Whereas reported single marker associations account for only a limited fraction of trait variance, linear mixed model approaches simultaneously consider the effects of common variation across the entire genome. As applied to BMI, this approach has demonstrated that common SNPs account for up to 17% of the phenotypic variance in BMI [15]. However, given that reported heritability estimates for BMI are typically much higher (40-70% [6]), a substantial proportion of the variance remains unaccounted for. To what extent this “missing heritability” is attributable to rare or structural variation is increasingly of interest to researchers and supported by a growing list of rare copy number variants (CNV) reported to be associated with BMI and obesity [16–24].
