A genome-wide scan for carotid artery intima-media thickness: the Mexican-American Coronary Artery Disease family study.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Wang
Dai
D
Medical Genetics Institute, Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, 8700 Beverly Blvd, SSB 378, Los Angeles, Calif 90048, USA. dai.wang@cshs.org
Yang
Huiying
H
Quiñones
Manuel J
MJ
Bulnes-Enriquez
Isabel
I
Jimenez
Xochitl
X
De La Rosa
Roxana
R
Modilevsky
Tamara
T
Yu
Katherine
K
Li
Yanjie
Y
Taylor
Kent D
KD
Hsueh
Willa A
WA
Hodis
Howard N
HN
Rotter
Jerome I
JI
D000328:Adult; D001161:Arteriosclerosis / Q000175:diagnosis / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000473:pathology*; D002874:Chromosome Mapping; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology*; D005192:Family Health / Q000208:ethnology*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D019655:Quantitative Trait, Heritable; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology*
D015415:Biomarkers