Sex differences in genetic and environmental determinants of pulse pressure

Abstract

Pulse pressure (PP) is an independent risk factor for cardiovascular disease. PP rises with age, more so in women. We examined sex differences in the correlations and variance components of PP in adult subjects from 767 nuclear families, enriched with those containing twins, from the Victorian Family Heart Study. After adjusting for age, we found no significant differences in the means or variances of PP in males and females. Under the assumption of no sex differences, the proportions of variance due to shared genes, shared environment, and individual-specific environment were 20%, 23% and 57%, respectively. However, same-sex relative pairs had significantly higher correlations than opposite-sex pairs (P = 0.005), implying the existence of sex-dependent effects. Extensions to the simple variance components model suggested three possible explanations for these differences: smaller genetic correlation between opposite-sex pairs (rhoG,MF = 0.45, P = 0.007); smaller environmental correlation between opposite-sex pairs (P = 0.0003); or different environmental and genetic correlations obtained by estimating genetic, environmental, and individual variance components separately for males and females (not nested, Akaike's Information Criterion (AIC) smaller by 6.69). Under the last model, the genetic component of PP variance is greater for males (1.62 vs 0.33) while the environmental component is greater for females (1.84 vs 0), which would have implications for the planning of gene discovery studies, since heritability would be higher in males. However, the second (environmental) approach best fits the data according to the AIC. Genetic explanations for sex differences in phenotypic correlations may be misleading unless shared environmental factors are also considered. PP illustrates a phenotype in which sex dependency represents an important component of phenotypic determination that can be revealed by detailed variance components modelling.