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PMID: 23063622 已发表 · ppublish 英语

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

American journal of human genetics ·第 91 卷 ·第 5 期 ·2013-01-14

Asselbergs Folkert W, Guo Yiran, van Iperen Erik P A, Sivapalaratnam Suthesh, Tragante Vinicius, Lanktree Matthew B, Lange Leslie A, Almoguera Berta, Appelman Yolande E, Barnard John, Baumert Jens, Beitelshees Amber L, Bhangale Tushar R, Chen Yii-Der Ida, Gaunt Tom R, Gong Yan, Hopewell Jemma C, Johnson Toby, Kleber Marcus E, Langaee Taimour Y, Li Mingyao, Li Yun R, Liu Kiang, McDonough Caitrin W, Meijs Matthijs F L, Middelberg Rita P S, Musunuru Kiran, Nelson Christopher P, O'Connell Jeffery R, Padmanabhan Sandosh, Pankow James S, Pankratz Nathan, Rafelt Suzanne, Rajagopalan Ramakrishnan, Romaine Simon P R, Schork Nicholas J, Shaffer Jonathan, Shen Haiqing, Smith Erin N, Tischfield Sam E, van der Most Peter J, van Vliet-Ostaptchouk Jana V, Verweij Niek, Volcik Kelly A, Zhang Li, Bailey Kent R, Bailey Kristian M, Bauer Florianne, Boer Jolanda M A, Braund Peter S, Burt Amber, Burton Paul R, Buxbaum Sarah G, Chen Wei, Cooper-Dehoff Rhonda M, Cupples L Adrienne, deJong Jonas S, Delles Christian, Duggan David, Fornage Myriam, Furlong Clement E, Glazer Nicole, Gums John G, Hastie Claire, Holmes Michael V, Illig Thomas, Kirkland Susan A, Kivimaki Mika, Klein Ronald, Klein Barbara E, Kooperberg Charles, Kottke-Marchant Kandice, Kumari Meena, LaCroix Andrea Z, Mallela Laya, Murugesan Gurunathan, Ordovas Jose, Ouwehand Willem H, Post Wendy S, Saxena Richa, Scharnagl Hubert, Schreiner Pamela J, Shah Tina, Shields Denis C, Shimbo Daichi, Srinivasan Sathanur R, Stolk Ronald P, Swerdlow Daniel I, Taylor Herman A, Topol Eric J, Toskala Elina, van Pelt Joost L, van Setten Jessica, Yusuf Salim, Whittaker John C, Zwinderman A H, , Anand Sonia S, Balmforth Anthony J, Berenson Gerald S, Bezzina Connie R, Boehm Bernhard O, Boerwinkle Eric, Casas Juan P, Caulfield Mark J, Clarke Robert, Connell John M, Cruickshanks Karen J, Davidson Karina W, Day Ian N M, de Bakker Paul I W, Doevendans Pieter A, Dominiczak Anna F, Hall Alistair S, Hartman Catharina A, Hengstenberg Christian, Hillege Hans L, Hofker Marten H, Humphries Steve E, Jarvik Gail P, Johnson Julie A, Kaess Bernhard M, Kathiresan Sekar, Koenig Wolfgang, Lawlor Debbie A, März Winfried, Melander Olle, Mitchell Braxton D, Montgomery Grant W, Munroe Patricia B, Murray Sarah S, Newhouse Stephen J, Onland-Moret N Charlotte, Poulter Neil, Psaty Bruce, Redline Susan, Rich Stephen S, Rotter Jerome I, Schunkert Heribert, Sever Peter, Shuldiner Alan R, Silverstein Roy L, Stanton Alice, Thorand Barbara, Trip Mieke D, Tsai Michael Y, van der Harst Pim, van der Schoot Ellen, van der Schouw Yvonne T, Verschuren W M Monique, Watkins Hugh, Wilde Arthur A M, Wolffenbuttel Bruce H R, Whitfield John B, Hovingh G Kees, Ballantyne Christie M, Wijmenga Cisca, Reilly Muredach P, Martin Nicholas G, Wilson James G, Rader Daniel J, Samani Nilesh J, Reiner Alex P, Hegele Robert A, Kastelein John J P, Hingorani Aroon D, Talmud Philippa J, Hakonarson Hakon, Elbers Clara C, Keating Brendan J, Drenos Fotios

摘要

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.

文献信息
期刊
American journal of human genetics
期刊简称
Am J Hum Genet
发表日期
2013-01-14
收录日期
2012-11-05
更新日期
2016-11-22
语言
英语
国家/地区
United States
NLM ID
0370475
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