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Diabetes 50:614-621, 2001
© 2001 by the American Diabetes Association, Inc.

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

Louis Pérusse1, Treva Rice2, Yvon C. Chagnon1, Jean-Pierre Després3, Simone Lemieux4, Sonia Roy5, Michel Lacaille1, My-Ann Ho-Kim1, Monique Chagnon5, Michael A. Province2, D.C. Rao2, and Claude Bouchard5

1 Physical Activity Sciences Laboratory, Division of Kinesiology, Department of Preventive Medicine, Laval University, Ste-Foy, Québec, Canada
2 Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri
3 Lipid Research Center, CHUQ, CHUL Pavilion and Québec Heart Institute, Laval Hospital, Ste-Foy, Québec, Canada
4 Department of Food Sciences and Nutrition, Faculty of Agricultural and Food Sciences, Laval University, Ste-Foy, Québec, Canada
5 Pennington Biomedical Research Center, Baton Rouge, Louisiana

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 Québec 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 (SIBPAL) and 156 families for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or LOD >=1.75) of multipoint linkage and evidence (P < 0.05) of single-point linkage, 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 others (4q32.1 and 17q21.1) are in the proximity of genes involved in the regulation of food intake. This first genome-wide scan for abdominal fat assessed by computed tomography indicates that there may be several loci determining the propensity to store fat in the abdominal depot and that some of these loci may influence the development of diabetes in obese subjects.

Abbreviations: ASF, abdominal subcutaneous fat; ATF, abdominal total fat; AVF, abdominal visceral fat; CRH, corticotropin-releasing hormone; CT, computed tomography; HSDB3, 3-ß-hydroxy-steroid dehydrogenase; 1GF1, insulin-like growth-factor 1; LOD, logarithm of odds; NHLH2, nescient helix-loop-helix 2; NPY, neuropeptide Y; NPY2R, type 2 NPY receptor; PPARGC1, peroxisome proliferator–activated receptor-{gamma} coactivator 1; PYY, peptide YY; QFS, Québec Family Study; QTL, quantitative trait locus


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