Genetic effects on obesity assessed by bivariate genome scan: the Mexican-American coronary artery disease study.
OBJECTIVE
To identify the genetic determinants of obesity using univariate and bivariate models in a genome scan.


METHODS
We evaluated the genetic and environmental effects and performed a genome-wide linkage analysis of obesity-related traits in 478 subjects from 105 Mexican-American nuclear families ascertained through a proband with documented coronary artery disease. The available obesity traits include BMI, body surface area (BSA), waist-to-hip ratio (WHR), and trunk fat mass as percentage of body weight. Heritability estimates and multipoint linkage analysis were performed using a variance components procedure implemented in SOLAR software.


RESULTS
The heritability estimates were 0.62 for BMI, 0.73 for BSA, 0.40 for WHR, and 0.38 for trunk fat mass as percentage of body weight. Using a bivariate genetic model, we observed significant genetic correlations between BMI and other obesity-related traits (all p < 0.01). Evidence for univariate linkage was observed at 252 to approximately 267 cM on chromosome 2 for three obesity-related traits (except for WHR) and at 163 to approximately 167 cM on chromosome 5 for BMI and BSA, with the maximum logarithm of the odds ratio score of 3.12 (empirical p value, 0.002) for BSA on chromosome 2. Use of the bivariate linkage model yielded an additional peak (logarithm of the odds ratio = 3.25, empirical p value, 0.002) at 25 cM on chromosome 7 for the pair of BMI and BSA.


CONCLUSIONS
The evidence for linkage on chromosomes 2q36-37 and 5q36 is supported both by univariate and bivariate analysis, and an additional linkage peak at 7p15 was identified by the bivariate model. This suggests that use of the bivariate model provides additional information to identify linkage of genes responsible for obesity-related traits.
Li
Xiaohui
X
Genetic Epidemiology, Medical Genetic Institute, Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Quiñones
Manuel J
MJ
Wang
Dai
D
Bulnes-Enriquez
Isabel
I
Jimenez
Xochitl
X
De La Rosa
Roxana
R
Aurea
George L
GL
Taylor
Kent D
KD
Hsueh
Willa A
WA
Rotter
Jerome I
JI
Yang
Huiying
H
D000328:Adult; D000704:Analysis of Variance; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D018895:Microsatellite Repeats; D009765:Obesity / Q000235:genetics*; D049629:Waist-Hip Ratio
D005819:Genetic Markers