Human Molecular Genetics Advance Access published online on March 25, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh119
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medical Faculty of the Charité, Franz Volhard Clinic, HELIOS Klinikum-Berlin, Berlin, Germany
* To whom correspondence should be addressed. E-mail: luft{at}fvk-berlin.de.
Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed 6 genes and have now expanded this investigation to include 13 genes. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL) high-density cholesterol (HDL), and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model showed that the genetic variance on LDL explained 26%, on HDL explained 38%, and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL, and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%), and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%), and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%), LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.
Article
Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol
2 Bioinformatics Section, Max Delbrück Center for Molecular Medicine, Berlin, Germany
3 Gene Mapping Center, Berlin, Germany
4 Medical Faculty of the Charité, Franz Volhard Clinic, Wiltberg Strasse 50, HELIOS Klinikum-Berlin, 13125 Berlin, Germany
5 Gene Mapping Center, Berlin, Germany; Institute of Medical Genetics, Charité Universitiy Hospital, Humboldt University, Berlin, Germany
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Keebler, C. L. Sanders, A. Surti, C. Guiducci, N. P. Burtt, and S. Kathiresan Association of Blood Lipids With Common DNA Sequence Variants at 19 Genetic Loci in the Multiethnic United States National Health and Nutrition Examination Survey III Circ Cardiovasc Genet, June 1, 2009; 2(3): 238 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lu, M. E. T. Dolle, S. Imholz, R. van 't Slot, W. M. M. Verschuren, C. Wijmenga, E. J. M. Feskens, and J. M. A. Boer Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations J. Lipid Res., December 1, 2008; 49(12): 2582 - 2589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Merialdi and J. C. Murray The Changing Face of Preterm Birth Pediatrics, November 1, 2007; 120(5): 1133 - 1134. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhu, H. M. Tucker, K. E. Grear, J. F. Simpson, A. K. Manning, L. A. Cupples, and S. Estus A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol Hum. Mol. Genet., July 15, 2007; 16(14): 1765 - 1772. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Villarreal-Molina, C. A. Aguilar-Salinas, M. Rodriguez-Cruz, D. Riano, M. Villalobos-Comparan, R. Coral-Vazquez, M. Menjivar, P. Yescas-Gomez, M. Konigsoerg-Fainstein, S. Romero-Hidalgo, et al. The ATP-Binding Cassette Transporter A1 R230C Variant Affects HDL Cholesterol Levels and BMI in the Mexican Population: Association With Obesity and Obesity-Related Comorbidities Diabetes, July 1, 2007; 56(7): 1881 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Mathers and J. E. Hesketh The Biological Revolution: Understanding the Impact of SNPs on Diet-Cancer Interrelationships J. Nutr., January 1, 2007; 137(1): 253S - 258S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Reilly, A. S. Foulkes, M. L. Wolfe, and D. J. Rader Higher order lipase gene association with plasma triglycerides J. Lipid Res., September 1, 2005; 46(9): 1914 - 1922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Costanza, E. Cayanis, B. M. Ross, M. S. Flaherty, G. B. Alvin, K. Das, and A. Morabia Relative Contributions of Genes, Environment, and Interactions to Blood Lipid Concentrations in a General Adult Population Am. J. Epidemiol., April 15, 2005; 161(8): 714 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Cheng, R Huang, I S Lanham, H M Cathcart, M Howard, E H Corder, and S E Poduslo Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease J. Med. Genet., February 1, 2005; 42(2): 129 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R Thompson Is good cholesterol always good? BMJ, August 28, 2004; 329(7464): 471 - 472. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wang, D. Lan, W. Chen, F. Matsuura, and A. R. Tall ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins PNAS, June 29, 2004; 101(26): 9774 - 9779. [Abstract] [Full Text] [PDF]
|
|