NOS3 and obesity due to melanocortin 4 receptor deficiency: Assuming the interaction between a common NOS3 sequence variant and obesity reported here is only a single occurrence of a more general phenomenon, large well-powered studies carried out in populations where phenotypic heterogeneity has been minimized may be required to bridge the gap between the substantial heritability estimated for many complex disorders and the proportion of interindividual variation thus far accounted for by common sequence differences.