Susceptibility loci for adiposity phenotypes on 8p, 9p, and 16q in American Samoa and Samoa

Abstract

Obesity is a complex phenotype affected by genetic and environmental influences such as sociocultural factors and individual behaviors. Previously, we performed two separate genome-wide investigations for adiposity-related traits (BMI, percentage body fat (%BF), abdominal circumference (ABDCIR), and serum leptin and serum adiponectin levels) in families from American Samoa and in families from Samoa. The two polities have a common evolutionary history but have lately been influenced by variations in economic development, leading to differences in income and wealth and in dietary and physical activity patterns. We now present a genome-wide linkage scan of the combined samples from the two polities. We adjust for environmental covariates, including polity of residence, education, cigarette smoking, and farm work, and use variance component methods to calculate univariate and bivariate multipoint lod scores. We identified a region on 9p22 with genome-wide significant linkage for the bivariate phenotypes ABDCIR-%BF (1-d.f. lod 3.30) and BMI-%BF (1-d.f. lod 3.31) and two regions with genome-wide suggestive linkage on 8p12 and 16q23 for adiponectin (lod 2.74) and the bivariate phenotype leptin-ABDCIR (1-d.f. lod 3.17), respectively. These three regions have previously been reported to be linked to adiposity-related phenotypes in independent studies. However, the differences in results between this study and our previous polity-specific studies suggest that environmental effects are of different importance in the samples. These results strongly encourage further genetic studies of adiposity-related phenotypes where extended sets of carefully measured environmental factors are taken into account.

Figure 1

Multipoint linkage results from chromosomes 9 (left column) and 16 (right column). The top row shows univariate linkage when adjusted for the basic covariate set. The middle row shows univariate linkage results when the environmental set was screened for. The bottom row shows bivariate multipoint lod scores. Genome-wide significance (lod 3.3) is indicated by the horizontal dashed line, and suggestive linkage is indicated by the horizontal solid line (lod 1.9). The locations of potential candidate genes, JAK2 and AGRP, are indicated with asterisks.

Figure 2

Multipoint linkage results from chromosome 8 when the extended covariate set was screened for. Suggestive linkage is indicated by the horizontal line (lod 1.9). The location of the potential candidate gene, ADRB3, is indicated with an asterisk.