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Int. J. Mol. Sci. 2017, 18(3), 527; doi:10.3390/ijms18030527

GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia

1
Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA
2
Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 18 January 2017 / Revised: 15 February 2017 / Accepted: 23 February 2017 / Published: 28 February 2017
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Abstract

Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2). Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction. View Full-Text
Keywords: mental illness; genetic profiling; GeneAnalytics molecular pathway analysis; circadian entrainment mental illness; genetic profiling; GeneAnalytics molecular pathway analysis; circadian entrainment
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Khanzada, N.S.; Butler, M.G.; Manzardo, A.M. GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia. Int. J. Mol. Sci. 2017, 18, 527.

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