Complex Segregation Analysis of Plasma Lipid and Lipoprotein Variables in a Jerusalem Sample of Nuclear Families

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Abstract
Plasma lipid and lipoprotein concentrations from 3,074 nuclear families in the multiethnic Jerusalem Lipid Research Clinic study population were analyzed for possible involvement of major genes in determination of high levels of these traits. Complex segregation analysis under a mixed model including major gene and multifactorial transmissible components was performed on transformed-plasma lipids and lipo-proteins after covariance adjustment for age, sex and environmental measures. Likelihood analysis provided evidence for recessive major genes influencing plasma triglyceride, and low-density lipoprotein cholesterol (LDL-C). The estimated gene frequencies for triglyceride and for hyperbetalipoproteinemia in our study population were about 0.1. Our positive results for total cholesterol and high-density lipoprotein cholesterol (HDL-C) were nonconclusive and the major effects could result from causes other than major genes. The mixed-model parameters were homogeneous across origin groups for LDL-C and HDL-C and heterogeneous for total plasma cholesterol and triglyceride. The multifactorial-transmission heritability index was similar in all origin groups for all the traits. The origin heterogeneity in the major gene parameters appeared to be mainly due to the North African group which favored a multifactorial transmission for all traits except for LDL-C.