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

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.