A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec Family Study

To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat wa s performed in the Quebec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assesse d from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abd ominal subcutaneous fat (ASF) was obtained by computing the difference betw een 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) mea sured by underwater weighing, and the adjusted phenotypes were used in link age analyses. A total of 293 microsatellite markers spanning the 22 autosom al chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point (SIBPAL) and 156 f amilies for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marke r D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S10 45) located within 2 cM of D12S2078 also provided evidence of sib-pair link age with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regi ons with highly suggestive evidence (P < 0.0023 or LOD <greater than or equ al to>1.75) of multipoint linkage and evidence (P < 0.05) of single-point l inkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23 , and 17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes involved in the regulation of sex steroid levels, whereas two othe rs (4q32.1 and 17q21.1) are in the proximity of genes involved in the regul ation of food intake. This first genome-wide scan for abdominal fat assesse d by computed tomography indicates that there may be several loci determini ng the propensity to store fat in the abdominal depot and that some of thes e loci may influence the development of diabetes in obese subjects.