Exome-wide association study of plasma lipids in >300,000 individuals
2017
Online
academicJournal
Zugriff:
We screened DNA sequence variants on an exome-focused genotyping array in >300,000 participants with 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-density lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice revealed lipid changes consistent with the human data. We utilized mapped variants to address four clinically relevant questions and found the following: (1) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease; (2) outside of the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (3) only some mechanisms of lowering LDL-C seemed to increase risk for type 2 diabetes; and (4) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (e.g., TM6SF2, PNPLA3) tracked with higher liver fat, higher risk for type 2 diabetes, and lower risk for coronary artery disease whereas TG-lowering alleles involved in peripheral lipolysis (e.g., LPL, ANGPTL4) had no effect on liver fat but lowered risks for both type 2 diabetes and coronary artery disease.
| Titel: |
Exome-wide association study of plasma lipids in >300,000 individuals
|
|---|---|
| Autor/in / Beteiligte Person: | Liu, Dajiang J. ; Peloso, Gina M. ; Yu, Haojie ; Butterworth, Adam S. ; Wang, Xiao ; Mahajan, Anubha ; Saleheen, Danish ; Emdin, Connor ; Alam, Dewan ; Alves, Alexessander Couto ; Amouyel, Philippe ; di Angelantonio, Emanuele ; Arveiler, Dominique ; Assimes, Themistocles L. ; Auer, Paul L. ; Baber, Usman ; Ballantyne, Christie M. ; Bang, Lia E. ; Benn, Marianne ; Bis, Joshua C. ; Boehnke, Michael ; Boerwinkle, Eric ; Bork-Jensen, Jette ; Bottinger, Erwin P. ; Brandslund, Ivan ; Brown, Morris ; Busonero, Fabio ; Caulfield, Mark J ; Chambers, John C ; Chasman, Daniel I. ; Chen, Y. Eugene ; Chen, Yii-Der Ida ; Chowdhury, Rajiv ; Christensen, Cramer ; Chu, Audrey Y. ; Connell, John M ; Cucca, Francesco ; Cupples, L. Adrienne ; Damrauer, Scott M. ; Davies, Gail ; Deary, Ian J ; Dedoussis, George ; Denny, Joshua C. ; Dominiczak, Anna ; Dubé, Marie-Pierre ; Ebeling, Tapani ; Eiriksdottir, Gudny ; Esko, Tõnu ; Farmaki, Aliki-Eleni ; Feitosa, Mary F ; Ferrario, Marco ; Ferrieres, Jean ; Ford, Ian ; Fornage, Myriam ; Franks, Paul W. ; Frayling, Timothy M. ; Frikke-Schmidt, Ruth ; Fritsche, Lars ; Frossard, Philippe ; Fuster, Valentin ; Ganesh, Santhi K. ; Gao, Wei ; Garcia, Melissa E. ; Gieger, Christian ; Giulianini, Franco ; Goodarzi, Mark O. ; Grallert, Harald ; Grarup, Niels ; Groop, Leif ; Grove, Megan L. ; Gudnason, Vilmundur ; Hansen, Torben ; Harris, Tamara B. ; Hayward, Caroline ; Hirschhorn, Joel N. ; Holmen, Oddgeir L. ; Huffman, Jennifer ; Huo, Yong ; Hveem, Kristian ; Jabeen, Sehrish ; Jackson, Anne U ; Jakobsdottir, Johanna ; Jarvelin, Marjo-Riitta ; Jensen, Gorm B ; Jørgensen, Marit E. ; Jukema, J. Wouter ; Justesen, Johanne M. ; Kamstrup, Pia R. ; Kanoni, Stavroula ; Karpe, Fredrik ; Kee, Frank ; Khera, Amit V. ; Klarin, Derek ; Koistinen, Heikki A. ; Kooner, Jaspal S ; Kooperberg, Charles ; Kuulasmaa, Kari ; Kuusisto, Johanna ; Laakso, Markku ; Lakka, Timo ; Langenberg, Claudia ; Langsted, Anne ; Launer, Lenore J. ; Lauritzen, Torsten ; Liewald, David CM ; Lin, Li An ; Linneberg, Allan ; Loos, Ruth J.F. ; Lu, Yingchang ; Lu, Xiangfeng ; Mägi, Reedik ; Malarstig, Anders ; Manichaikul, Ani ; Manning, Alisa K. ; Mäntyselkä, Pekka ; Marouli, Eirini ; Masca, Nicholas GD ; Maschio, Andrea ; Meigs, James B. ; Melander, Olle ; Metspalu, Andres ; Morris, Andrew P ; Morrison, Alanna C. ; Mulas, Antonella ; Müller-Nurasyid, Martina ; Munroe, Patricia B. ; Neville, Matt J ; Nielsen, Jonas B. ; Nielsen, Sune F ; Nordestgaard, Børge G ; Ordovas, Jose M. ; Mehran, Roxana ; O’Donnell, Christoper J. ; Orho-Melander, Marju ; Molony, Cliona M. ; Muntendam, Pieter ; Padmanabhan, Sandosh ; Palmer, Colin NA ; Pasko, Dorota ; Patel, Aniruddh P. ; Pedersen, Oluf ; Perola, Markus ; Peters, Annette ; Pisinger, Charlotta ; Pistis, Giorgio ; Polasek, Ozren ; Poulter, Neil ; Psaty, Bruce M. ; Rader, Daniel J. ; Rasheed, Asif ; Rauramaa, Rainer ; Reilly, Dermot ; Reiner, Alex P. ; Renström, Frida ; Rich, Stephen S ; Ridker, Paul M ; Rioux, John D. ; Robertson, Neil R ; Roden, Dan M. ; Rotter, Jerome I. ; Rudan, Igor ; Salomaa, Veikko ; Samani, Nilesh J ; Sanna, Serena ; Sattar, Naveed ; Schmidt, Ellen M. ; Scott, Robert A. ; Sever, Peter ; Sevilla, Raquel S. ; Shaffer, Christian M. ; Sim, Xueling ; Sivapalaratnam, Suthesh ; Small, Kerrin S ; Smith, Albert V. ; Smith, Blair H ; Somayajula, Sangeetha ; Southam, Lorraine ; Spector, Timothy D ; Speliotes, Elizabeth K. ; Starr, John M ; Stirrups, Kathleen E ; Stitziel, Nathan ; Strauch, Konstantin ; Stringham, Heather M ; Surendran, Praveen ; Tada, Hayato ; Tall, Alan R. ; Tang, Hua ; Tardif, Jean-Claude ; Taylor, Kent D ; Trompet, Stella ; Tsao, Philip S. ; Tuomilehto, Jaakko ; Tybjaerg-Hansen, Anne ; van Zuydam, Natalie R ; Varbo, Anette ; Varga, Tibor V ; Virtamo, Jarmo ; Waldenberger, Melanie ; Wang, Nan ; Wareham, Nick J. ; Warren, Helen R ; Weeke, Peter E. ; Weinstock, Joshua ; Wessel, Jennifer ; Wilson, James G. ; Wilson, Peter W. F. ; Xu, Ming ; Yaghootkar, Hanieh ; Young, Robin ; Zeggini, Eleftheria ; Zhang, He ; Zheng, Neil S. ; Zhang, Weihua ; Zhang, Yan ; Zhou, Wei ; Zhou, Yanhua ; Zoledziewska, Magdalena ; Howson, Joanna MM ; Danesh, John ; McCarthy, Mark I ; Cowan, Chad ; Abecasis, Goncalo ; Deloukas, Panos ; Musunuru, Kiran ; Willer, Cristen J. ; Kathiresan, Sekar |
| Link: | |
| Veröffentlichung: | 2017 |
| Medientyp: | academicJournal |
| DOI: | 10.1038/ng.3977 |
| Sonstiges: |
|