Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

van Iperen, Erik P A.; van der Schouw, Yvonne T; van Vliet-Ostaptchouk, Jana V; Guo, Yiran; van Pelt, Joost L; Sivapalaratnam, Suthesh; van Setten, Jessica; Tragante, Vinicius; van Iperen, Ep P. A.; van der Most, Pj; Almoguera, Berta; van Vliet-Ostaptchouk, Jv; Barnard, John; deJong, Js S.; Baumert, Jens; van Pelt, Jl L.; de Bakker, Pi I. W.; van der Schouw, Yt T.; Gong, Yan; Asselbergs, Fw W.; Lanktree, Mb B.; Johnson, Toby; Guo, Yiran R.; Lange, La A.; Li, Mingyao Y.; Van Iperen, Epa P. A.; Appelman, Ye E.; Meijs, Matthijs F L.; Liu, Kiang A.; Middelberg, Rita P. S.; Beitelshees, Al L.; Musunuru, Kiran; Bhangale, Tr R.; Chen, Yd-Di I.; Gaunt, Tr R.; Meijs, Matthijs F. L.; O’Connell, Jeffery R.; Padmanabhan, Sandosh; Hopewell, Jc C.; Li, Yr R.; Pankratz, Nathan; Rafelt, Suzanne; Rajagopalan, Ramakrishnan; Romaine, Simon P. R.; Langaee, Ty Y.; Shaffer, Jonathan; Shen, Haiqing Q.; Kleber, Me E.; van der Most, Peter J.; Meijs, Matthijs E.-L.; OĆonnell,; Verweij, Niek; McDonough, Cw W.; Nelson, Cp P.; Zhang, Li; Bailey, Kristian M; Middelberg, Rp P. S.; Bailey, Kent R.; Pankow, Js S.; Bailey, Kent R. M.; Bauer, Florianne; O'Connell, Jeffery R.; Van Der Most, P. J.; Burt, Amber; Bailey, Kristian M R.; Chen, Wei; Van Vliet-Ostaptchouk, J.; Schork, Nj J.; Smith, En N.; Cupples, La Adrienne; Tischfield, Se E.; Delles, Christian; Romaine, Sp P. R.; Duggan, David; Fornage, Myriam; Boer, Jm; Volcik, Ka A.; Glazer, Nicole; Meijs, Mfl E.; Hastie, Claire; Braund, Ps S.; Van Setten, J.; Illig, Thomas; Cooper-Dehoff, Rm M.; Kivimaki, Mika; Klein, Ronald; Bailey, Kristian M.; Kooperberg, Charles; Middelberg, Rps; Kottke-Marchant, Kandice; Kumari, Meena; De Bakker, Piw I. W.; Mallela, Laya; Murugesan, Gurunathan; Ordovas, Jose; Burton, Pr R.; Buxbaum, Sg G.; Saxena, Richa; Adrienne Cupples, L.; Scharnagl, Hubert; Furlong, Ce E.; Shah, Tina; Bailey, Kr R.; Shimbo, Daichi; Bailey, Km M.; Srinivasan, Sathanur R.; Gums, Jg G.; Holmes, Mv; Kirkland, Sa A.; Klein, Be E.; Toskala, Elina; LaCroix, Az Z.; Stolk, Rp P.; Yusuf, Salim; Topol, Ej J.; Topo, Eric J.; Zwinderman, Ah H.; Anand, Ss Sonia S.; Ouwehand, Wh H.; Post, Ws S.; Swerdlow, Di I.; Balmforth, Aj J.; Schreiner, Pj J.; Boerwinkle, Eric; Caulfield, Mj J.; Taylor, Ha A.; Doevendans, Pa A.; Clarke, Robert; Shields, Dc C.; Berenson, Gs S.; Bezzina, Cr R.; Whittaker, Jc C.; Day, Ian N. M.; de Bakker, Paul I. W.; Dominiczak, Anna F; Dominiczak, Af E.; Dominiczak, Anna F F.; Johnson, Ja A.; Casas, Jp P.; Hengstenberg, Christian; Hall, As S.; Boehm, Bo O.; Lawlor, Da A.; Dominiczak, Anna F.; Cruickshanks, Kj J.; Jarvik, Gp P.; Connell, Jm M.; Kathiresan, Sekar; Hillege, Hl L.; Koenig, Wolfgang; Davidson, Kw W.; März, Winfried; Munroe, Pb B.; Melander, Olle; Van Der Harst, P.; Hartman, Ca A.; Newhouse, Sj J.; Murray, Ss Sarah S.; Mitchell, Bd D.; Hofker, Mh H.; Onland-Moret, Nc Charlotte; Poulter, Neil; Psaty, Bruce; Redline, Susan; Study, LifeLines Cohort; Rich, Ss Stephen S.; Rotter, Ji I.; Schunkert, Heribert; Humphries, Se E.; Sever, Peter; Day, In N. M.; Kaess, Bm M.; Stanton, Alice; Charlotte Onland Moret, N.; Thorand, Barbara; Shuldiner, Ar R.; Trip, Mieke D.; van der Harst, Pim; van der Schoot, Ellen; Montgomery, Gw W.; Tsai, My Y.; Maerz, Winfried; Whitfield, Jb B.; Verschuren, Wm M. Monique; Van Der Schoot, E.; Watkins, Hugh; Wilde, Aa Arthur A. M.; Wolffenbuttel, Bruce H R.; Silverstein, Rl L.; Hovingh, Gk Kees; Martin, Ng G.; Rader, Dj J.; Wijmenga, Cisca; Keating, Bj J.; Reilly, Muredach P.; M. Monique Verschuren, W.; Wolffenbuttel, Bh H. R.; Samani, Nj J.; Ballantyne, Cm M.; Kees Hovingh, G.; Reiner, Ap P.; Wilson, Jg G.; Kastelein, Jj John J. P.; Hingorani, Ad D.; Hegele, Ra A.; Hakonarson, Hakon; Elbers, Cc Clara C.; Talmud, Pj J.; Drenos, Fotios

Tools

Export citation

Search in Google Scholar

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

Journal article published in 2012 by Erik P A. van Iperen, Yvonne T van der Schouw

, Jana V van Vliet-Ostaptchouk, Yiran Guo, Joost L van Pelt, Suthesh Sivapalaratnam, Jessica van Setten, Vinicius Tragante, Ep P. A. van Iperen, Pj van der Most, Berta Almoguera, Jv van Vliet-Ostaptchouk, John Barnard, Js S. deJong, Jens Baumert and other authors.

This paper is available in a repository.

Full text: Download

Preprint: policy unknown

Upload

Postprint: policy unknown

Upload

Published version: policy unknown

Upload

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. © 2012 The American Society of Human Genetics.

Links

Tools

Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

Abstract