To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat was performed in the Qué bec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal subcutaneous fat (ASF) was obtained by computing the difference between ATF and AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well as for total amount of body fat (kilogram of fat mass) measured by underwater weighing, and the adjusted phenotypes were used in linkage analyses. A total of 293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point ( A n elevated body fat content, as commonly seen in overweight or obese individuals, and particularly excess abdominal fat (1) are recognized as risk factors for type 2 diabetes and cardiovascular disease. The evidence suggesting that the amount of abdominal visceral fat is influenced by genetic factors has been recently reviewed (2). Two family studies have provided heritability estimates for abdominal total fat (ATF), abdominal subcutaneous fat (ASF), and abdominal visceral fat (AVF) areas measured by computed tomography (CT). In the first study based on 366 adult subjects from the Qué bec Family Study (QFS), age-and sexadjusted heritability estimates of 70, 68, and 68% were obtained for ATF, ASF, and AVF, respectively (3). After adjustment for fat mass measured by hydrodensitometry, heritability estimates were slightly reduced for ASF (42%) and AVF (56%). For ATF, there were sex differences in the heritabilities with higher values in male (76%) than in female (69%) and cross-sex (57%) pairs. In the second study based on 483 subjects from the HERITAGE Family Study, heritability estimates of 47 and 48% were obtained for AVF before and after adjustment for fat mass, respectively (4). Segregation analyses of these two study samples have also provided tentative evidence for the role of a single gene with a major effect on AVF (5,6). The results of these family studies indicate that the amount of fat stored in the abdomen, independent of overall body fatness, is strongly influenced by genetic factors.Despite evidence of a strong genetic component determining the amount of abdominal fat, very little is known about the nature of the genes involved. Only a few candidate genes, including the glucocorticoid receptor gene (7), the  3 -adrenergic receptor gene (8,9), and the fatty acid binding protein 2 gene (10), were found to be associated with abdominal fat. The identification of genes associated with complex phenotypes such as abdominal fat is limited when based on the candidate gene approach only. A genome-wide scan allows the identification of chromosomal regions that may harbor novel genes affecting a phenotype. Here we report the results of the f...
An autosomal genomewide search for genes related to body composition and its changes after a 20-wk endurance-exercise training program has been completed in the HERITAGE Family Study. Phenotypes included body mass index (BMI), sum of eight skinfold thicknesses, fat mass (FM), fat-free mass, percent body fat (%Fat), and plasma leptin levels. A maximum of 364 sib-pairs from 99 Caucasian families was studied with the use of 344 markers with single-point and multipoint linkage analyses. Evidence of significant linkage was observed for changes in fat-free mass with the S100A and the insulin-like growth factor I genes (P = 0.0001). Suggestive evidence (2.0 < or = Lod < 3.0; 0.0001 < P < or = 0.001) was also observed for the changes in FM and %Fat at 1q31 and 18q21-q23, in %Fat with the uncoupling protein 2 and 3 genes, and in BMI at 5q14-q21. At baseline, suggestive evidence was observed for BMI at 8q23-q24, 10p15, and 14q11; for FM at 14q11; and for plasma leptin levels with the low-density lipoprotein receptor gene. This is the first genomic scan on genes involved in exercise-training-induced changes in body composition that could provide information on the determinants of weight loss.
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