Shared and unique genetic effects among seven HDL phenotypes.
The purpose of this study was to investigate the genetic control of various HDL measures and to determine the proportion of genetic variance explained by shared genes (ie, pleiotropy) and the proportion unique to each trait. The data used were drawn from large, randomly ascertained pedigrees of Mexican Americans participating in the San Antonio Family Heart Study. Data were available for 655 individuals (258 men and 397 women) in 26 families. We performed a multivariate quantitative genetic analysis to simultaneously estimate both the additive genetic and random environmental correlations among seven HDL phenotypes. These seven HDL phenotypes can be divided into two categories: measures of concentration and estimates of particle size. Concentration was measured for apo A-I, apo A-II, esterified cholesterol, and unesterified cholesterol, and particle size was estimated for apo A-I, apo A-II, and esterified cholesterol. The heritabilities (h2) for each of the seven traits were significantly greater than zero (P<.05) and ranged from 0.2 to 0.6. When considered in a pairwise fashion, all combinations of these traits showed marked genetic correlations (rho(G)=0.33 to 0.87) and all were significantly greater than zero (P<.05), indicative of pleiotropic effects. However, we found substantial unique genetic variance for each of these traits even after accounting for the effects shared in common with all the remaining measures. We conclude that the genetic variation in these HDL phenotypes is a result of the action of common as well as unique genes.
Comuzzie
A G
AG
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Tex 78245-0549, USA. agcom@darwin.sfbr.org
Rainwater
D L
DL
Blangero
J
J
Mahaney
M C
MC
VandeBerg
J L
JL
MacCluer
J W
JW
D000328:Adult; D016632:Apolipoprotein A-I / Q000032:analysis; D016633:Apolipoprotein A-II / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000208:ethnology; D010316:Particle Size; D010641:Phenotype
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D002784:Cholesterol