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  • Title: Genome-wide scan for adiposity-related phenotypes in adults from American Samoa.
    Author: Dai F, Keighley ED, Sun G, Indugula SR, Roberts ST, Aberg K, Smelser D, Tuitele J, Jin L, Deka R, Weeks DE, McGarvey ST.
    Journal: Int J Obes (Lond); 2007 Dec; 31(12):1832-42. PubMed ID: 17621312.
    Abstract:
    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 cM 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.
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