| Literature DB >> 23063622 |
Folkert W Asselbergs1, Yiran Guo, Erik P A van Iperen, Suthesh Sivapalaratnam, Vinicius Tragante, Matthew B Lanktree, Leslie A Lange, Berta Almoguera, Yolande E Appelman, John Barnard, Jens Baumert, Amber L Beitelshees, Tushar R Bhangale, Yii-Der Ida Chen, Tom R Gaunt, Yan Gong, Jemma C Hopewell, Toby Johnson, Marcus E Kleber, Taimour Y Langaee, Mingyao Li, Yun R Li, Kiang Liu, Caitrin W McDonough, Matthijs F L Meijs, Rita P S Middelberg, Kiran Musunuru, Christopher P Nelson, Jeffery R O'Connell, Sandosh Padmanabhan, James S Pankow, Nathan Pankratz, Suzanne Rafelt, Ramakrishnan Rajagopalan, Simon P R Romaine, Nicholas J Schork, Jonathan Shaffer, Haiqing Shen, Erin N Smith, Sam E Tischfield, Peter J van der Most, Jana V van Vliet-Ostaptchouk, Niek Verweij, Kelly A Volcik, Li Zhang, Kent R Bailey, Kristian M Bailey, Florianne Bauer, Jolanda M A Boer, Peter S Braund, Amber Burt, Paul R Burton, Sarah G Buxbaum, Wei Chen, Rhonda M Cooper-Dehoff, L Adrienne Cupples, Jonas S deJong, Christian Delles, David Duggan, Myriam Fornage, Clement E Furlong, Nicole Glazer, John G Gums, Claire Hastie, Michael V Holmes, Thomas Illig, Susan A Kirkland, Mika Kivimaki, Ronald Klein, Barbara E Klein, Charles Kooperberg, Kandice Kottke-Marchant, Meena Kumari, Andrea Z LaCroix, Laya Mallela, Gurunathan Murugesan, Jose Ordovas, Willem H Ouwehand, Wendy S Post, Richa Saxena, Hubert Scharnagl, Pamela J Schreiner, Tina Shah, Denis C Shields, Daichi Shimbo, Sathanur R Srinivasan, Ronald P Stolk, Daniel I Swerdlow, Herman A Taylor, Eric J Topol, Elina Toskala, Joost L van Pelt, Jessica van Setten, Salim Yusuf, John C Whittaker, A H Zwinderman, Sonia S Anand, Anthony J Balmforth, Gerald S Berenson, Connie R Bezzina, Bernhard O Boehm, Eric Boerwinkle, Juan P Casas, Mark J Caulfield, Robert Clarke, John M Connell, Karen J Cruickshanks, Karina W Davidson, Ian N M Day, Paul I W de Bakker, Pieter A Doevendans, Anna F Dominiczak, Alistair S Hall, Catharina A Hartman, Christian Hengstenberg, Hans L Hillege, Marten H Hofker, Steve E Humphries, Gail P Jarvik, Julie A Johnson, Bernhard M Kaess, Sekar Kathiresan, Wolfgang Koenig, Debbie A Lawlor, Winfried März, Olle Melander, Braxton D Mitchell, Grant W Montgomery, Patricia B Munroe, Sarah S Murray, Stephen J Newhouse, N Charlotte Onland-Moret, Neil Poulter, Bruce Psaty, Susan Redline, Stephen S Rich, Jerome I Rotter, Heribert Schunkert, Peter Sever, Alan R Shuldiner, Roy L Silverstein, Alice Stanton, Barbara Thorand, Mieke D Trip, Michael Y Tsai, Pim van der Harst, Ellen van der Schoot, Yvonne T van der Schouw, W M Monique Verschuren, Hugh Watkins, Arthur A M Wilde, Bruce H R Wolffenbuttel, John B Whitfield, G Kees Hovingh, Christie M Ballantyne, Cisca Wijmenga, Muredach P Reilly, Nicholas G Martin, James G Wilson, Daniel J Rader, Nilesh J Samani, Alex P Reiner, Robert A Hegele, John J P Kastelein, Aroon D Hingorani, Philippa J Talmud, Hakon Hakonarson, Clara C Elbers, Brendan J Keating, Fotios Drenos.
Abstract
Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.Entities:
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Year: 2012 PMID： 23063622 PMCID： PMC3487124 DOI： 10.1016/j.ajhg.2012.08.032
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025