'The missing genes: what happened to the heritability of psychiatric disorders?'

Less than 2% of the 80-90% heritability of major psychiatric disease, for example, schizophrenia and manic-depressive illness is attributable to genes identified by linkage and association. Where is the missing heritability? The recently described PRDM9 gene imposes epigenetic stability on the XY body in male meiosis including Sapiens-specific variation relating to a gene pair (Protocadherin11XY) created by X to Y duplication at 6MYA. Thus sexually dimorphic variation that distinguishes the species may be transmitted between generations in epigenetic form that evades detection by linkage and association. Molecular Psychiatry (2011) 16, 362-364; doi:10.1038/mp.2010.92