These DMROIs were associated with genes which have been previously linked to cognitive development or function such as TCF4 (transcription factor 4), a bHLH transcription factor deleted in Pitt-Hopkins syndrome34 where individuals exhibit severe motor dysfunction and mental retardation; IL1RN (interleukin 1 receptor antagonist) and MMP3 (matrix metallopeptidase 3), where SNPs associated with these genes have been linked to cognitive decline;35,36 and NFE2L2 (nuclear factor erythroid 2-like 2) which is known to be decreased in the brain during oxidative stress.37 The gene discussed is IL1RN; the disease is Mental deterioration.