Discovery and refinement of loci associated with lipid levels

Cristen J. Willer, Ellen M. Schmidt, Sebanti Sengupta, Gina M. Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Jin Chen, Martin L. Buchkovich, Samia Mora, Jacques S. Beckmann, Jennifer L. Bragg-Gresham, Hsing Yi Chang, Ayse Demirkan, Heleen M. Den Hertog, Ron Do, Louise A. Donnelly, Georg B. Ehret, Tõnu Esko, Mary F. FeitosaTeresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M. Fraser, Daniel F. Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne U. Jackson, Åsa Johansson, Toby Johnson, Marika Kaakinen, Johannes Kettunen, Marcus E. Kleber, Xiaohui Li, Jian'an Luan, Leo Pekka Lyytikäinen, Patrik K.E. Magnusson, Massimo Mangino, Evelin Mihailov, May E. Montasser, Martina Müller-Nurasyid, Ilja M. Nolte, Jeffrey R. O'Connell, Cameron D. Palmer, Markus Perola, Ann Kristin Petersen, Serena Sanna, Richa Saxena, Susan K. Service, Sonia Shah, Dmitry Shungin, Carlo Sidore, Ci Song, Rona J. Strawbridge, Ida Surakka, Toshiko Tanaka, Tanya M. Teslovich, Gudmar Thorleifsson, Evita G. Van Den Herik, Benjamin F. Voight, Kelly A. Volcik, Lindsay L. Waite, Andrew Wong, Ying Wu, Weihua Zhang, Devin Absher, Gershim Asiki, Inês Barroso, Latonya F. Been, Jennifer L. Bolton, Lori L. Bonnycastle, Paolo Brambilla, Mary S. Burnett, Giancarlo Cesana, Maria Dimitriou, Alex S.F. Doney, Angela Döring, Paul Elliott, Stephen E. Epstein, Gudmundur Ingi Eyjolfsson, Bruna Gigante, Mark O. Goodarzi, Harald Grallert, Martha L. Gravito, Christopher J. Groves, Göran Hallmans, Anna Liisa Hartikainen, Caroline Hayward, Dena Hernandez, Andrew A. Hicks, Hilma Holm, Yi Jen Hung, Thomas Illig, Michelle R. Jones, Pontiano Kaleebu, John J.P. Kastelein, Kay Tee Khaw, Eric Kim, Norman Klopp, Pirjo Komulainen, Meena Kumari, Claudia Langenberg, Terho Lehtimäki, Shih Yi Lin, Jaana Lindström, Ruth J.F. Loos, François Mach, Wendy L. McArdle, Christa Meisinger, Braxton D. Mitchell, Gabrielle Müller, Ramaiah Nagaraja, Narisu Narisu, Tuomo V.M. Nieminen, Rebecca N. Nsubuga, Isleifur Olafsson, Ken K. Ong, Aarno Palotie, Theodore Papamarkou, Cristina Pomilla, Anneli Pouta, Daniel J. Rader, Muredach P. Reilly, Paul M. Ridker, Fernando Rivadeneira, Igor Rudan, Aimo Ruokonen, Nilesh Samani, Hubert Scharnagl, Janet Seeley, Kaisa Silander, Alena Stancáková, Kathleen Stirrups, Amy J. Swift, Laurence Tiret, Andre G. Uitterlinden, L. Joost Van Pelt, Sailaja Vedantam, Nicholas Wainwright, Cisca Wijmenga, Sarah H. Wild, Gonneke Willemsen, Tom Wilsgaard, James F. Wilson, Elizabeth H. Young, Jing Hua Zhao, Linda S. Adair, Dominique Arveiler, Themistocles L. Assimes, Stefania Bandinelli, Franklyn Bennett, Murielle Bochud, Bernhard O. Boehm, Dorret I. Boomsma, Ingrid B. Borecki, Stefan R. Bornstein, Pascal Bovet, Michel Burnier, Harry Campbell, Aravinda Chakravarti, John C. Chambers, Yii Der Ida Chen, Francis S. Collins, Richard S. Cooper, John Danesh, George Dedoussis, Ulf De Faire, Alan B. Feranil, Jean Ferrières, Luigi Ferrucci, Nelson B. Freimer, Christian Gieger, Leif C. Groop, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Tamara B. Harris, Aroon Hingorani, Joel N. Hirschhorn, Albert Hofman, G. Kees Hovingh, Chao Agnes Hsiung, Steve E. Humphries, Steven Hunt, Kristian Hveem, Carlos Iribarren, Marjo Riitta Järvelin, Antti Jula, Mika Kähönen, Jaakko Kaprio, Antero Kesäniemi, Mika Kivimaki, Jaspal S. Kooner, Peter J. Koudstaal, Ronald M. Krauss, Diana Kuh, Johanna Kuusisto, Kirsten O. Kyvik, Markku Laakso, Timo A. Lakka, Lars Lind, Cecilia M. Lindgren, Nicholas G. Martin, Winfried März, Mark I. McCarthy, Colin A. McKenzie, Pierre Meneton, Andres Metspalu, Leena Moilanen, Andrew D. Morris, Patricia B. Munroe, Inger Njølstad, Nancy L. Pedersen, Chris Power, Peter P. Pramstaller, Jackie F. Price, Bruce M. Psaty, Thomas Quertermous, Rainer Rauramaa, Danish Saleheen, Veikko Salomaa, Dharambir K. Sanghera, Jouko Saramies, Peter E.H. Schwarz, Wayne H.H. Sheu, Alan R. Shuldiner, Agneta Siegbahn, Tim D. Spector, Kari Stefansson, David P. Strachan, Bamidele O. Tayo, Elena Tremoli, Jaakko Tuomilehto, Matti Uusitupa, Cornelia M. Van Duijn, Peter Vollenweider, Lars Wallentin, Nicholas J. Wareham, John B. Whitfield, Bruce H.R. Wolffenbuttel, Jose M. Ordovas, Eric Boerwinkle, Colin N.A. Palmer, Unnur Thorsteinsdottir, Daniel I. Chasman, Jerome I. Rotter, Paul W. Franks, Samuli Ripatti, L. Adrienne Cupples, Manjinder S. Sandhu, Stephen S. Rich, Michael Boehnke, Panos Deloukas, Sekar Kathiresan, Karen L. Mohlke, Erik Ingelsson, Gonçalo R. Abecasis

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Abstract

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10 -8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

Original languageEnglish
Pages (from-to)1274-1285
Number of pages12
JournalNature Genetics
Volume45
Issue number11
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Willer, C. J., Schmidt, E. M., Sengupta, S., Peloso, G. M., Gustafsson, S., Kanoni, S., Ganna, A., Chen, J., Buchkovich, M. L., Mora, S., Beckmann, J. S., Bragg-Gresham, J. L., Chang, H. Y., Demirkan, A., Den Hertog, H. M., Do, R., Donnelly, L. A., Ehret, G. B., Esko, T., ... Abecasis, G. R. (2013). Discovery and refinement of loci associated with lipid levels. Nature Genetics, 45(11), 1274-1285. https://doi.org/10.1038/ng.2797