A genome-wide scan for carotid artery intima-media thickness: The Mexican-American coronary artery disease family study

• Published in: Stroke (1970) 2005-03, Vol.36 (3), p.540-545
• Main Authors: DAI WANG, HUIYING YANG, HSUEH, Willa A, HODIS, Howard N, ROTTER, Jerome I, QUINONES, Manuel J, BULNES-ENRIQUEZ, Isabel, JIMENEZ, Xochitl, DE LA ROSA, Roxana, MODILEVSKY, Tamara, YU, Katherine, YANJIE LI, TAYLOR, Kent D
• Format: Article
• Language: English
• Subjects: Adult; Arteriosclerosis - diagnosis; Arteriosclerosis - genetics; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Biomarkers - analysis; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Arteries - pathology; Chromosome Mapping; Coronary Artery Disease - genetics; Coronary Artery Disease - pathology; Family Health - ethnology; Female; Genetic Linkage - genetics; Genetic Testing - methods; Genome, Human; Genotype; Humans; Insulin Resistance - genetics; Male; Medical sciences; Mexican Americans - genetics; Microsatellite Repeats - genetics; Neurology; Neurosurgery; Quantitative Trait, Heritable; Skull, brain, vascular surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Tunica Intima - pathology; Tunica Media - pathology; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.0000155746.65185.4e

Carotid artery intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with coronary artery disease (CAD), and stroke. CIMT is also an important predictor of clinical cardiovascular events. To systematically identify the genetic determinants of CIMT, we performed a genome-wide scan using data from 91 2-generation Mexican American families ascertained via a parent with CAD diagnosed. CIMT was measured in 274 adult offspring (mean age, 34.6 years) using high-resolution B-mode ultrasound; 413 subjects, including adult offspring and their parents, were genotyped using Marshfield screen set 12 (380 microsatellite markers at approximately 10-cM interval). Heritability was estimated using the variance component approach implemented in SOLAR. Linkage analyses were performed using both the sib-pair regression approach and the variance component approach. The estimated heritability was 0.68, 0.45, and 0.40 for unadjusted, gender- and age-adjusted, and multivariate-adjusted CIMT, respectively. The strongest evidence of linkage was found on chromosome 2 at D2S2944 (logarithm of the odds [LOD]=3.08). Other suggestive linkages were also found on chromosome 6 at D6S1022 to D6S2410 (LOD=2.21) and chromosome 13 at D13S796 to D13S895 (LOD=1.34). These results show that there is a strong genetic effect on CIMT in these Mexican American CAD families. The linkage peak on chromosome 2 suggests that there is a gene (or genes) at this chromosome location influencing CIMT.