A genetic study of hypoalphalipoproteinemia

Complex segregation analysis under the unified mixed model of inheritance (major gene and multifactorial) is performed on families ascertained through 23 probands with hypoalphalipoproteinemia (depressed HDL-cholesterol, denoted HDL-c). Evidence for segregation of a recessive major gene for depressed HDL-c with frequency q = 0.116, in addition to multifactorial transmission (H = 0.572), is found in these families. Reanalysis of a subset of families with severely depressed HDL-c confirms the conclusions based on the original analysis, except that different definitions of "affection" give rise to different estimates of gene frequency. Our finding of a recessive mode of inheritance differs from previous claims for a dominant gene because previous analyses did not use a mixed model for segregation analysis of hypoalphalipoproteinemia. When the significant multifactorial background is neglected, we also find evidence for the invalid claim of a dominant gene. This demonstrates the necessity of using mixed models for determining the mode of inheritance of a given phenotype.