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Discovery and refinement of loci associated with lipid levels

2013; Nature Portfolio; Volume: 45; Issue: 11 Linguagem: Inglês

10.1038/ng.2797

1546-1718

Cristen J. Willer, Ellen M. Schmidt, Sebanti Sengupta, Gina M. Peloso, Stefan Gustafsson, Stavroula Kanoni, Andrea Ganna, Ming‐Huei Chen, Martin L. Buchkovich, Samia Mora, J. Beckmann, Jennifer L. Bragg‐Gresham, Hsing‐Yi Chang, Ayşe Demirkan, Heleen M. den Hertog, Ron Do, Louise A. Donnelly, Georg Ehret, Tõnu Esko, Mary F. Feitosa, Teresa Ferreira, Krista Fischer, Pierre Fontanillas, Ross M. Fraser, Daniel F. Freitag, Deepti Gurdasani, Kauko Heikkilä, Elina Hyppönen, Aaron Isaacs, Anne 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, Guðmar Þorleifsson, 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 Been, Jennifer L. Bolton, Lori L. Bonnycastle, Paolo Brambilla, Mary Susan Burnett, Giancarlo Cesana, Maria Dimitriou, Alex S. F. Doney, Angela Döring, Paul Elliott, Stephen E. Epstein, Guðmundur I. Eyjólfsson, Bruna Gigante, Mark O. Goodarzi, Harald Grallert, Martha L. Gravito, Christopher J. Groves, Göran Hallmans, Anna-Liisa Hartikainen, Caroline Hayward, Dena Hernández, Andrew A. Hicks, Hilma Hólm, Yi-Jen Hung, Thomas Illig, Michelle R. Jones, Pontiano Kaleebu, John J.P. Kastelein, Kay‐Tee Khaw, Eric H. 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 Nieminen, Rebecca N. Nsubuga, Ísleifur Ólafsson, 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 J. Samani, Hubert Scharnagl, Janet Seeley, Kaisa Silander, Alena Stančáková, Kathleen Stirrups, Amy J. Swift, Laurence Tiret, André G. Uitterlinden, L. Joost van Pelt, Sailaja Vedantam, Nicholas W.J. Wainwright, Cisca Wijmenga, Sarah H. Wild, Gonneke Willemsen, Tom Wilsgaard, James F. Wilson, Elizabeth Young, Jing Hua Zhao, Linda S. Adair, Dominique Arveiler, Themistocles L. Assimes, Stefania Bandinelli, Franklyn I. 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, Stephen S. Rich, John Danesh, George Dedoussis, Ulf dé Fairé, Alan B. Feranil, Jean Ferrières, Luigi Ferrucci, Nelson B. Freimer, Christian Gieger, Leif Groop, Vilmundur Guðnason, Ulf Gyllensten, Anders Hamsten, Tamara B. Harris, Aroon D. Hingorani, Joel N. Hirschhorn, Albert Hofman, G. Kees Hovingh, Chao A. Hsiung, Steve E. Humphries, Steven C. Hunt, Kristian Hveem, Carlos Iribarren, Marjo‐Riitta Järvelin, Antti Jula, Mika Kähönen, Jaakko Kaprio, Antero Kesäniemi, Mika Kivimäki, Jaspal S. Kooner, Peter J. Koudstaal, Ronald M. Krauss, Diana Kuh, Johanna Kuusisto, Kirsten Ohm 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, Kāri Stefánsson, David P. Strachan, Bamidele O. Tayo, Elena Tremoli, Jaakko Tuomilehto, Matti Uusitupa, Cornelia M. van Duijn, Péter Vollenweider, Lars Wallentin, Nicholas J. Wareham, John B. Whitfield, Bruce H. R. Wolffenbuttel, José M. Ordovás, Eric Boerwinkle, Colin N. A. Palmer, Unnur Þorsteinsdóttir, 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,

Genetic and phenotypic traits in livestock

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.