The impact of pedigree structure on heritability estimates for pulse pressure in three studies.
OBJECTIVE
Pulse pressure (PP) is a measure of large artery stiffness and has been shown to be an important predictor of cardiovascular morbidity and mortality. The aims of the present study were to investigate the heritability of PP in three studies, the Diabetes Heart Study (DHS), the Insulin Resistance Atherosclerosis Family Study (IRAS FS), and the NHLBI Family Heart Study (FHS), to estimate the residual heritability after inclusion of a common set of covariates, and to investigate the impact of pedigree structure on estimating heritability.


RESULTS
DHS is primarily a sibling pair nuclear family study design, while both IRAS FS and FHS have large pedigrees. Heritability estimates of log-transformed PP were obtained using variance component models. After adjusting for age, gender, ethnicity/center, height, diabetes status, and mean arterial pressure (MAP), heritability estimates of PP were 0.40 +/- 0.08 , 0.22 +/- 0.05, and 0.19 +/- 0.03 in DHS, IRAS FS, and FHS, respectively. The heritability estimate from DHS was significantly different from both IRAS FS and FHS (both p values <0.05). A random re-sampling technique (modified bootstrap) was used to explore the heritability in the IRAS FS and FHS data when these pedigrees were trimmed to mimic the DHS pedigree structure. The re-sampling method (mimicking a sibling pair nuclear family design in all studies) yielded PP heritability estimates of 0.37, 0.34, and 0.27 in DHS, IRAS FS, and FHS, respectively. There was no significant difference among the heritability estimates from the three studies based on the re-sampling method.


CONCLUSIONS
We have shown that PP has a moderately heritable component in three different studies. These data illustrate the influence of pedigree structure can have on estimating heritability. Thoughtful comparisons of heritability estimates must consider study design factors such as pedigree structure.
Hsu
Fang-Chi
FC
Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. fhsu@wfubmc.edu
Zaccaro
Daniel J
DJ
Lange
Leslie A
LA
Arnett
Donna K
DK
Langefeld
Carl D
CD
Wagenknecht
Lynne E
LE
Herrington
David M
DM
Beck
Stephanie R
SR
Freedman
Barry I
BI
Bowden
Donald W
DW
Rich
Stephen S
SS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005192:Family Health / Q000208:ethnology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010375:Pedigree; D019655:Quantitative Trait, Heritable