Common variants associated with plasma triglycerides and risk for coronary artery disease

Ron Do, Cristen J. Willer, Ellen M. Schmidt, Sebanti Sengupta, Chi Gao, 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, Louise A. Donnelly, Georg B. Ehret, Tõnu EskoMary F. Feitosa, Teresa 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 C. 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, David Altshuler, 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, Karen L. Mohlke, Erik Ingelsson, Goncalo R. Abecasis, Mark J. Daly, Benjamin M. Neale, Sekar Kathiresan

Research output: Contribution to journalLetter

Abstract

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10 -8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Original languageEnglish (US)
Pages (from-to)1345-1353
Number of pages9
JournalNature genetics
Volume45
Issue number11
DOIs
StatePublished - Nov 1 2013

    Fingerprint

ASJC Scopus subject areas

  • Genetics

Cite this

Do, R., Willer, C. J., Schmidt, E. M., Sengupta, S., Gao, C., 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., Donnelly, L. A., Ehret, G. B., ... Kathiresan, S. (2013). Common variants associated with plasma triglycerides and risk for coronary artery disease. Nature genetics, 45(11), 1345-1353. https://doi.org/10.1038/ng.2795