Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis

Background

Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC.

Methods

877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR.

Results

Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was −0.37 and was significantly different than 0 (P = 0.001) and −1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024).

Conclusions

Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC.