The effect of variation in the apolipoprotein B gene on plasma lipid and apolipoprotein B levels I. A likelihood‐based approach to cladistic analysis

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Abstract
SUMMARY: A new method is described for employing family data to test for significant haplotype effects on continuously distributed variables, using likelihood‐ratio tests of linear models in which haplotype effects are parameterized and familial correlations taken into account. The method is applied to the apolipoprotein B (Apo B) gene, using 5 polymorphisms (Insertion/deletion, Bsp1286I,XbaI,MspI,EcoRI) to define haplotypes in 121 French nuclear families. Eleven haplotypes were found, five of which, combined, account for over 95% of the sample. A haplotype phylogeny is proposed, and is used to define a nested set of models for testing the effects of Apo B variation on total‐, low‐density‐lipoprotein (LDL)‐, and high‐density ‐lipoprotein (HDL)‐cholesterol, triglyceride, and Apo B levels. Apo B haplotype effects account for about 10% of the genetic variance and 5% of the total variance in HDL‐cholesterol and triglyceride levels. Clusters of evolutionarily‐related haplotypes with similar phenotypic effects are identified for HDL‐cholesterol and triglycerides. Single haplotypes with statistically significant effects are identified for cholesterol, LDL‐cholesterol, and Apo B levels.