; 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 | Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | The American Journal of Human Genetics | ||||
| Publisher: | CELL PRESS | ||||
| Place of Publication: | CAMBRIDGE | ||||
| Volume: | 91 | ||||
| Number of Issue or Book Chapter: | 5 | ||||
| Page Range: | pp. 823-838 | ||||
| Date: | 2012 | ||||
| Institutions: | Medicine > Lehrstuhl für Innere Medizin II | ||||
| Identification Number: |
| ||||
| Keywords: | GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; APOLIPOPROTEIN B-100; MISSING HERITABILITY; PLASMA TRIGLYCERIDES; QUANTITATIVE TRAITS; STATISTICAL-MODEL; COMPLEX TRAITS; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 63182 |
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 ...

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 similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 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.
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