The effect of variation in the apolipoprotein B gene on plasmid lipid and apolipoprotein B levels. I. A likelihood-based approach to cladistic analysis.
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.
Center for Demographic and Population Genetics, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston 77225.
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DM
Hallman
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Visvikis
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J
Steinmetz
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E
Boerwinkle
D000293:Adolescent; D000328:Adult; D001055:Apolipoproteins B / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D005260:Female; D005602:France; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic
D001055:Apolipoproteins B; D008055:Lipids