Pleiotropy and Genotype by Diet Interaction in a Baboon Model for Atherosclerosis

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Abstract —We investigated dietary effects on pleiotropic relationships among 3 HDL cholesterol (C) subfractions (HDL 1 -C, HDL 2 -C, and HDL 3 -C; levels quantified by gradient gel electrophoresis) for 942 pedigreed baboons ( Papio hamadryas ) who were fed a basal (Chow) diet and a high cholesterol, saturated fat (HCSF) challenge diet. Using multivariate maximum likelihood methods we estimated heritabilities for all 6 traits, genetic and environmental correlations (ρ G and ρ E ) between them, and the additive genetic variance of each subfraction’s response to the diets. On the Chow diet, genetic correlations between the 3 subfractions were significant, and we observed complete pleiotropy between HDL 1 -C and HDL 3 -C (ρ G =−0.81). On the HCSF diet, only the genetic correlation between HDL 1 -C and HDL 3 -C (ρ G =−0.61) was significant. Genetic correlations between individual subfractions on the Chow and HCSF diets did not differ significantly from 1.0, indicating that the same additive genes influenced each subfraction’s levels regardless of diet. However, the additive genetic variance of response to the diets was highly significant for HDL 1 -C and HDL 2 -C, but not for HDL 3 -C. Similar sets of genes influence variation in the 3 HDL subfractions on the Chow diet, and the same set influences variation in each subfraction on the HCSF diet. However, the expression of genes influencing HDL 1 -C and HDL 2 -C is altered by the HCSF diet, disrupting the pleiotropy observed between the 3 subfractions on the Chow diet.

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