This study has several limitations as do all GWAS. In order to increase sample size and study power, we used both community nondiabetic and diabetic subjects with or without nephropathy for gene discovery and replication. Since obesity is a risk factor for diabetes, it is unclear if the presence of diabetes would affect the genetic effect on adiposity measures. T2DM-ESRD subjects in the GWAS may impact nutritional parameters. Indeed, some of the prior GWAS on adiposity also included patients with metabolic disease (e.g., T2DM, coronary artery disease, hypertension) as part of the gene discovery cohorts to increase study power (14,15) and did not show strong heterogeneity of effect size between the healthy subjects and affected patients. In the present study, we selected SNPs for follow-up based on the presence of GWAS association in both nondiabetic and T2DM-ESRD subjects. The overall association signals were comparable in these two groups as shown by the similar observed vs. expected distribution of heterogeneity P values in the respective quantile–quantile plot (Supplementary Figure S3 online). The effect sizes of the five most associated SNPs were
