A MAJOR LOCUS INFLUENCING PLASMA HIGH-DENSITY-LIPOPROTEIN CHOLESTEROLLEVELS IN THE SAN-ANTONIO FAMILY HEART-STUDY - SEGREGATION AND LINKAGE ANALYSES

To detect and measure the effects of a single locus on quantitative va riation in plasma concentrations of HDL cholesterol (HDL-C), we conduc ted statistical genetic analyses on data from 526 Mexican American ind ividuals in 25 randomly ascertained pedigrees. By using maximum-likeli hood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, s tandard deviations, relative frequency of a low HDL-C allele, and heri tability for plasma HDL-C levels, plus the effects of sex (genotype sp ecific), age-by-sex, age(2)-by-sex, plasma concentrations of apolipopr otein (apo)AI and triglycerides (genotype specific), exogenous sex hor mone use, and menopausal status under an unrestricted general model. I nclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL -C levels. Of the remaining 21% of the variance, the detected major lo cus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter e stimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P<.05), apoB (P<.01), hepatic lipas e (P<.001), lipoprotein lipase (P<.001), and the LDL receptor (P<.001) . While not excluding the apoE locus (LOD = -0.348, P<.21), the analys is provided no support for tight linkage between it and the detected m ajor locus.