Pet ...; Pichler, Irene; Perola, Markus; Penninx, Brenda ...; Pedersen, Nancy ...; Pattaro, Cristia ...; Parker, Alex N.; Pare, Guillaume; Oostra, Ben A.; O'Donnell, Chris ...; Nieminen, Markku ...; Nickerson, Debor ...; Montgomery, Gran ...; Meitinger, Thoma ...; McPherson, Ruth; McCarthy, Mark I ...; McArdle, Wendy; Masson, David; Martin, Nicholas ...; Marroni, Fabio; Mangino, Massimo; Magnusson, Patri ...; Lucas, Gavin; Luben, Robert; Loos, Ruth J. F.; Lokki, Marja-Lii ...; Lettre, Guillaum ...; Langenberg, Clau ...; Launer, Lenore J ...; Lakatta, Edward ...; Laaksonen, Reijo; Kyvik, Kirsten O ...; Kronenberg, Flor ...; Koenig, Inke R.; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M.; Johansson, Åsa; Jarvelin, Marjo- ...; Janssens, A. Cec ...; Ingelsson, Erik; Igi, Wilmar; Hovingh, G. Kees; Hottenga, Jouke- ...; Hofman, Albert; Hicks, Andrew A.; Hengstenberg, Ch ...; Heid, Iris M.; Hayward, Carolin ...; Havulinna, Aki S ...; Hastie, Nicholas ...; Harris, Tamara B ...; Haritunians, Tal ...; Hall, Alistair S ...; Gyllensten, Ulf; Guiducci, Candac ...; Groop, Leif; Gonzalez, Elena; Gieger, Christia ...; Freimer, Nelson ...; Ferrucci, Luigi; Erdmann, Jeanett ...; Elliott, Paul; Ejebe, Kenechi G ...; Doering, Angela; Dominiczak, Anna ...; Demissie, Serkal ...; Deloukas, Panagi ...; de Geus, Eco J. ...; de Faire, Ulf; Crawford, Gabrie ...; Collins, Francis ...; Chen, Yii-der I.; Caulfield, Mark ...; Campbell, Harry; Burtt, Noel P.; Bonnycastle, Lor ...; Boomsma, Dorret ...; Boekholdt, S. Ma ...; Bergman, Richard ...; Barroso, Ines; Bandinelli, Stef ...; Ballantyne, Chri ...; Assimes, Themist ...; Quertermous, Tho ...; Altshuler, David; Seielstad, Mark; Wong, Tien Y.; Tai, E-Shyong; Feranil, Alan B.; Kuzawa, Christop ...; Adair, Linda S.; Taylor, Herman A ...; Borecki, Ingrid ...; Gabriel, Stacey ...; Wilson, James G.; Holm, Hilma; Thorsteinsdottir ...; Gudnason, Vilmun ...; Krauss, Ronald M ...; Mohlke, Karen L.; Ordovas, Jose M.; Munroe, Patricia ...; Kooner, Jaspal S ...; Tall, Alan R.; Hegele, Robert A ...; Kastelein, John ...; Schadt, Eric E.; Rotter, Jerome I ...; Boerwinkle, Eric; Strachan, David ...; Mooser, Vincent; Stefansson, Kari; Reilly, Muredach ...; Samani, Nilesh J ...; Schunkert, Herib ...; Cupples, L. Adri ...; Sandhu, Manjinde ...; Ridker, Paul M.; Rader, Daniel J.; van Duijn, Corne ...; Peltonen, Leena; Abecasis, Goncal ...; Boehnke, Michael; Kathiresan, Seka ...; show less...

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