Pleiotropy and genotype by diet interaction: A multivariate genetic analysis of HDL-C subfractions
- Southwest Foundation for Biomedical Research, San Antonio, TX (United States); and others
Reduced high density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease in humans. Both major genes and major genotype by diet interaction have been reported for HDL-C, but the genetics of the HDL-C subfractions are less well known. In a baboon model for human atherosclerosis, we investigated the pleiotropic effects of genes on normal quantitative variation in three HDL-C subfractions (HDL{sub 1}-C, HDL{sub 2}-C, and HDL{sub 3}-C) in two dietary environments -- a basal diet and a 7 week high cholesterol, saturated fat (HCSF) diet. We analyzed data on serum HDL-C subfraction levels, quantified by gradient gel eletrophoresis, for 942 baboons (Papo hamadryas, sensu lato) from 17 pedigrees. We used multivariate maximum likelihood methods to simultaneously estimate phenotypic means, standard deviations, and heritabilities (h{sup 2}); effects of sex, age-by-sex, age{sup 2}-by-sex, percent subspecies admixture, and infant feeding modality; plus estimated significant h{sup 2} values for all three subfractions on both diets. When tested within dietary environments, we obtained significant genetic correlations between all three subfractions [i.e., P({rho}{sub G} = 0) < 0.001] and evidence of complete pleiotropy [i.e., P({vert_bar}{rho}{sub G}{vert_bar} = 1.0) > 0.1] between HDL{sub 1}-C and HDL{sub 3}-C ({rho}{sub G} = 0.81) on the basal diet. On the HCSF diet, only the genetic correlation between HDL{sub 1}-C and HDL{sub 3}-C ({rho}{sub g} = 0.61) was significant (p > 0.1). Complete pleiotropy was observed for each of the three subfractions between both diets. Given these results, we reject genotype by diet interaction for HDL{sub 1}-C, HDL{sub 2}-C or HDL{sub 3}-C; i.e., the same genes influence variation in each subfraction to the same degree on either diet. However, the apparent disruption of pleiotropy between HDL{sub 2}-C and the other two subfractions needs to be investigated further.
- OSTI ID:
- 133914
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0648
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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