A Genome-Wide Scan for Abdominal Fat Assessed by Computed Tomography in the Québec Family Study

Abstract

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...

Sex-specific findings from a genome-wide linkage analysis of human fatness in non-Hispanic whites and African Americans: The HyperGEN Study

“…In our study, the marker that demonstrated the strongest evidence for linkage coincides with a region reported by Perusse et al, 67 Genome scan of body fatness: HyperGEN CE Lewis et al subcutaneous fat in participants of the Quebec Family Study (Table 5). Two plausible candidate genes are located in the 17 cM (1 LOD unit drop) support interval, scavenger receptor type B class 1 (SRB1) and acetyl-CoA carboxylase-beta (ACACB).…”

Genetic mapping of a 17q chromosomal region linked to obesity phenotypes in the IRAS family study

“…Only two additional studies have conducted linkage analyses for such sophisticated measurements of adiposity, one in a French Caucasian population and one in an African-American and Caucasian population, 28,29 To our knowledge, no linkage studies in Hispanic populations have been carried out using CT measures of obesity. Thus, the IRASFS contributes novel data on linkage for specific fat depots in a Hispanic cohort.…”

“…29 Linkage was identified with markers D17S2180 (67cM), D17S1290 (82cM), and D17S1301 (100 cM), all with a LOD ¼ 2.2. 29 D17S1290 and D17S1301 were also genotyped in the IRASFS, with LOD scores for VAT ¼ 0.53 and 2.84, respectively, and LOD scores for BMI ¼ 1.01 and 2.11, respectively.…”

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

“…There is suggestive evidence of linkage of abdominal subcutaneous fat to the chromosomal region 17q21.1 (LOD= 2.24), which is in close proximity to where both the PYY and PPY genes are located [26].…”