Abstract
OBJECTIVE:
To conduct linkage analysis for body mass index (BMI, kg/m2), waist-to-hip ratio (WHR), visceral adipose tissue mass (VAT, cm2) and subcutaneous adipose tissue mass (SAT, cm2) using a whole genome scan.
DESIGN:
Cross-sectional family study.
STUDY SUBJECTS:
African-American families from Los Angeles (AA, n=21 extended pedigrees) and Hispanic-American families (HA) from San Antonio, TX (HA-SA, n=33 extended pedigrees) and San Luis Valley, CO (HA-SLV, n=12 extended pedigrees), totaling 1049 individuals in the Insulin Resistance and Atherosclerosis (IRAS) Family Study.
MEASUREMENTS:
VAT and SAT were measured using a computed tomography scan obtained at the fourth and fifth lumbar vertebrae. All phenotypes were adjusted for age, gender, and study center. VAT, SAT, and WHR were analyzed both unadjusted and adjusted for BMI.
RESULTS:
Significant linkage to BMI was found at D3S2387 (LOD=3.67) in African-Americans, and at D17S1290 in Hispanic-Americans (LOD=2.76). BMI-adjusted WHR was linked to 12q13–21 (D12S297 (LOD=2.67) and D12S1052 (LOD=2.60)) in Hispanic-Americans. The peak LOD score for BMI-adjusted VAT was found at D11S2006 (2.36) in Hispanic families from San Antonio. BMI-adjusted SAT was linked to D5S820 in Hispanic families (LOD=2.64). Evidence supporting linkage of WHR at D11S2006, VAT at D17S1290, and SAT at D1S1609, D3S2387, and D6S1056 was dependent on BMI, such that the LOD scores became nonsignificant after adjustment of these phenotypes for BMI.
CONCLUSIONS:
Our findings both replicate previous linkage regions and suggest novel regions in the genome that may harbor quantitative trait locis contributing to variation in measures of adiposity.
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References
Perusse L, Despres JP, Lemieux S, Rice T, Rao DC, Bouchard C . Familial aggregation of abdominal visceral fat level: results from the Quebec Family Study. Metabolism 1996; 45: 378–382.
Rice T, Despres JP, Daw EW, Gagnon J, Borecki IB, Perusse L, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C . Familial resemblance for abdominal visceral fat: the HERITAGE Family Study. Int J Obes Relat Metab Disord 1997; 21: 1024–1031.
Rice T, Chagnon YC, Perusse L, Borecki IB, Ukkola O, Rankinen T, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Bouchard C, Rao DC . A genomewide linkage scan for abdominal subcutaneous and visceral fat in black and white families. The HERITAGE Family Study. Diabetes 2002; 51: 848–855.
Perusse L, Rice T, Chagnon YC, Despres J-P, Lemieux S, Roy S, Lacaille M, Ho-Kim M-A, Chagnon M, Province MA, Rao DC, Bouchard C . A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec Family Study. Diabetes 2001; 50: 614–621.
Henkin L, Bergman RN, Bowden DW, Ellsworth DL, Haffner SM, Langefeld CD, Mitchell BD, Norris JM, Rewers M, Saad MF, Stamm E, Wagenknecht LE, Rich SS . Genetic epidemiology of insulin resistance and visceral adiposity: The IRAS Family Study design and methods. Ann Epidemiol 2003; 13: 211–217.
Wagenknecht L, Mayer E, Rewers M, Haffner S, Selby J, Borok G, Henkin L, Howard G, Savage PJ, Saad MF, Bergman RN, Hamman R . The Insulin Resistance Atherosclerosis Study (IRAS): Objectives, design, and recruitment results. Ann Epidemiol 1995; 5: 464–472.
Miller RG . Beyond ANOVA. Basics of Applied Statistics. John Wiley and Sons: New York; 1986.
O'Connell JR, Weeks DE . PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 1998; 63: 259–266.
McPeek MS, Sun L . Statistical tests for detection of misspecified relationships by use of genome screen data. Am J Hum Genet 2000; 66: 1076–1094.
Almasy L, Blangero J . Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 1998; 62: 1198–1211.
Goldgar DE . Multipoint analysis of human quantitative genetic variation. Am J Hum Genet 1990; 47: 957–967.
Amos C . Robust variance-components approach for assessing genetic linkage in pedigrees. Am J Hum Genet 1994; 54: 535–543.
Self SG, Liang K-Y . Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under non-standard conditions. J Am Stat Assoc 1987; 82: 605–610.
Blangero J, Williams JT, Almasy L . Robust LOD scores for variance component-based linkage analysis. Genet Epidemiol 2000; 19 (Suppl 1): S8–S14.
Stone S, Abkevich V, Hunt SC, Gutin A, Russell DL, Neff CD, Riley R, Frech GC, Hensel CH, Jammulapati S, Potter J, Sexton D, Tran T, Gibbs D, Iliev D, Gress R, Bloomquist B, Amatruda J, Rae PM, Adams TD, Skolnick MH, Shattuck D . A major predisposition locus for severe obesity, at 4p15–p14. Am J Hum Genet 2002; 70: 1459–1468.
Deng H-W, Deng H, Liu Y-J, Liu Y-Z, Xu FH, Shen H, Conway T, Li J-L, Huang Q-Y, Davies KM, Recker RR . A genomewide linkage scan for quantitative-trait loci for obesity phenotypes. Am J Hum Genet 2002; 70: 1138–1151.
Van der Kallen CJ, Cantor RM, Van Greevenbroek MM, Geurts JM, Bouwman FG, Aouizerat BE, Allayee H, Buurman WA, Lusis AJ, Rotter JI, De Bruin TW . Genome scan for adiposity in Dutch dyslipidemic families reveals novel quantitative trait loci for leptin, body mass index and soluble tumor necrosis factor receptor superfamily 1A. Int J Obes Relat Metab Disord 2000; 24: 1381–1391.
Chagnon YC, Rice T, Perusse L, Borecki IB, Ho-Kim MA, Lacaille M, Pare C, Bouchard L, Gagnon J, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C . Genomic scan for genes affecting body composition before and after training in Caucasians from HERITAGE. J Appl Physiol 2001; 90: 1777–1787.
Mitchell BD, Cole SA, Comuzzie AG, Almasy L, Blangero J, MacCluer JW, Hixson JE . A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor. Diabetes 1999; 48: 1863–1867.
Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, Marks JA, Krakower GR, Jacob HJ, Weber J, Martin L, Blangero J, Comuzzie AG . Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 2000; 97: 14478–14483.
Wu X, RS, Borecki I, Hanis C, Bray M, Lewis CE, Zhu X, Kan D, Luke A, Curb D . A combined analysis of genomewide linkage scans for body mass index, from the National Heart, Lung, and Blood Institute Family Blood Pressure Program. Am J Hum Genet 2002; 70: 1247–1256.
Curtin F, Morabia A, Pichard C, Slosman DO . Body mass index compared to dual-energy x-ray absorptionmetry: evidence for a spectrum bias. J Clin Epidemiol 1997; 50: 837–843.
Smalley KJ, Knerr AN, Kendrick ZV, Colliver JA, Owen OE . Reassessment of body mass indices. Am J Clin Nutr 1990; 52: 405–408.
Borecki IB, Rice T, Bouchard C, Rao DC . Commingling analysis of generalized body mass and composition measures: the Quebec Family Study. Int J Obes Relat Metab 1991; 15: 763–773.
Grays DS, Fujioka K . Use of relative weight and body mass index for the determination of adioposity. J Clin Epidemiol 1991; 44: 545–550.
Taylor RW, Keil D, Godl EJ, Williams SM, Goulding A . Body mass index, waist girth, and waist-to-hip ratio as indexes of total and regional adiposity in women: evaluation using receiver operating characteristic curves. Am J Clin Nutr 1998; 67: 44–49.
Hsueh WC, Mitchell BD, Schneider JL, St Jean PL, Pollin TI, Ehm MG, Wagner MJ, Burns DK, Sakul H, Bell CJ, Shuldiner AR . Genome-wide scan of obesity in the old order Amish. J Clin Endocrinol Metab 2001; 86: 1199–1205.
Chagnon YC, Rankinen T, Snyder EE, Weisnagel SJ, Perusse L, Bouchard C . The Human Obesity Gene Map: The 2002 Update. Obes Res 2003; 11: 313–367.
Muller YL, Bogardus C, Beamer BA, Shuldiner AR, Baier LJ . A functional variant in the peroxisome proliferator-activated receptor γ2 promoter is associated with predictors of obesity and type 2 diabetes in Pima Indians. Diabetes 2003; 52: 1864–1871.
Sun G, Gagnon J, Chagnon Y, Perusse L, Despres JP, Leon AS, Wilmore JH, Skinner JS, Borecki I, Rao DC, Bouchard C . Association and linkage between an insulin-like growth factor-1 gene polymorphism and fat free mass in the HERITAGE Family Study. Int J Obes Relat Metab Disord 1999; 23: 929–935.
Acton S, Osgood D, Donoghue M, Corella D, Pocovi M, Cenarro A, Mozas P, Keilty J, Squazzo S, Woolf EA, Ordovas JM . Association of polymorphisms at the SR-BI gene locus with plasma lipid levels and body mass index in a white population. Arterioscler Thromb Vasc Biol 1999; 19: 1734–1743.
Ye WZ, Reis AF, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G . Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset. Eur J Endocrinol 2001; 145: 181–186.
Hager J, Dina C, Francke S, Dubois S, Houari M, Vatin V, Vaillant E, Lorentz N, Basdevant A, Clement K, Guy-Grand B, Froguel P . A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nat Genet 1998; 20: 304–308.
Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Black AE, Baas D, Takahashi M, Kihara S, Tanaka S, Matsuzawa Y, Blangero J, Cohen D, Kissebah A . The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 2001; 86: 4321–4325.
Bouchard C, Perusse L, Chagnon YC, Warden C, Ricquier D . Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans. Hum Mol Genet 1997; 6: 1887–1889.
Li Y, Bujo H, Takahashi K, Shibasaki M, Zhu Y, Yoshida Y, Otsuka Y, Hashimoto N, Saito Y . Visceral fat: higher responsiveness of fat mass and gene expression to calorie restriction than subcutaneous fat. Exp Biol Med 2003; 228: 1118–1123.
Kanalaey JA, Sames C, Swisher L, Swick AG, Ploutz-Snyder LL, Steppan CM, Sagendorf KS, Feiglin D, Jaynes EB, Meyer RA, Weinstock RS . Abdominal fat distribution in pre- and postmenopausal women: the impact of physical activity, age, and menopausal status. Metabolism 2001; 50: 976–982.
Lynch NA, Nicklas BJ, Berman DM, Dennis KE, Goldberg AP . Reductions in visceral fat during weight loss and walking are associated with improvements in VO2 max. J Appl Physiol 2001; 90: 99–104.
Acknowledgements
We gratefully acknowledge the participating families, and the dedication and work performed by the staff at the clinical sites in San Antonio, Texas, San Luis Valley, Colorado, and Los Angeles; California, laboratory staff at the University of Southern California; and the members of the Coordinating Center at Wake Forest University School of Medicine. This research was supported in part by NIH Grants HL060894 (Bowden), HL060919 (Haffner), HL06091 (Bergman), HL060944 (Wagenknecht), HL061019 (Norris), and HL061210 (Saad).
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Norris, J., Langefeld, C., Scherzinger, A. et al. Quantitative trait loci for abdominal fat and BMI in Hispanic-Americans and African-Americans: the IRAS Family Study. Int J Obes 29, 67–77 (2005). https://doi.org/10.1038/sj.ijo.0802793
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DOI: https://doi.org/10.1038/sj.ijo.0802793
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