Substantial genetic effects involved in determination of circulating levels of calciotropic hormones in human pedigrees.

Abstract

This paper reports the results of a series of univariate and bivariate statistical genetic analyses that were performed on a sample of nuclear and more complex pedigrees (N = 567 individuals) of an ethnically homogenous White population. Our major objectives were: (1) To quantitatively evaluate the extent and pattern of the putative genetic effects on plasma level variation and covariation of the intact parathyroid hormone (PTH) and 25-hydroxyvitamin D [25(OH)D]; (2) To evaluate the extent of the possible genetic covariation between each of the two calciotropic hormones and two important bone mass traits, namely radiographic hands bone mineral density (BMD) and cortical index (CI). Variance component analysis, as implemented in the statistical package FISHER unambigously demonstrated that in addition to age, genetic factors contribute significantly to interindividual variation of both calciotropic hormones (37.5% for PTH and 53.3% for 25(OH)D). Complex segregation analysis strongly suggested the involvement of major gene effects into the determination of 25(OH)D levels, but was not clear cut with respect to PTH. Significant correlations between circulating levels of study hormones were found (-0.146, P < 0.05 in men and -0.194, P < 0.01 in women). However, no genetic correlation was revealed between PTH and 25(OH)D plasma concentrations. Bivariate analyses showed that familial cross correlations between PTH and BMD and CI measured at the bones of the hand were consistently statistically significant, suggesting moderate, but detectable pleiotropic genetic effects. The corresponding genetic correlations were -0.461 +/- 0.153 and -0.223 +/- 0.113, respectively. Circulating levels of 25(OH)D showed neither phenotypic nor genetic correlation with any of the BMD or CI variation.