Pleiotropic effects on cardiovascular risk factors within and between the fourth and sixth decades of life: Implications for genotype × age interactions

We used an approach for detecting genotype × environment interactions to detect and characterize genotype × age interaction in longitudinal measures of three well known cardiovascular risk factors: total plasma cholesterol (TC), systolic blood pressure (SBP), and body weight (Wgt). Our objectives were to determine if the same gene or suite of genes influences quantitative variation in each of these phenotypes in the 4(th )and 6(th )decades of life, to assess the impact of additive gene effects in these two decades, and to evaluate the stability of pleiotropic relationships among these phenotypes. Using the Framingham Heart Study data, we constructed two cross-sectional samples comprising individuals on whom these phenotypes were measured at ages 30-39 years (Original Cohort: exam 1, Offspring Cohort: exam 2) and at ages 50-59 years (Original Cohort: exam 11, Offspring Cohort: exam 5). We also constructed a longitudinal sample from the cross-sectional sample members for whom measures on these traits were available at both ages (i.e., 4(th )and 6(th )decades of life). Patterns of pleiotropy, inferred from genetic correlations between traits, differ between the two age classes. Further, additive genetic variance in SBP during the 4(th )decade of life is attributable to a different gene or suite of genes than during the 6(th). The magnitude of the effect increases for SBP. Variation in TC and Wgt appear to be influenced by the same gene or genes in both decades. The magnitude of the effect is stable for TC, but increases dramatically with age for Wgt.