Human Genetics

, Volume 113, Issue 6, pp 522–533

Evidence of linkage of HDL level variation to APOC3 in two samples with different ascertainment

  • France Gagnon
  • Gail P. Jarvik
  • Arno G. Motulsky
  • Samir S. Deeb
  • John D. Brunzell
  • Ellen M. Wijsman
Original Investigation

DOI: 10.1007/s00439-003-1006-5

Cite this article as:
Gagnon, F., Jarvik, G.P., Motulsky, A.G. et al. Hum Genet (2003) 113: 522. doi:10.1007/s00439-003-1006-5

Abstract

The APOA1-C3-A4-A5 gene complex encodes genes whose products are implicated in the metabolism of HDL and/or triglycerides. Although the relationship between polymorphisms in this gene cluster and dyslipidemias was first reported more than 15 years ago, association and linkage results have remained inconclusive. This is due, in part, to the oligogenic and multivariate nature of dyslipidemic phenotypes. Therefore, we investigate evidence of linkage of APOC3 and HDL using two samples of dyslipidemic pedigrees: familial combined hyperlipidemia (FCHL) and isolated low-HDL (ILHDL). We used a strategy that deals with several difficulties inherent in the study of complex traits: by using a Bayesian Markov Chain Monte Carlo (MCMC) approach we allow for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. By using this approach on extended pedigrees we provide evidence of linkage of APOC3 and HDL level variation in two samples with different ascertainment. In addition to APOC3, we estimate that two to three genes, each with a substantial effect on total variance, are responsible for HDL variation in both data sets. We also provide evidence, using the FCHL data set, for a pleiotropic effect between HDL, HDL3 and triglycerides at the APOC3 locus.

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • France Gagnon
    • 1
    • 2
  • Gail P. Jarvik
    • 2
    • 3
  • Arno G. Motulsky
    • 2
    • 3
  • Samir S. Deeb
    • 2
    • 3
  • John D. Brunzell
    • 4
  • Ellen M. Wijsman
    • 2
    • 3
    • 5
  1. 1.Department of Epidemiology and Community MedicineUniversity of OttawaOttawaCanada
  2. 2.Division of Medical Genetics, Department of MedicineUniversity of WashingtonSeattleUSA
  3. 3.Department of Genome SciencesUniversity of WashingtonSeattleUSA
  4. 4.Division of Metabolism and Endocrinology, Department of MedicineUniversity of WashingtonSeattleUSA
  5. 5.Department of BiostatisticsUniversity of WashingtonSeattleUSA