One can investigate the genetic homogeneity of items or symptoms underlying a sum-score or a case–control status by studying the genetics of the individual items. If items prove to be genetically heterogeneous, identification of more homogeneous subsets or clusters of items may be expedient to optimize the statistical power to disentangle genetic determinants. Indeed, detection of local variants, affecting, e.g., only one cluster of items but not others, might facilitate biological understanding.
