Intrafamilial aggregation and heritability of office-day blood pressure difference in a community of African ancestry: implications for genetic association studies.

Abstract

An inability to show consistent relationships between gene variants and blood pressure (BP) may be confounded by the use of office BP measurement. Whether the difference between office BP and day BP (office-day) is genetically predetermined is unknown. We therefore aimed to determine the intrafamilial aggregation and heritability of office-day BP. Nurse-derived office BP (mean of 5 measurements according to guidelines) and 24-h ambulatory BP were determined for 592 participants from 198 families (67 spouse pairs, 361 parent-child pairs, and 169 sibling-sibling pairs), with 12 families having three generations, from an urban developing community of black Africans. Heritability estimates were determined using SAGE software. With adjustments for confounders, office systolic BP (SBP) (h=0.35±0.09, P<0.0001) showed comparable heritability estimates to 24-h SBP (h=0.33±0.09, P<0.0001). Similarly, with adjustments for confounders, office diastolic BP (DBP) (h=0.37±0.09, P<0.0001) showed comparable heritability estimates as 24-h DBP (h=0.35±0.09, P<0.0001). However, multivariate adjusted heritability estimates of day SBP (h=0.29±0.09, P<0.0001) and DBP (h=0.33±0.09, P<0.0001) were not diminished by further adjustments for office SBP (h=0.42±0.09, P<0.0001) or DBP (h=0.34±0.09, P<0.0001). Further, independent of confounders, office-day BP showed significant intrafamilial aggregation and heritability (SBP: h=0.51±0.10, P<0.0001; DBP: h=0.37±0.09, P<0.0001), effects that persisted with further adjustments for office, day, or day-night BP (P<0.0005 for SBP and DBP). Although office and ambulatory BP may show similar heritability estimates, genetic associations with carefully determined office BP measurements may be confounded by the heritability of office-day BP differences.