Background and Purpose -Ultrasound examination of the carotid arteries yiel ds several quantitative measures that may serve as intermediate phenotypes in ge netic studies. This study was undertaken to compare the heri...Background and Purpose -Ultrasound examination of the carotid arteries yiel ds several quantitative measures that may serve as intermediate phenotypes in ge netic studies. This study was undertaken to compare the heritabilities of 3 ultr asound measures: intima-media thickness (IMT), plaque score, and maximal steno sis. Methods -We studied 565 individuals from 154 families ascertained by an a ffected parent with carotid artery atherosclerosis. IMT, plaque score, and maxim al stenosis of the carotid arteries were examined by B-mode ultrasound and ana lyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage ana lysis routines). Covariates were age, sex, weight, height, body mass index (BMI) , arterial hypertension, diabetes mellitus, amount of nicotine consumed, and pla sma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HD L) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VII I, factor XIII, fibrinogen, and von Willebrand factor (vWF). Results -After ac counting 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 p laque score was influenced by age, sex, hypertension, diabetes mellitus, hyperch olesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these wer e considered, no significant heritability could be detected. Heritability of ste nosis was estimated as h2=0.47± 0.07 (P=0.006), with age, sex, BMI, hypertensio n, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariat es. Conclusions -Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than tho se influencing known risk factors. This makes MT a promising candidate for use a s an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.展开更多
文摘Background and Purpose -Ultrasound examination of the carotid arteries yiel ds several quantitative measures that may serve as intermediate phenotypes in ge netic studies. This study was undertaken to compare the heritabilities of 3 ultr asound measures: intima-media thickness (IMT), plaque score, and maximal steno sis. Methods -We studied 565 individuals from 154 families ascertained by an a ffected parent with carotid artery atherosclerosis. IMT, plaque score, and maxim al stenosis of the carotid arteries were examined by B-mode ultrasound and ana lyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage ana lysis routines). Covariates were age, sex, weight, height, body mass index (BMI) , arterial hypertension, diabetes mellitus, amount of nicotine consumed, and pla sma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HD L) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VII I, factor XIII, fibrinogen, and von Willebrand factor (vWF). Results -After ac counting 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 p laque score was influenced by age, sex, hypertension, diabetes mellitus, hyperch olesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these wer e considered, no significant heritability could be detected. Heritability of ste nosis was estimated as h2=0.47± 0.07 (P=0.006), with age, sex, BMI, hypertensio n, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariat es. Conclusions -Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than tho se influencing known risk factors. This makes MT a promising candidate for use a s an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.
