Pleiotropic QTL on chromosome 12q23-q24 influences triglyceride and high-density lipoprotein cholesterol levels: The HERITAGE family study

Mary F. Feitosa, Treva Rice, Ingrid B. Borecki, Tuomo Rankinen, Arthur S. Leon, James S. Skinner, Jean Pierre Després, John Blangero, Claude Bouchard, D. C. Rao

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

To determine whether a common quantitative trait locus (QTL) influences the variation of fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels, we used a bivariate multipoint linkage analysis with 654 polymorphic markers in 99 white and 101 black families. The phenotypes were investigated under two conditions: at baseline and after a 20-week exercise training intervention. A maximum genome-wide bivariate LOD score of 3.0 (p = 0.00010) was found on chromosome 12q23-q24, located within the IGF1 gene (insulin-like growth factor 1, at 107 cM) for TG and HDL-C at baseline in whites. This bivariate linkage peak is considerably higher than the univariate linkage results at the same chromosome location for either trait (for TG, LOD = 2.07, p = 0.00108; for HDL-C, LOD = 2.04, p = 0.00101). The genetic correlations between baseline TG and HDL-C levels were -0.14 for the residual and -0.33 for the QTL components. Moreover, association analysis showed that TG, HDL-C, and IGFI are significantly associated (p = 0.04). In conclusion, these results suggest that a QTL on chromosome 12q23-q24 influences the variation of plasma TG and HDL-C levels. Further investigation should confirm whether IGFI or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.

Original languageEnglish (US)
Pages (from-to)317-327
Number of pages11
JournalHuman Biology
Volume78
Issue number3
DOIs
StatePublished - Jun 2006

Keywords

  • Bivariate linkage analysis
  • Coronary heart disease
  • High-density lipoprotein (HDL)
  • Insulin-like growth factor 1 (IGF1)
  • Lipid
  • Lipoprotein
  • Quantitative trait loci
  • Triglycerides

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