Genome-Wide Associations of Schizophrenia Studied with Computer Simulation

  • Samuel A. NeymotinEmail author
  • Nathan S. Kline
  • Mohamed A. Sherif
  • Jeeyune Q. Jung
  • Joseph J. Kabariti
  • William W. Lytton
Part of the Springer Series in Computational Neuroscience book series (NEUROSCI)


A recent genome-wide association study (GWAS) demonstrated 108 association loci that are associated with development of schizophrenia (Schizophrenia Working Group, 2014). These are just the sites that can be implicated using the statistical power conferred by current data. It is expected that many more sites will be uncovered as new studies use larger numbers of cases and controls. The number of likely associated loci is uncertain, but one estimate suggests it may be in the thousands (International Schizophrenia Consortium). For any given patient, only a small subset of these locations will show mutations. The clinical pathway hypothesis for polygenic diseases predicts that the various sites of damage associated with a given disease reflect sets of mutationally damaged genes that together produce the disease (we will use the term clinical pathway so as to distinguish it from the traditional definition of a pathway as a biochemical sequence) (Sullivan, 2012). What is a clinical pathway? This term remains weakly defined and will differ between diseases and even within a single disease. For example, multiple clinical pathways in schizophrenia may well involve (1) developmental sequences, (2) intracellular cascade sequences such as second-messenger cascades in neurons, (3) genetic activation sequences or RNA transcriptional control sequences, (4) immunological and scavenging pathways (e.g., synapse and cell elimination in schizophrenia Sullivan 2012), and (5) pathways of dynamical physiological interactions that together provide physiological activity.


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Samuel A. Neymotin
    • 1
    Email author
  • Nathan S. Kline
    • 2
  • Mohamed A. Sherif
    • 3
    • 4
    • 5
  • Jeeyune Q. Jung
    • 5
  • Joseph J. Kabariti
    • 5
  • William W. Lytton
    • 6
    • 5
  1. 1.Department of NeuroscienceBrown UniversityProvidenceUSA
  2. 2.Institute for Psychiatric ResearchOrangeburgUSA
  3. 3.Yale UniversityNew HavenUSA
  4. 4.VA Connecticut Healthcare SystemWest HavenUSA
  5. 5.Department Physiology and PharmacologySUNY DownstateBrooklynUSA
  6. 6.Department NeurologyKings County Hospital CenterBrooklynUSA

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