Hypertension and sodium-lithium countertransport in Utah pedigrees: evidence for major-locus inheritance

Likelihood analysis was used to test for evidence that an allele at a major locus elevates rates of sodium-lithium countertransport (SLC) in a sample of 1,989 members of 89 Utah pedigrees. The pedigrees were ascertained through two or three sibs who died of stroke before age 74 years (stroke pedigrees), through hypertensive and normotensive probands of the Salt Lake Center of the Hypertension Detection and Followup Program (HDFP pedigrees), or through men who suffered a myocardial infarction before age 55 years (coronary pedigrees). Major-locus inheritance could be rejected in the total sample; transmission probability estimates of tau1 = .972, tau2 = .520, tau3 = .185 differed significantly from Mendelian transmission specified by tau1 = 1, tau2 = 1/2, tau3 = 0. However, heterogeneity between ascertainment groups was significant (chi2(18) = 40.06, P less than .01) and justified analysis within subsets of the sample. In the stroke pedigrees, evidence of major-locus inheritance was not found; polygenic heritability was estimated as .647. In the HDFP pedigrees, estimates of tau1 = .987, tau2 = .430, tau3 = .506 differed significantly from Mendelian transmission; the inferred model consisted of a mixture of two distributions incompatible with both Mendelian and environmental transmission but compatible with polygenic inheritance within distributions. In the coronary pedigrees, the hypothesis of Mendelian transmission could not be rejected. In the coronary pedigrees, the evidence supported an incompletely recessive allele with a frequency of .227 which elevated the level of SLC to a mean of .530 mmol/liter RBC/h.(ABSTRACT TRUNCATED AT 250 WORDS)