Despite the differences between datasets, we identified ten genes on non-HSA21 chromosomes that were dysregulated all studies: GRIK3, NFE2L2, SEMA5B, POU6F2, HECW1, BDNF, ARL4D, JUND, COMT, and PRKX. As these ten genes are consistently dysregulated across age, sex, sample type, and sequencing technology, they may strongly impact the consistent neurodevelopmental phenotypes in DS leading to the intellectual disability. The gene discussed is COMT; the disease is Intellectual disability.