Pilot studies of the genetics of obesity in the western Alaska Native population

Abstract

Obesity in Alaska Natives is increasing, posing significant health risk for the development of associated diseases. This study examined candidate obesity genes in a set of anonymized Alaska Native DNA samples for loci that might predict obesity risk. DNA samples were divided into three groups according to body mass index: lean (BMI <̲23), in-between (23<BMI <30), and obese (BMI>̲ 30). Screening of 5,043 base pairs from the exons of leptin (LEP), leptin receptor (LEPR), neuropeptide-y (NPY), and melanocortin-4-receptor (MC4R) yielded previously discovered SNPs in NPY and LEPR. Additionally, two known promoter region SNPs in NPY and Uncoupling Protein-2 (UCP2) were analyzed. SNPs were in Hardy Weinberg equilibrium, showed little genetic variation between populations, and were not associated with BMI category. We concluded that the study lacked power to detect an association due to an inability to correct for variables known to affect BMI and a small sample size. However, this study enabled pilot studies of several SNP genotyping platforms and the evaluation of allele frequencies in the Alaska Native population, illuminating the value of known SNP genotyping vs. SNP discovery and the benefit of a direct association study vs. an indirect association study.