Additionally, predictive models have yet to include other sources of variation known or hypothesized to influence BMI such as rare variants, gene–gene (G×G) or gene–environment (G×E) interactions, copy number variation, and epigenetic effects. For instance, rare variants which were not included in the current genetic risk profiles are likely to contribute to BMI heritability. For example, in a study by Blakemore et al. (2009), a rare variant in the visfatin gene was associated (p value = 8.0E−5, minor allele frequency 1.6% in control and 0.4% in obese subjects) with reduced risk for obesity. There is also evidence to support the influence of copy number variation (CNV) on BMI. In the Willer et al. (2009) meta-analysis, when examining CNV by SNP-CNV linkage disequilibrium, they found 10-kb and 45-kb deletion polymorphisms upstream of NEGR1 with the 45-kb deletion flanked by their two most associated BMI SNPs. The recent advent of SNP arrays designed for CNV detection may reveal additional genetic associations with BMI. Epigenetic variation, although more widely researched in syndromic obesity such as Prader–Willi, may also be linked to common obesity.
