impact on impairment, and their underlying biology. In the context of gene-finding studies, power to detect associated variants is potentially lost when the summed items or symptoms are biologically heterogeneous. Specifically, the use of composite scores in gene-finding studies directs the focus of analysis to those variants that affect the majority of aggregated items, i.e., ‘global variants’. The genetic signal of “local” variants, affecting only one or a few of the aggregated items, is severely diluted10. That is, if summed items or symptoms are genetically heterogeneous, then GWAS analysis of their sum may yield a mix of diluted signals, which will bear resemblance to the infinitesimal model.
