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Discovery and Refinement of Loci Associated with Lipid Levels

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 188,578 individuals using...

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Detalles Bibliográficos
Autores principales: Willer, Cristen J., Schmidt, Ellen M., Sengupta, Sebanti, Peloso, Gina M., Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L., Mora, Samia, Beckmann, Jacques S., Bragg-Gresham, Jennifer L., Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M., Do, Ron, Donnelly, Louise A., Ehret, Georg B., Esko, Tõnu, Feitosa, Mary F., Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Fraser, Ross M., Freitag, Daniel F., Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U., Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E., Li, Xiaohui, Luan, Jian’an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K.E., Mangino, Massimo, Mihailov, Evelin, Montasser, May E., Müller-Nurasyid, Martina, Nolte, Ilja M., O’Connell, Jeffrey R., Palmer, Cameron D., Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K., Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J., Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M., Thorleifsson, Gudmar, Van den Herik, Evita G., Voight, Benjamin F., Volcik, Kelly A., Waite, Lindsay L., Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F., Bolton, Jennifer L., Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S., Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S.F., Döring, Angela, Elliott, Paul, Epstein, Stephen E., Ingi Eyjolfsson, Gudmundur, Gigante, Bruna, Goodarzi, Mark O., Grallert, Harald, Gravito, Martha L., Groves, Christopher J., Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A., Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R., Kaleebu, Pontiano, Kastelein, John J.P., Khaw, Kay-Tee, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimäki, Terho, Lin, Shih-Yi, Lindström, Jaana, Loos, Ruth J.F., Mach, François, McArdle, Wendy L, Meisinger, Christa, Mitchell, Braxton D., Müller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V.M., Nsubuga, Rebecca N., Olafsson, Isleifur, Ong, Ken K., Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J., Reilly, Muredach P., Ridker, Paul M., Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J., Tiret, Laurence, Uitterlinden, Andre G., van Pelt, L. Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H., Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F., Young, Elizabeth H., Zhao, Jing Hua, Adair, Linda S., Arveiler, Dominique, Assimes, Themistocles L., Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O., Boomsma, Dorret I., Borecki, Ingrid B., Bornstein, Stefan R., Bovet, Pascal, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C., Chen, Yii-Der Ida, Collins, Francis S., Cooper, Richard S., Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B., Ferrières, Jean, Ferrucci, Luigi, Freimer, Nelson B., Gieger, Christian, Groop, Leif C., Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B., Hingorani, Aroon, Hirschhorn, Joel N., Hofman, Albert, Hovingh, G. Kees, Hsiung, Chao Agnes, Humphries, Steve E., Hunt, Steven C., Hveem, Kristian, Iribarren, Carlos, Järvelin, Marjo-Riitta, Jula, Antti, Kähönen, Mika, Kaprio, Jaakko, Kesäniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S., Koudstaal, Peter J., Krauss, Ronald M., Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O., Laakso, Markku, Lakka, Timo A., Lind, Lars, Lindgren, Cecilia M., Martin, Nicholas G., März, Winfried, McCarthy, Mark I., McKenzie, Colin A., Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D., Munroe, Patricia B., Njølstad, Inger, Pedersen, Nancy L., Power, Chris, Pramstaller, Peter P., Price, Jackie F., Psaty, Bruce M., Quertermous, Thomas, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K., Saramies, Jouko, Schwarz, Peter E.H., Sheu, Wayne H-H, Shuldiner, Alan R., Siegbahn, Agneta, Spector, Tim D., Stefansson, Kari, Strachan, David P., Tayo, Bamidele O., Tremoli, Elena, Tuomilehto, Jaakko, Uusitupa, Matti, van Duijn, Cornelia M., Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J., Whitfield, John B., Wolffenbuttel, Bruce H.R., Ordovas, Jose M., Boerwinkle, Eric, Palmer, Colin N.A., Thorsteinsdottir, Unnur, Chasman, Daniel I., Rotter, Jerome I., Franks, Paul W., Ripatti, Samuli, Cupples, L. Adrienne, Sandhu, Manjinder S., Rich, Stephen S., Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L., Ingelsson, Erik, Abecasis, Gonçalo R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838666/
https://www.ncbi.nlm.nih.gov/pubmed/24097068
http://dx.doi.org/10.1038/ng.2797
Descripción
Sumario: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 188,578 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 lipids 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 illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.