Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia

Yi Yu, Diego F. Wyszynski, Dawn M. Waterworth, Steven D. Wilton, Philip J. Barter, Y. Antero Kesäniemi, Robert W. Mahley, Ruth McPherson, Gérard Waeber, Thomas P. Bersot, Qianli Ma, Sanjay S. Sharma, Douglas S. Montgomery, Lefkos T. Middleton, Scott S. Sundseth, Vincent Mooser, Scott M Grundy, Lindsay A. Farrer

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD) = 3.34] and at 17q12 (LOD = 3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD = 3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD = 3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD = 3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD = 3.05) and on chromosome 5 in the entire group of families (LOD = 2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD = 4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD = 3.72 ). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

Original languageEnglish (US)
Pages (from-to)2202-2213
Number of pages12
JournalJournal of lipid research
Volume46
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • Cardiovascular disease
  • Epistatic effects
  • Genetic linkage analysis
  • Metabolic syndrome
  • Variance components analysis

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Yu, Y., Wyszynski, D. F., Waterworth, D. M., Wilton, S. D., Barter, P. J., Kesäniemi, Y. A., Mahley, R. W., McPherson, R., Waeber, G., Bersot, T. P., Ma, Q., Sharma, S. S., Montgomery, D. S., Middleton, L. T., Sundseth, S. S., Mooser, V., Grundy, S. M., & Farrer, L. A. (2005). Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia. Journal of lipid research, 46(10), 2202-2213. https://doi.org/10.1194/jlr.M500137-JLR200