title: Methylomic profiling of human brain tissue  supports a neurodevelopmental origin for  schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances ine arly brain development. There is mounting evidence to support a role for developmentally regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development.
  
  
  RESULTS
  We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci,particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples.Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that schizophrenia-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development.
  
  
  CONCLUSIONS
  Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects.
authors.affiliation: Institute of Psychiatry, King’s College London, London, SE5 8AF, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pidsley
authors.forename: Joana
authors.initials: J
authors.lastname: Viana
authors.forename: Eilis
authors.initials: E
authors.lastname: Hannon
authors.forename: Helen
authors.initials: H
authors.lastname: Spiers
authors.forename: Claire
authors.initials: C
authors.lastname: Troakes
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Saraj
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Bray
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
mesh_terms: D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D047109:Fetal Development / Q000235:genetics*; D006801:Humans; D017397:Prefrontal Cortex / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism