Heritability of carotid artery atherosclerotic lesions: an ultrasound study in 154 families.
OBJECTIVE
Ultrasound examination of the carotid arteries yields several quantitative measures that may serve as intermediate phenotypes in genetic studies. This study was undertaken to compare the heritabilities of 3 ultrasound measures: intima-media thickness (IMT), plaque score, and maximal stenosis.


METHODS
We studied 565 individuals from 154 families ascertained by an affected parent with carotid artery atherosclerosis. IMT, plaque score, and maximal stenosis of the carotid arteries were examined by B-mode ultrasound and analyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage analysis routines). Covariates were age, sex, weight, height, body mass index (BMI), arterial hypertension, diabetes mellitus, amount of nicotine consumed, and plasma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VIII, factor XIII, fibrinogen, and von Willebrand factor (vWF).


RESULTS
After accounting for the covariables age, sex, hypertension, diabetes mellitus, and Lp(a), heritability of IMT was estimated as h2=0.61+/-0.17 (P=0.001). Variation of plaque score was influenced by age, sex, hypertension, diabetes mellitus, hypercholesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these were considered, no significant heritability could be detected. Heritability of stenosis was estimated as h2=0.47+/-0.07 (P=0.006), with age, sex, BMI, hypertension, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariates.


CONCLUSIONS
Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than those influencing known risk factors. This makes IMT a promising candidate for use as an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.
Moskau
Susanna
S
Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
Golla
Astrid
A
Grothe
Christoph
C
Boes
Monika
M
Pohl
Christoph
C
Klockgether
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D016893:Carotid Stenosis / Q000000981:diagnostic imaging* / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography