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

Tanya M. Teslovich; Kiran Musunuru; Albert V. Smith; Andrew C. Edmondson; Ioannis M. Stylianou; 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; Gonneke Willemsen; H. Erich Wichmann; John B. Whitfield; Dawn M. Waterworth; Nicholas J. Wareham; Gãrard Waeber; Peter Vollenweider; Benjamin F. Voight; Veronique Vitart; Andre G. Uitterlinden; 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; Brenda W.J.H. Penninx; 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; Nicholas G. Martin; 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; Å Johansson; Marjo Riitta Jarvelin; A. Cecile; Erik Ingelsson; Wilmar Igl; G. Kees Hovingh; Jouke Jan Hottenga; 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; Eco J.C. De Geus; Ulf De Faire; Gabriel Crawford; Francis S. Collins; Yii Der I. Chen; Mark J. Caulfield; Harry Campbell; Noel P. Burtt; Lori L. Bonnycastle; Dorret I. Boomsma; 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; Cornelia M. Van Duijn; Leena Peltonen; Gonãalo R. Abecasis; Michael Boehnke; Sekar Kathiresan

doi:10.1038/nature09270

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

Tanya M. Teslovich
, Kiran Musunuru
, Albert V. Smith
, Andrew C. Edmondson
, Ioannis M. Stylianou
, 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, Gonneke Willemsen, H. Erich Wichmann, John B. Whitfield, Dawn M. Waterworth, Nicholas J. Wareham, Gãrard Waeber, Peter Vollenweider, Benjamin F. Voight, Veronique Vitart, Andre G. Uitterlinden, 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, Brenda W.J.H. Penninx, 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, Nicholas G. Martin, 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, Å Johansson, Marjo Riitta Jarvelin, A. Cecile, Erik Ingelsson, Wilmar Igl, G. Kees Hovingh, Jouke Jan Hottenga, 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, Eco J.C. De Geus, Ulf De Faire, Gabriel Crawford, Francis S. Collins, Yii Der I. Chen, Mark J. Caulfield, Harry Campbell, Noel P. Burtt, Lori L. Bonnycastle, Dorret I. Boomsma, 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, Cornelia M. Van Duijn, Leena Peltonen, Gonãalo R. Abecasis, Michael Boehnke, Sekar Kathiresan^*

^*Corresponding author for this work

Department of Biostatistics
University of Michigan, Ann Arbor
Massachusetts General Hospital
Harvard University
Broad Institute
Johns Hopkins University
Heart Preventive Clinic
Icelandic Heart Association
University of Iceland
University of Pennsylvania
Columbia University
University of Helsinki
National Institute for Health and Welfare
Division of Preventive Medicine
Brigham and Women’s Hospital
Western University
Department of Vascular Medicine
University of Amsterdam
Erasmus University Rotterdam
Boston University
National Heart Lung and Blood Institute’s and Boston University’s Framingham Heart Study
University of Texas Health Science Center at Houston
University of Cambridge
Cardiovascular Health Research Unit
University of Washington
deCODE Genetics
Division of Statistical Genomics
Washington University St. Louis
Department of Epidemiology and Public Health
Imperial College London
Lund University
Clinical Pharmacology
Queen Mary University of London
Cedars-Sinai Medical Center
Center for Genome Science
Korea National Institute of Health
Seoul National University
Sookmyung Women's University
National University of Singapore
Agency for Science, Technology and Research, Singapore
University of North Carolina at Chapel Hill
Department of Genome Sciences
Genetics Division
GlaxoSmithKline
Division of Genetic Epidemiology
Innsbruck Medical University
University of Lübeck
University of Edinburgh
Netherlands Genomics Initiative
Department of Biological Psychology
Vrije Universiteit Amsterdam
Institute of Epidemiology
Helmholtz Zentrum München - German Research Center for Environmental Health
Genetic Epidemiology Unit
Royal Brisbane and Women's Hospital
University of Lausanne
National Research Council of Italy
University of Leicester
Clinical Research Branch
National Institutes of Health
MedStar Health
King's College London
Wellcome Trust Sanger Institute
Department of Psychiatry
VU University Medical Center
Helsinki University Hospital
Unita Operativa Geriatria
Istituto Nazionale di Riposo e Cura per Anziani - Ancona
Hammersmith Hospital
Stanford University
University of Oulu
John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre
University of Ottawa
Department of Epidemiology and Health Services
Institute of Genetic Medicine
EURAC Research
Affiliated Institute
Karolinska Institutet
Amgen Incorporated
McMaster University
Institute of Human Genetics
Technical University of Munich
University of Oxford
Oxford University Hospitals NHS Foundation Trust
University of Bristol
Institute of Applied Genomics
Municipal Institute for Medical Research Hospital del Mar
Transplantation Laboratory
University of Montreal
Laboratory of Epidemiology
Science Center
Tampere University
Institute of Regional Health Research
University of Southern Denmark
Department of Public Health
Department of Genetics and Pathology
Uppsala University
University of Regensburg
Department of Epidemiology
Aalto University
LIGHT Research Institute
University of Leeds
Department of Medicine
Department of Psychiatry
University of California at Los Angeles
University of Glasgow
Departments of Vascular Medicine and Cardiology
Amsterdam University Medical Centers
University of Southern California
Geriatric Unit
Baylor College of Medicine
Singapore National Eye Center
University of San Carlos - Philippines
Northwestern University
University of Mississippi
UCSF Benioff Children's Hospital Oakland
Department of Cardiovascular Epidemiology and Population Genetics
Centro Nacional de Investigaciones Cardiovasculares Carlos III
Nutrition and Genomics Laboratory
Tufts University
Genome Centre
Sage Bionetworks
St. George's University of London
Institute of Human Genetics

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

3159 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.

Original language	English
Pages (from-to)	707-713
Number of pages	7
Journal	Nature
Volume	466
Issue number	7307
DOIs	https://doi.org/10.1038/nature09270
Publication status	Published - 5 Aug 2010
Externally published	Yes

Access to Document

10.1038/nature09270

Cite this

Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., Johansen, C. T., Fouchier, S. W., Isaacs, A., Peloso, G. M., Barbalic, M., Ricketts, S. L., Bis, J. C., Aulchenko, Y. S., Thorleifsson, G., ... Kathiresan, S. (2010). Biological, clinical and population relevance of 95 loci for blood lipids. Nature, 466(7307), 707-713. https://doi.org/10.1038/nature09270

@article{2a202955c5c2457bb25c2018e6eaf4cc,

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.",

author = "Teslovich, \{Tanya M.\} and Kiran Musunuru and Smith, \{Albert V.\} and Edmondson, \{Andrew C.\} and Stylianou, \{Ioannis M.\} 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 Lee, \{Jong Young\} 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 Gonneke Willemsen and Wichmann, \{H. Erich\} and Whitfield, \{John B.\} and Waterworth, \{Dawn M.\} and Wareham, \{Nicholas J.\} and G{\~a}rard Waeber and Peter Vollenweider and Voight, \{Benjamin F.\} and Veronique Vitart and Uitterlinden, \{Andre G.\} 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 Penninx, \{Brenda W.J.H.\} 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 Martin, \{Nicholas G.\} and Fabio Marroni and Massimo Mangino and Magnusson, \{Patrik K.E.\} and Gavin Lucas and Robert Luben and Loos, \{Ruth J.F.\} and Lokki, \{Marja Liisa\} 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 Khaw, \{Kay Tee\} and Jaakko Kaprio and Kaplan, \{Lee M.\} and {\AA} Johansson and Jarvelin, \{Marjo Riitta\} and A. Cecile and Erik Ingelsson and Wilmar Igl and \{Kees Hovingh\}, G. and Hottenga, \{Jouke Jan\} 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 Geus\}, \{Eco J.C.\} 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 Boomsma, \{Dorret I.\} 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 Tai, \{E. Shyong\} 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.\} and \{Van Duijn\}, \{Cornelia M.\} and Leena Peltonen and Abecasis, \{Gon{\~a}alo R.\} and Michael Boehnke and Sekar Kathiresan",

year = "2010",

month = aug,

day = "5",

doi = "10.1038/nature09270",

language = "English",

volume = "466",

pages = "707--713",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7307",

}

Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, 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, JY, 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, Willemsen, G, Wichmann, HE, Whitfield, JB, Waterworth, DM, Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uitterlinden, AG, 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, Penninx, BWJH, 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, Martin, NG, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, ML, Lettre, G, Langenberg, C, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, König, IR, Khaw, KT, Kaprio, J, Kaplan, LM, Johansson, Å, Jarvelin, MR, Cecile, A, Ingelsson, E, Igl, W, Kees Hovingh, G, Hottenga, JJ, 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 Geus, EJC, De Faire, U, Crawford, G, Collins, FS, Chen, YDI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boomsma, DI, Boekholdt, SM, Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, CM, Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, ES, 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, Van Duijn, CM, Peltonen, L, Abecasis, GR, Boehnke, M & Kathiresan, S 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, Tanya M.

AU - Musunuru, Kiran

AU - Smith, Albert V.

AU - Edmondson, Andrew C.

AU - Stylianou, Ioannis M.

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 - Willemsen, Gonneke

AU - Wichmann, H. Erich

AU - Whitfield, John B.

AU - Waterworth, Dawn M.

AU - Wareham, Nicholas J.

AU - Waeber, Gãrard

AU - Vollenweider, Peter

AU - Voight, Benjamin F.

AU - Vitart, Veronique

AU - Uitterlinden, Andre G.

AU - Uda, Manuela

AU - Tuomilehto, Jaakko

AU - Thompson, John R.

AU - Tanaka, Toshiko

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AU - Boekholdt, S. Matthijs

AU - Bergman, Richard N.

AU - Barroso, Inês

AU - Bandinelli, Stefania

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AU - Assimes, Themistocles L.

AU - Quertermous, Thomas

AU - Altshuler, David

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AU - Gabriel, Stacey B.

AU - Wilson, James G.

AU - Holm, Hilma

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AU - Krauss, Ronald M.

AU - Mohlke, Karen L.

AU - Ordovas, Jose M.

AU - Munroe, Patricia B.

AU - Kooner, Jaspal S.

AU - Tall, Alan R.

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AU - Kastelein, John J.P.

AU - Schadt, Eric E.

AU - Rotter, Jerome I.

AU - Boerwinkle, Eric

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AU - Mooser, Vincent

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AU - Samani, Nilesh J.

AU - Schunkert, Heribert

AU - Cupples, L. Adrienne

AU - Sandhu, Manjinder S.

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AU - Rader, Daniel J.

AU - Van Duijn, Cornelia M.

AU - Peltonen, Leena

AU - Abecasis, Gonãalo R.

AU - Boehnke, Michael

AU - Kathiresan, Sekar

PY - 2010/8/5

Y1 - 2010/8/5

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.

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.

UR - https://www.scopus.com/pages/publications/77955505564

U2 - 10.1038/nature09270

DO - 10.1038/nature09270

M3 - Article

C2 - 20686565

AN - SCOPUS:77955505564

SN - 0028-0836

VL - 466

SP - 707

EP - 713

JO - Nature

JF - Nature

IS - 7307

ER -

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

Abstract

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