Genome-wide scan for adiposity-related phenotypes in adults from American Samoa

• Published in: International Journal of Obesity 2007-12, Vol.31 (12), p.1832-1842
• Main Authors: Dai, F, Keighley, E D, Sun, G, Indugula, S R, Roberts, S T, Åberg, K, Smelser, D, Tuitele, J, Jin, L, Deka, R, Weeks, D E, McGarvey, S T
• Format: Article
• Language: English
• Subjects: Adipose tissues; Adiposity - ethnology; Adiposity - genetics; Adult; Adults; American Samoa; Biological and medical sciences; Body fat; Body Mass Index; Chromosome Mapping; Cigarettes; Diabetes; Education; Epidemiology; Families & family life; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene mapping; Genes; Genetic aspects; Genetic Linkage - genetics; Genome, Human; Genomes; Genomics; Health aspects; Health Promotion and Disease Prevention; Humans; Internal Medicine; Leptin; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Modernization; Obesity; Obesity - ethnology; Obesity - genetics; original-article; Overweight; Pedigree; Phenotype; Properties; Public Health; Quantitative Trait Loci; Review boards; Risk factors; Skinfold Thickness; Statistics as Topic; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Women
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803675

Objective: To detect quantitative trait loci influencing adiposity-related phenotypes assessed by body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT) and fasting serum leptin and adiponectin using a whole genome linkage scan of families from American Samoa. Design: Family-based linkage analysis, the probands and family members were unselected for obesity. Subjects: A total of 583 phenotyped American Samoan adults, of which 578 were genotyped in 34 pedigrees. Measurements: A total of 377 autosomal and 18 X chromosome microsatellite markers were typed at an approximate average spacing of 10 c M spanning the genome. Multipoint LOD (logarithm of the odds) scores were calculated using variance-components approaches and SOLAR/LOKI software. The covariates simultaneously evaluated were age, sex, education, farm work and cigarette smoking, with a significance level of 0.1. Due to the stochastic nature of LOKI, we report the average of maximum LOD scores from 10 runs. Results: Significant linkage to leptin was found at 6q32.2 with LOD of 3.83. Suggestive linkage to leptin was found at 16q21:LOD=2.98, 1q42.2:LOD=1.97, 5q11.2:LOD=2.08, 12q24.23:LOD=2.00, 19p13.3:LOD=2.05; adiponectin was linked to 13q33.1–q22.1:LOD=2.41; %BFAT was linked to 16q12.2–q21, LOD=2.24; ABDCIR was linked to 16q23.1:LOD=1.95; %BFAT-adjusted leptin to 14q12, LOD=2.01; %BFAT-adjusted ABDCIR to 1q31.1, LOD=2.36, to 3q27.3–q28, LOD=2.10 and to 12p12.3, LOD=2.04. Conclusion: We found strong evidence for a major locus on 6q23.2 influencing serum leptin levels in American Samoans. The 16q21 region appears to harbor a susceptibility locus that has significant pleiotrophic effects on phenotypes BMI, %BFAT, leptin and ABDCIR as shown by bivariate linkage analyses. Several other loci of varying significance were detected across the genome.