The psychological effects of brain-expressed imprinted genes in humans are virtually unknown. Prader-Willi syndrome (PWS) is a neurogenetic condition mediated by genomic imprinting, which involves high rates of psychosis characterized by hallucinations and paranoia, as well as autism. Altered expression of two brain-expressed imprinted genes, MAGEL2 and NDN, mediates a suite of PWS-related phenotypes, including behavior, from studies of mice. We phenotyped a large population of typical individuals for schizophrenia-spectrum and autism-spectrum traits, and genotyped them for the single-nucleotide polymorphism rs850807, which is putatively functional and linked with MAGEL2 and NDN. Genetic variation in rs850807 was strongly and exclusively associated with the Ideas of Reference subscale of the schizophrenia spectrum, which is best typified as paranoia. These findings provide a single-locus genetic model for analyzing the neurological and psychological bases of paranoid thinking, and implicate imprinted genes, and genomic conflicts, in human mentalistic thought.

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