The Collaborative Lipid Research Clinics Program Family Study: detection of major genes influencing lipid levels by examination of heterogeneity of familial variances.

Age, sex-adjusted, and transformed lipid and lipoprotein data on over 1,200 white North American sibships in the Collaborative Lipid Research Clinics Family Study were analyzed for possible major genes causing high or low levels of these traits. The sibships were stratified on the basis of parents' trait values, and within-sibship variance in the high (or low) families was compared to that in the normal families via an F-test. The null hypothesis of multifactorial transmission was strongly rejected for low LDL, low total cholesterol, and high HDL families. An analysis of spouse-pair variance gave similar results. This may reflect the presence of dominant genes for hyperalpha- and hypobetalipoproteinemia. There was weaker evidence for single genes causing hyperbetalipoproteinemia. There was no evidence for major genes influencing triglyceride levels. Methodological issues with significant bearing on these results and those of other studies are discussed.