title: Understanding the genetic liability to schizophrenia through the neuroepigenome.
abstract: The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) recently identified 108 loci associated with increased risk for schizophrenia (SCZ). The vast majority of these variants reside within non-coding sequences of the genome and are predicted to exert their effects by affecting the mechanism of action of cis regulatory elements (CREs), such as promoters and enhancers. Although a number of large-scale collaborative efforts (e.g. ENCODE) have achieved a comprehensive mapping of CREs in human cell lines or tissue homogenates, it is becoming increasingly evident that many risk-associated variants are enriched for expression Quantitative Trait Loci (eQTLs) and CREs in specific tissues or cells. As such, data derived from previous research endeavors may not capture fully cell-type and/or region specific changes associated with brain diseases. Coupling recent technological advances in genomics with cell-type specific methodologies, we are presented with an unprecedented opportunity to better understand the genetics of normal brain development and function and, in turn, the molecular basis of neuropsychiatric disorders. In this review, we will outline ongoing efforts towards this goal and will discuss approaches with the potential to shed light on the mechanism(s) of action of cell-type specific cis regulatory elements and their putative roles in disease, with particular emphasis on understanding the manner in which the epigenome and CREs influence the etiology of SCZ.
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Fullard
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Halene
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Giambartolomei
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Schahram
authors.initials: S
authors.lastname: Akbarian
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA. Electronic address: Panagiotis.roussos@mssm.edu.
authors.forename: Panos
authors.initials: P
authors.lastname: Roussos
mesh_terms: D001921:Brain / Q000254:growth & development / Q000378:metabolism; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism
keywords: Brain; Chromatin; Epigenetics; Gene expression; Postmortem
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