A re-examination of major locus hypotheses for high density lipoprotein cholesterol level using 2,170 persons screened in 55 Utah pedigrees.

A dominant major locus (allele frequency of .0025 +/- .0014), resulting in low levels of high density lipoprotein cholesterol (HDL-C), was revealed by likelihood analysis on 2,170 persons in 55 Utah pedigrees. This allele was expressed through HDL-C levels ranging from 20 to 30 mg/dl in seven persons in two pedigrees. Early coronary heart disease was associated with the allele in one pedigree, but not in the other. In the pedigree without associated heart disease, HDL subfractions HDL2 and HDL3 were both low in individuals with the low HDL-C allele. No other major locus determining either high or low levels of HDL-C was identified in our sample. Polygenic heritability as part of the mixed model was estimated as .561 +/- .035.