2017
article
Exome-wide association study of plasma lipids in > 300,000 individuals
Dajiang J. Liu, Gina Marie Peloso, Haojie Yu, Adam S. Butterworth, Xiao Wang, Anubha Mahajan, Danish Saleheen, Connor A. Emdin, Dewan Shamsul Alam, Alexessander Couto Alves, Philippe Amouyel, Emanuele Di Angelantonio, Dominique Arveiler, Themistocles L. Assimes, Paul Livermore Auer, Usman Baber, Christie Mitchell Ballantyne, Lia Evi Bang, Marianne Benn, Joshua C. Bis, Michael Boehnke, Eric Boerwinkle, Jette Bork‐Jensen, Erwin P. Böttinger, Ivan Brandslund, Morris Jonathan Brown, Fabio Busonero, Mark J. Caulfield, John Campbell Chambers, Daniel I. Chasman, Y. Eugene Chen, Yii‐Der Ida Chen, Rajiv Chowdhury, Cramer Christensen, Audrey Y. Chu, John Connell, Francesco Cucca, L. Adrienne Cupples, Scott M. Damrauer, Gail Davies, Ian J. Deary, George V. Dedoussis, Joshua C. Denny, Anna F. Dominiczak, Marie‐Pierre Dubé, Tapani Ebeling, Guðný Eiríksdóttir, Tõnu Esko, Aliki‐Eleni Farmaki, Mary Furlan Feitosa, Maurizio Ferrario, Jean Ferrières, Ian Ford, Myriam Fornage, Paul W. Franks, Timothy Mark Frayling, Ruth Frikke‐Schmidt, Lars G. Fritsche, Philippe Frossard, Valentı́n Fuster, Santhi K. Ganesh, Wei Gao, Melissa E. Garcia, Christian Gieger, Franco Giulianini, Mark O. Goodarzi, Harald Grallert, Niels Grarup, Leif Groop, Megan L. Grove, Vilmundur G. Gudnason, Torben F. Hansen, Tamara B. Harris, Caroline Hayward, Joel N. Hirschhorn, Oddgeir L. Holmen, Jennifer E. Huffman, Yong Jiu Huo, Kristian Hveem, Sehrish Jabeen, Anne Jackson, Jóhanna Jakobsdóttir, Marjo‐Riitta Järvelin, Gorm Boje Jensen, Marit E. Jørgensen, J. Wouter Jukema, Johanne Marie Justesen, Pia R. Kamstrup, Stavroula Kanoni, Fredrik Karpe, Frank Kee, Amit Khera, Derek M. Klarin, Heikki A. Koistinen, Jaspal Singh Kooner, Charles L Kooperberg, Kari Kuulasmaa, Johanna Kuusisto, Markku Laakso, Timo Antero Lakka, Claudia Langenberg, Anne Langsted, Lenore J. Launer, Torsten Lauritzen, David C M Liewald, Li An Lin, Allan R Linneberg, Ruth J. F. Loos, Yingchang Lu, Xiangfeng Lu, Reedik Mägi, Anders Mälarstig, Ani W Manichaikul, Alisa Knodle Manning, Pekka T Mäntyselkä, Eirini Marouli, Nicholas G. D. Masca, Andrea Maschio, James B. Meigs, Olle Melander, Andres Metspalu, Andrew Paul Morris, Alanna C. Morrison, Antonella Mulas, Martina Müller‐Nurasyid, Patricia B. Munroe, Matt J. Neville, Jonas Bille Nielsen, Sune Fallgaard Nielsen, Børge Grønne Nordestgaard, José María Ordovás, Roxana Mehran, Christoper J. O'Donnell, Marju Orho‐Melander, Cliona M. Molony, Pieter Muntendam, Sandosh Padmanabhan, Dorota Pasko, Aniruddh P. Patel, Oluf Borbye Pedersen, Markus Perola, Annette Peters, Charlotta Holm Pisinger, Giorgio Pistis, Ozren Polašek, Neil Poulter, Bruce M. Psaty, Daniel James Rader, Asif Rasheed, Rainer Rauramaa, Dermot F. Reilly, Alex P. Reiner, Frida Renström, Stephen S. Rich, Paul M. Ridker, John David Rioux, Neil R. Robertson, Dan M. Roden, Jerome I. Rotter, Igor Rudan, Veikko V Salomaa, Nilesh J. Samani, Serena Sanna, Naveed A. Sattar, Ellen M. Schmidt, Robert A. Scott, Peter Sever, Raquel Sanabrias Fernández de Sevilla, Christian M. Shaffer, Xueling Sim, Suthesh Sivapalaratnam, Kerrin S. Small, Albert V. Smith, Blair Hamilton Smith, Sangeetha Somayajula, Lorraine Southam, Timothy D. Spector, Elizabeth K. Speliotes, John M. Starr, Kathleen E. Stirrups, Nathan O. Stitziel, Konstantin Strauch, Heather M. Stringham, Praveen Surendran, Hayato Tada, Alan R. Tall, Hua Tang, Jean‐Claude Tardif, Kent D. Taylor, Stella Trompet, Philip S. Tsao, Jaakko Tuomilehto, Anne Tybjærg‐Hansen, Natalie R. van Zuydam, Anette Varbo, Tibor V. Varga, Jarmo R. K. Virtamo, Mélanie Waldenberger, Nan Wang, Nicholas J. Wareham, Helen R. Warren, Peter Ejvin Weeke, Joshua S. Weinstock, Jennifer Wessel, James G. Wilson, Peter W.F. Wilson, Ming Xu, Hanieh Yaghootkar, Robin Young, Eleftheria Zeggini, He Zhang, NingNing Zheng, Weihua Zhang, Yan Zhang, Wei Zhou, Yanhua Zhou, Magdalena Żołędziewska, Joanna M. M. Howson, John Danesh, Mark I. McCarthy, Chad A. Cowan, Gonçalo R. Abecasis, Panos Deloukas, Yan V. Sun, Cristen J. Willer, Sekar Kathiresan
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Le résumé fourni par la source
We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TGrich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
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Les sujets associés
Liver Disease Diagnosis and TreatmentGenetic Associations and EpidemiologyFolate and B Vitamins Research