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

A Genome-Wide Scan for Abdominal Fat Assessed by Computed Tomography in the Québec Family Study Louis Pérusse 1 , Treva Rice 2 , Yvon C. Chagnon 1 , Jean-Pierre Després 3 , Simone Lemieux 4 , Sonia Roy 5 , Michel Lacaille 1 , My-Ann Ho-Kim 1 , Monique Chagnon 5 , Michael A. Province 2 , D.C. Rao 2 and Claude Bouchard 5 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 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 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 oth