Quantitative Trait Loci for Apolipoprotein B, Cholesterol, and Triglycerides in Familial Combined Hyperlipidemia Pedigrees

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Abstract
Objective— Familial combined hyperlipidemia (FCHL) is a genetically complex lipid disorder that is diagnosed in families by combinations of increased cholesterol, triglycerides, and/or apolipoprotein B (apoB) levels in patients and their first-degree relatives. Identifying the predisposing genes promises to reveal the primary risk factors and susceptibility pathways and suggest methods of prevention and treatment. As with most genetically complex disorders, a clinical definition of disease may not be the most useful phenotype for finding the complement of predisposing genes, and the quantitative traits used to define the disorder can provide important information. This is a report of a quantitative trait loci (QTL) analysis of FCHL. Methods and Results— A full genome scan of 377 multi-allelic markers genotyped at ≈10 centimorgan (cM) intervals was conducted in 150 sibling pairs from 22 nuclear families in FCHL pedigrees. These data were analyzed by 2 multipoint QTL linkage methods using the nonparametric and Haseman–Elston procedures of the Genehunter software. Using a criterion of P P P P P P P P P P P P Conclusions— QTL analyses of the traits that define FCHL are effective for localizing disease-predisposing genes.

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