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

T.M. Teslovich; K. Musunuru; A.V. Smith; A.C. Edmondson; I.M. Stylianou; G. Willemsen; A.G. Uitterlinden; B.W.J.H. Penninx; GW Montgomery; N.G. Martin; J.J. Hottenga; E.J.C. de Geus; D.I. Boomsma; C.M. van Duijn; L. Peltonen; G.R. Abecasis; M. Boehnke; S. Kathiresan; Masahiro Koseki; James P. Pirruccello; Samuli Ripatti; Daniel I. Chasman; Cristen J. Willer; Christopher T. Johansen; Sigrid W. Fouchier; Aaron Isaacs; Gina M. Peloso; Maja Barbalic; Sally L. Ricketts; Joshua C. Bis; Yurii S. Aulchenko; Gudmar Thorleifsson; Mary F. Feitosa; John Chambers; Marju Orho-Melander; Olle Melander; Toby Johnson; Xiaohui Li; Xiuqing Guo; Mingyao Li; Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jong-Young Lee; Taesung Park; Kyunga Kim; Xueling Sim; Rick Twee-Hee Ong; Damien C. Croteau-Chonka; Leslie A. Lange; Joshua D. Smith; Kijoung Song; Jing Hua Zhao; Xin Yuan; Jian'an Luan; Claudia Lamina; Andreas Ziegler; Weihua Zhang; Robert Y. L. Zee; Alan F. Wright; Jacqueline C. M. Witteman; James F. Wilson; H.-Erich Wichmann; John B. Whitfield; Dawn M. Waterworth; Nicholas J. Wareham; Gérard Waeber; Peter Vollenweider; Benjamin F. Voight; Veronique Vitart; Manuela Uda; Jaakko Tuomilehto; John R. Thompson; Toshiko Tanaka; Ida Surakka; Heather M. Stringham; Tim D. Spector; Nicole Soranzo; Johannes H. Smit; Juha Sinisalo; Kaisa Silander; Eric J. G. Sijbrands; Angelo Scuteri; James Scott; David Schlessinger; Serena Sanna; Veikko Salomaa; Juha Saharinen; Chiara Sabatti; Aimo Ruokonen; Igor Rudan; Lynda M. Rose; Robert Roberts; Mark Rieder; Bruce M. Psaty; Peter P. Pramstaller; Irene Pichler; Markus Perola; Nancy L. Pedersen; Cristian Pattaro; Alex N. Parker; Guillaume Pare; Ben A. Oostra; Christopher J. O'Donnell; Markku S. Nieminen; Deborah A. Nickerson; Grant W. Montgomery; Thomas Meitinger; Ruth McPherson; Mark I. McCarthy; Wendy McArdle; David Masson; Fabio Marroni; Massimo Mangino; Patrik K. E. Magnusson; Gavin Lucas; Robert Luben; Ruth J. F. Loos; Marja-Liisa Lokki; Guillaume Lettre; Claudia Langenberg; Lenore J. Launer; Edward G. Lakatta; Reijo Laaksonen; Kirsten O. Kyvik; Florian Kronenberg; Inke R. König; Kay-Tee Khaw; Jaakko Kaprio; Lee M. Kaplan; Asa Johansson; Marjo-Riitta Jarvelin; A. Cecile J. W. Janssens; Erik Ingelsson; Wilmar Igl; G. Kees Hovingh; Albert Hofman; Andrew A. Hicks; Christian Hengstenberg; Iris M. Heid; Caroline Hayward; Aki S. Havulinna; Nicholas D. Hastie; Tamara B. Harris; Talin Haritunians; Alistair S. Hall; Ulf Gyllensten; Candace Guiducci; Leif C. Groop; Elena Gonzalez; Christian Gieger; Nelson B. Freimer; Luigi Ferrucci; Jeanette Erdmann; Paul Elliott; Kenechi G. Ejebe; Angela Döring; Anna F. Dominiczak; Serkalem Demissie; Panagiotis Deloukas; Ulf de Faire; Gabriel Crawford; Francis S. Collins; Yii-der I. Chen; Mark J. Caulfield; Harry Campbell; Noel P. Burtt; Lori L. Bonnycastle; S. Matthijs Boekholdt; Richard N. Bergman; Inês Barroso; Stefania Bandinelli; Christie M. Ballantyne; Themistocles L. Assimes; Thomas Quertermous; David Altshuler; Mark Seielstad; Tien Y. Wong; E.-Shyong Tai; Alan B. Feranil; Christopher W. Kuzawa; Linda S. Adair; Herman A. Taylor; Ingrid B. Borecki; Stacey B. Gabriel; James G. Wilson; Hilma Holm; Unnur Thorsteinsdottir; Vilmundur Gudnason; Ronald M. Krauss; Karen L. Mohlke; Jose M. Ordovas; Patricia B. Munroe; Jaspal S. Kooner; Alan R. Tall; Robert A. Hegele; John J. P. Kastelein; Eric E. Schadt; Jerome I. Rotter; Eric Boerwinkle; David P. Strachan; Vincent Mooser; Kari Stefansson; Muredach P. Reilly; Nilesh J. Samani; Heribert Schunkert; L. Adrienne Cupples; Manjinder S. Sandhu; Paul M. Ridker; Daniel J. Rader

doi:https://doi.org/10.1038/nature09270

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

T.M. Teslovich, K. Musunuru, A.V. Smith, A.C. Edmondson, I.M. Stylianou, G. Willemsen, A.G. Uitterlinden, B.W.J.H. Penninx, GW Montgomery, N.G. Martin, J.J. Hottenga, E.J.C. de Geus, D.I. Boomsma, C.M. van Duijn, L. Peltonen, G.R. Abecasis, M. Boehnke, S. Kathiresan, Masahiro Koseki, James P. PirruccelloSamuli Ripatti, Daniel I. Chasman, Cristen J. Willer, Christopher T. Johansen, Sigrid W. Fouchier, Aaron Isaacs, Gina M. Peloso, Maja Barbalic, Sally L. Ricketts, Joshua C. Bis, Yurii S. Aulchenko, Gudmar Thorleifsson, Mary F. Feitosa, John Chambers, Marju Orho-Melander, Olle Melander, Toby Johnson, Xiaohui Li, Xiuqing Guo, Mingyao Li, Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jong-Young Lee, Taesung Park, Kyunga Kim, Xueling Sim, Rick Twee-Hee Ong, Damien C. Croteau-Chonka, Leslie A. Lange, Joshua D. Smith, Kijoung Song, Jing Hua Zhao, Xin Yuan, Jian'an Luan, Claudia Lamina, Andreas Ziegler, Weihua Zhang, Robert Y. L. Zee, Alan F. Wright, Jacqueline C. M. Witteman, James F. Wilson, H.-Erich Wichmann, John B. Whitfield, Dawn M. Waterworth, Nicholas J. Wareham, Gérard Waeber, Peter Vollenweider, Benjamin F. Voight, Veronique Vitart, Manuela Uda, Jaakko Tuomilehto, John R. Thompson, Toshiko Tanaka, Ida Surakka, Heather M. Stringham, Tim D. Spector, Nicole Soranzo, Johannes H. Smit, Juha Sinisalo, Kaisa Silander, Eric J. G. Sijbrands, Angelo Scuteri, James Scott, David Schlessinger, Serena Sanna, Veikko Salomaa, Juha Saharinen, Chiara Sabatti, Aimo Ruokonen, Igor Rudan, Lynda M. Rose, Robert Roberts, Mark Rieder, Bruce M. Psaty, Peter P. Pramstaller, Irene Pichler, Markus Perola, Nancy L. Pedersen, Cristian Pattaro, Alex N. Parker, Guillaume Pare, Ben A. Oostra, Christopher J. O'Donnell, Markku S. Nieminen, Deborah A. Nickerson, Grant W. Montgomery, Thomas Meitinger, Ruth McPherson, Mark I. McCarthy, Wendy McArdle, David Masson, Fabio Marroni, Massimo Mangino, Patrik K. E. Magnusson, Gavin Lucas, Robert Luben, Ruth J. F. Loos, Marja-Liisa Lokki, Guillaume Lettre, Claudia Langenberg, Lenore J. Launer, Edward G. Lakatta, Reijo Laaksonen, Kirsten O. Kyvik, Florian Kronenberg, Inke R. König, Kay-Tee Khaw, Jaakko Kaprio, Lee M. Kaplan, Asa Johansson, Marjo-Riitta Jarvelin, A. Cecile J. W. Janssens, Erik Ingelsson, Wilmar Igl, G. Kees Hovingh, Albert Hofman, Andrew A. Hicks, Christian Hengstenberg, Iris M. Heid, Caroline Hayward, Aki S. Havulinna, Nicholas D. Hastie, Tamara B. Harris, Talin Haritunians, Alistair S. Hall, Ulf Gyllensten, Candace Guiducci, Leif C. Groop, Elena Gonzalez, Christian Gieger, Nelson B. Freimer, Luigi Ferrucci, Jeanette Erdmann, Paul Elliott, Kenechi G. Ejebe, Angela Döring, Anna F. Dominiczak, Serkalem Demissie, Panagiotis Deloukas, Ulf de Faire, Gabriel Crawford, Francis S. Collins, Yii-der I. Chen, Mark J. Caulfield, Harry Campbell, Noel P. Burtt, Lori L. Bonnycastle, S. Matthijs Boekholdt, Richard N. Bergman, Inês Barroso, Stefania Bandinelli, Christie M. Ballantyne, Themistocles L. Assimes, Thomas Quertermous, David Altshuler, Mark Seielstad, Tien Y. Wong, E.-Shyong Tai, Alan B. Feranil, Christopher W. Kuzawa, Linda S. Adair, Herman A. Taylor, Ingrid B. Borecki, Stacey B. Gabriel, James G. Wilson, Hilma Holm, Unnur Thorsteinsdottir, Vilmundur Gudnason, Ronald M. Krauss, Karen L. Mohlke, Jose M. Ordovas, Patricia B. Munroe, Jaspal S. Kooner, Alan R. Tall, Robert A. Hegele, John J. P. Kastelein, Eric E. Schadt, Jerome I. Rotter, Eric Boerwinkle, David P. Strachan, Vincent Mooser, Kari Stefansson, Muredach P. Reilly, Nilesh J. Samani, Heribert Schunkert, L. Adrienne Cupples, Manjinder S. Sandhu, Paul M. Ridker, Daniel J. Rader

Research output: Contribution to journal › Article › Academic › peer-review

2895 Citations (Scopus)

Abstract

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<-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. © 2010 Macmillan Publishers Limited. All rights reserved.

Original language	English
Pages (from-to)	707-713
Journal	NATURE
Volume	466
Issue number	7307
DOIs	https://doi.org/10.1038/nature09270
Publication status	Published - 2010

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https://doi.org/10.1038/nature09270

Cite this

Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Willemsen, G., Uitterlinden, A. G., Penninx, B. W. J. H., Montgomery, GW., Martin, N. G., Hottenga, J. J., de Geus, E. J. C., Boomsma, D. I., van Duijn, C. M., Peltonen, L., Abecasis, G. R., Boehnke, M., Kathiresan, S., Koseki, M., ... Rader, D. J. (2010). Biological, clinical and population relevance of 95 loci for blood lipids. NATURE, 466(7307), 707-713. https://doi.org/10.1038/nature09270

@article{55e30d151fce474ebe7774928126bdfe,

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

abstract = "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<-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. {\textcopyright} 2010 Macmillan Publishers Limited. All rights reserved.",

author = "T.M. Teslovich and K. Musunuru and A.V. Smith and A.C. Edmondson and I.M. Stylianou and G. Willemsen and A.G. Uitterlinden and B.W.J.H. Penninx and GW Montgomery and N.G. Martin and J.J. Hottenga and {de Geus}, E.J.C. and D.I. Boomsma and {van Duijn}, C.M. and L. Peltonen and G.R. Abecasis and M. Boehnke and S. Kathiresan and Masahiro Koseki and Pirruccello, {James P.} and Samuli Ripatti and Chasman, {Daniel I.} and Willer, {Cristen J.} and Johansen, {Christopher T.} and Fouchier, {Sigrid W.} and Aaron Isaacs and Peloso, {Gina M.} and Maja Barbalic and Ricketts, {Sally L.} and Bis, {Joshua C.} and Aulchenko, {Yurii S.} and Gudmar Thorleifsson and Feitosa, {Mary F.} and John Chambers and Marju Orho-Melander and Olle Melander and Toby Johnson and Xiaohui Li and Xiuqing Guo and Mingyao Li and {Shin Cho}, Yoon and {Jin Go}, Min and {Jin Kim}, Young and Jong-Young Lee and Taesung Park and Kyunga Kim and Xueling Sim and {Twee-Hee Ong}, Rick and Croteau-Chonka, {Damien C.} and Lange, {Leslie A.} and Smith, {Joshua D.} and Kijoung Song and {Hua Zhao}, Jing and Xin Yuan and Jian'an Luan and Claudia Lamina and Andreas Ziegler and Weihua Zhang and Zee, {Robert Y. L.} and Wright, {Alan F.} and Witteman, {Jacqueline C. M.} and Wilson, {James F.} and H.-Erich Wichmann and Whitfield, {John B.} and Waterworth, {Dawn M.} and Wareham, {Nicholas J.} and G{\'e}rard Waeber and Peter Vollenweider and Voight, {Benjamin F.} and Veronique Vitart and Manuela Uda and Jaakko Tuomilehto and Thompson, {John R.} and Toshiko Tanaka and Ida Surakka and Stringham, {Heather M.} and Spector, {Tim D.} and Nicole Soranzo and Smit, {Johannes H.} and Juha Sinisalo and Kaisa Silander and Sijbrands, {Eric J. G.} and Angelo Scuteri and James Scott and David Schlessinger and Serena Sanna and Veikko Salomaa and Juha Saharinen and Chiara Sabatti and Aimo Ruokonen and Igor Rudan and Rose, {Lynda M.} and Robert Roberts and Mark Rieder and Psaty, {Bruce M.} and Pramstaller, {Peter P.} and Irene Pichler and Markus Perola and Pedersen, {Nancy L.} and Cristian Pattaro and Parker, {Alex N.} and Guillaume Pare and Oostra, {Ben A.} and O'Donnell, {Christopher J.} and Nieminen, {Markku S.} and Nickerson, {Deborah A.} and Montgomery, {Grant W.} and Thomas Meitinger and Ruth McPherson and McCarthy, {Mark I.} and Wendy McArdle and David Masson and Fabio Marroni and Massimo Mangino and Magnusson, {Patrik K. E.} and Gavin Lucas and Robert Luben and Loos, {Ruth J. F.} and Marja-Liisa Lokki and Guillaume Lettre and Claudia Langenberg and Launer, {Lenore J.} and Lakatta, {Edward G.} and Reijo Laaksonen and Kyvik, {Kirsten O.} and Florian Kronenberg and K{\"o}nig, {Inke R.} and Kay-Tee Khaw and Jaakko Kaprio and Kaplan, {Lee M.} and Asa Johansson and Marjo-Riitta Jarvelin and Janssens, {A. Cecile J. W.} and Erik Ingelsson and Wilmar Igl and Hovingh, {G. Kees} and Albert Hofman and Hicks, {Andrew A.} and Christian Hengstenberg and Heid, {Iris M.} and Caroline Hayward and Havulinna, {Aki S.} and Hastie, {Nicholas D.} and Harris, {Tamara B.} and Talin Haritunians and Hall, {Alistair S.} and Ulf Gyllensten and Candace Guiducci and Groop, {Leif C.} and Elena Gonzalez and Christian Gieger and Freimer, {Nelson B.} and Luigi Ferrucci and Jeanette Erdmann and Paul Elliott and Ejebe, {Kenechi G.} and Angela D{\"o}ring and Dominiczak, {Anna F.} and Serkalem Demissie and Panagiotis Deloukas and {de Faire}, Ulf and Gabriel Crawford and Collins, {Francis S.} and Chen, {Yii-der I.} and Caulfield, {Mark J.} and Harry Campbell and Burtt, {Noel P.} and Bonnycastle, {Lori L.} and Boekholdt, {S. Matthijs} and Bergman, {Richard N.} and In{\^e}s Barroso and Stefania Bandinelli and Ballantyne, {Christie M.} and Assimes, {Themistocles L.} and Thomas Quertermous and David Altshuler and Mark Seielstad and Wong, {Tien Y.} and E.-Shyong Tai and Feranil, {Alan B.} and Kuzawa, {Christopher W.} and Adair, {Linda S.} and Taylor, {Herman A.} and Borecki, {Ingrid B.} and Gabriel, {Stacey B.} and Wilson, {James G.} and Hilma Holm and Unnur Thorsteinsdottir and Vilmundur Gudnason and Krauss, {Ronald M.} and Mohlke, {Karen L.} and Ordovas, {Jose M.} and Munroe, {Patricia B.} and Kooner, {Jaspal S.} and Tall, {Alan R.} and Hegele, {Robert A.} and Kastelein, {John J. P.} and Schadt, {Eric E.} and Rotter, {Jerome I.} and Eric Boerwinkle and Strachan, {David P.} and Vincent Mooser and Kari Stefansson and Reilly, {Muredach P.} and Samani, {Nilesh J.} and Heribert Schunkert and Cupples, {L. Adrienne} and Sandhu, {Manjinder S.} and Ridker, {Paul M.} and Rader, {Daniel J.}",

year = "2010",

doi = "https://doi.org/10.1038/nature09270",

language = "English",

volume = "466",

pages = "707--713",

journal = "NATURE",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7307",

}

Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Willemsen, G, Uitterlinden, AG, Penninx, BWJH, Montgomery, GW, Martin, NG, Hottenga, JJ, de Geus, EJC, Boomsma, DI, van Duijn, CM, Peltonen, L, Abecasis, GR, Boehnke, M, Kathiresan, S, Koseki, M, Pirruccello, JP, Ripatti, S, Chasman, DI, Willer, CJ, Johansen, CT, Fouchier, SW, Isaacs, A, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Aulchenko, YS, Thorleifsson, G, Feitosa, MF, Chambers, J, Orho-Melander, M, Melander, O, Johnson, T, Li, X, Guo, X, Li, M, Shin Cho, Y, Jin Go, M, Jin Kim, Y, Lee, J-Y, Park, T, Kim, K, Sim, X, Twee-Hee Ong, R, Croteau-Chonka, DC, Lange, LA, Smith, JD, Song, K, Hua Zhao, J, Yuan, X, Luan, J, Lamina, C, Ziegler, A, Zhang, W, Zee, RYL, Wright, AF, Witteman, JCM, Wilson, JF, Wichmann, H-E, Whitfield, JB, Waterworth, DM, Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uda, M, Tuomilehto, J, Thompson, JR, Tanaka, T, Surakka, I, Stringham, HM, Spector, TD, Soranzo, N, Smit, JH, Sinisalo, J, Silander, K, Sijbrands, EJG, Scuteri, A, Scott, J, Schlessinger, D, Sanna, S, Salomaa, V, Saharinen, J, Sabatti, C, Ruokonen, A, Rudan, I, Rose, LM, Roberts, R, Rieder, M, Psaty, BM, Pramstaller, PP, Pichler, I, Perola, M, Pedersen, NL, Pattaro, C, Parker, AN, Pare, G, Oostra, BA, O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, Meitinger, T, McPherson, R, McCarthy, MI, McArdle, W, Masson, D, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, M-L, Lettre, G, Langenberg, C, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, König, IR, Khaw, K-T, Kaprio, J, Kaplan, LM, Johansson, A, Jarvelin, M-R, Janssens, ACJW, Ingelsson, E, Igl, W, Hovingh, GK, Hofman, A, Hicks, AA, Hengstenberg, C, Heid, IM, Hayward, C, Havulinna, AS, Hastie, ND, Harris, TB, Haritunians, T, Hall, AS, Gyllensten, U, Guiducci, C, Groop, LC, Gonzalez, E, Gieger, C, Freimer, NB, Ferrucci, L, Erdmann, J, Elliott, P, Ejebe, KG, Döring, A, Dominiczak, AF, Demissie, S, Deloukas, P, de Faire, U, Crawford, G, Collins, FS, Chen, YI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boekholdt, SM, Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, CM, Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, E-S, Feranil, AB, Kuzawa, CW, Adair, LS, Taylor, HA, Borecki, IB, Gabriel, SB, Wilson, JG, Holm, H, Thorsteinsdottir, U, Gudnason, V, Krauss, RM, Mohlke, KL, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, JJP, Schadt, EE, Rotter, JI, Boerwinkle, E, Strachan, DP, Mooser, V, Stefansson, K, Reilly, MP, Samani, NJ, Schunkert, H, Cupples, LA, Sandhu, MS, Ridker, PM & Rader, DJ 2010, 'Biological, clinical and population relevance of 95 loci for blood lipids', NATURE, vol. 466, no. 7307, pp. 707-713. https://doi.org/10.1038/nature09270

TY - JOUR

T1 - Biological, clinical and population relevance of 95 loci for blood lipids

AU - Teslovich, T.M.

AU - Musunuru, K.

AU - Smith, A.V.

AU - Edmondson, A.C.

AU - Stylianou, I.M.

AU - Willemsen, G.

AU - Uitterlinden, A.G.

AU - Penninx, B.W.J.H.

AU - Montgomery, GW

AU - Martin, N.G.

AU - Hottenga, J.J.

AU - de Geus, E.J.C.

AU - Boomsma, D.I.

AU - van Duijn, C.M.

AU - Peltonen, L.

AU - Abecasis, G.R.

AU - Boehnke, M.

AU - Kathiresan, S.

AU - Koseki, Masahiro

AU - Pirruccello, James P.

AU - Ripatti, Samuli

AU - Chasman, Daniel I.

AU - Willer, Cristen J.

AU - Johansen, Christopher T.

AU - Fouchier, Sigrid W.

AU - Isaacs, Aaron

AU - Peloso, Gina M.

AU - Barbalic, Maja

AU - Ricketts, Sally L.

AU - Bis, Joshua C.

AU - Aulchenko, Yurii S.

AU - Thorleifsson, Gudmar

AU - Feitosa, Mary F.

AU - Chambers, John

AU - Orho-Melander, Marju

AU - Melander, Olle

AU - Johnson, Toby

AU - Li, Xiaohui

AU - Guo, Xiuqing

AU - Li, Mingyao

AU - Shin Cho, Yoon

AU - Jin Go, Min

AU - Jin Kim, Young

AU - Lee, Jong-Young

AU - Park, Taesung

AU - Kim, Kyunga

AU - Sim, Xueling

AU - Twee-Hee Ong, Rick

AU - Croteau-Chonka, Damien C.

AU - Lange, Leslie A.

AU - Smith, Joshua D.

AU - Song, Kijoung

AU - Hua Zhao, Jing

AU - Yuan, Xin

AU - Luan, Jian'an

AU - Lamina, Claudia

AU - Ziegler, Andreas

AU - Zhang, Weihua

AU - Zee, Robert Y. L.

AU - Wright, Alan F.

AU - Witteman, Jacqueline C. M.

AU - Wilson, James F.

AU - Wichmann, H.-Erich

AU - Whitfield, John B.

AU - Waterworth, Dawn M.

AU - Wareham, Nicholas J.

AU - Waeber, Gérard

AU - Vollenweider, Peter

AU - Voight, Benjamin F.

AU - Vitart, Veronique

AU - Uda, Manuela

AU - Tuomilehto, Jaakko

AU - Thompson, John R.

AU - Tanaka, Toshiko

AU - Surakka, Ida

AU - Stringham, Heather M.

AU - Spector, Tim D.

AU - Soranzo, Nicole

AU - Smit, Johannes H.

AU - Sinisalo, Juha

AU - Silander, Kaisa

AU - Sijbrands, Eric J. G.

AU - Scuteri, Angelo

AU - Scott, James

AU - Schlessinger, David

AU - Sanna, Serena

AU - Salomaa, Veikko

AU - Saharinen, Juha

AU - Sabatti, Chiara

AU - Ruokonen, Aimo

AU - Rudan, Igor

AU - Rose, Lynda M.

AU - Roberts, Robert

AU - Rieder, Mark

AU - Psaty, Bruce M.

AU - Pramstaller, Peter P.

AU - Pichler, Irene

AU - Perola, Markus

AU - Pedersen, Nancy L.

AU - Pattaro, Cristian

AU - Parker, Alex N.

AU - Pare, Guillaume

AU - Oostra, Ben A.

AU - O'Donnell, Christopher J.

AU - Nieminen, Markku S.

AU - Nickerson, Deborah A.

AU - Montgomery, Grant W.

AU - Meitinger, Thomas

AU - McPherson, Ruth

AU - McCarthy, Mark I.

AU - McArdle, Wendy

AU - Masson, David

AU - Marroni, Fabio

AU - Mangino, Massimo

AU - Magnusson, Patrik K. E.

AU - Lucas, Gavin

AU - Luben, Robert

AU - Loos, Ruth J. F.

AU - Lokki, Marja-Liisa

AU - Lettre, Guillaume

AU - Langenberg, Claudia

AU - Launer, Lenore J.

AU - Lakatta, Edward G.

AU - Laaksonen, Reijo

AU - Kyvik, Kirsten O.

AU - Kronenberg, Florian

AU - König, Inke R.

AU - Khaw, Kay-Tee

AU - Kaprio, Jaakko

AU - Kaplan, Lee M.

AU - Johansson, Asa

AU - Jarvelin, Marjo-Riitta

AU - Janssens, A. Cecile J. W.

AU - Ingelsson, Erik

AU - Igl, Wilmar

AU - Hovingh, G. Kees

AU - Hofman, Albert

AU - Hicks, Andrew A.

AU - Hengstenberg, Christian

AU - Heid, Iris M.

AU - Hayward, Caroline

AU - Havulinna, Aki S.

AU - Hastie, Nicholas D.

AU - Harris, Tamara B.

AU - Haritunians, Talin

AU - Hall, Alistair S.

AU - Gyllensten, Ulf

AU - Guiducci, Candace

AU - Groop, Leif C.

AU - Gonzalez, Elena

AU - Gieger, Christian

AU - Freimer, Nelson B.

AU - Ferrucci, Luigi

AU - Erdmann, Jeanette

AU - Elliott, Paul

AU - Ejebe, Kenechi G.

AU - Döring, Angela

AU - Dominiczak, Anna F.

AU - Demissie, Serkalem

AU - Deloukas, Panagiotis

AU - de Faire, Ulf

AU - Crawford, Gabriel

AU - Collins, Francis S.

AU - Chen, Yii-der I.

AU - Caulfield, Mark J.

AU - Campbell, Harry

AU - Burtt, Noel P.

AU - Bonnycastle, Lori L.

AU - Boekholdt, S. Matthijs

AU - Bergman, Richard N.

AU - Barroso, Inês

AU - Bandinelli, Stefania

AU - Ballantyne, Christie M.

AU - Assimes, Themistocles L.

AU - Quertermous, Thomas

AU - Altshuler, David

AU - Seielstad, Mark

AU - Wong, Tien Y.

AU - Tai, E.-Shyong

AU - Feranil, Alan B.

AU - Kuzawa, Christopher W.

AU - Adair, Linda S.

AU - Taylor, Herman A.

AU - Borecki, Ingrid B.

AU - Gabriel, Stacey B.

AU - Wilson, James G.

AU - Holm, Hilma

AU - Thorsteinsdottir, Unnur

AU - Gudnason, Vilmundur

AU - Krauss, Ronald M.

AU - Mohlke, Karen L.

AU - Ordovas, Jose M.

AU - Munroe, Patricia B.

AU - Kooner, Jaspal S.

AU - Tall, Alan R.

AU - Hegele, Robert A.

AU - Kastelein, John J. P.

AU - Schadt, Eric E.

AU - Rotter, Jerome I.

AU - Boerwinkle, Eric

AU - Strachan, David P.

AU - Mooser, Vincent

AU - Stefansson, Kari

AU - Reilly, Muredach P.

AU - Samani, Nilesh J.

AU - Schunkert, Heribert

AU - Cupples, L. Adrienne

AU - Sandhu, Manjinder S.

AU - Ridker, Paul M.

AU - Rader, Daniel J.

PY - 2010

Y1 - 2010

N2 - 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<-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. © 2010 Macmillan Publishers Limited. All rights reserved.

AB - 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<-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. © 2010 Macmillan Publishers Limited. All rights reserved.

U2 - https://doi.org/10.1038/nature09270

DO - https://doi.org/10.1038/nature09270

M3 - Article

C2 - 20686565

SN - 0028-0836

VL - 466

SP - 707

EP - 713

JO - NATURE

JF - NATURE

IS - 7307

ER -