information about gene-to-phenotype relations. Alignment of phenotype associations across both humans and mice, however, adds validity to both. Very large, densely genotyped or sequenced populations will be needed to more deeply interrogate the human phenome. The third problem is linkage disequilibrium. The intervals in which sequence variants are located is a critical factor in mapping its phenotype spectrum. Pleiotropy will be inflated as a function of gene density, SNP density, and haplotype block structure. Deconvolving contributions of linked polymorphisms will, in most cases, still require independent experimental validation and, when possible, PheWAS of human cohorts.
