An Integrative Computational Approach to Evaluate Genetic Markers for Bipolar Disorder

Sci Rep. 2017 Jul 27;7(1):6745. doi: 10.1038/s41598-017-05846-4.


Studies to date have reported hundreds of genes connected to bipolar disorder (BP). However, many studies identifying candidate genes have lacked replication, and their results have, at times, been inconsistent with one another. This paper, therefore, offers a computational workflow that can curate and evaluate BP-related genetic data. Our method integrated large-scale literature data and gene expression data that were acquired from both postmortem human brain regions (BP case/control: 45/50) and peripheral blood mononuclear cells (BP case/control: 193/593). To assess the pathogenic profiles of candidate genes, we conducted Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analyses, with 4 metrics proposed and validated for each gene. Our approach developed a scalable BP genetic database (BP_GD), including BP related genes, drugs, pathways, diseases and supporting references. The 4 metrics successfully identified frequently-studied BP genes (e.g. GRIN2A, DRD1, DRD2, HTR2A, CACNA1C, TH, BDNF, SLC6A3, P2RX7, DRD3, and DRD4) and also highlighted several recently reported BP genes (e.g. GRIK5, GRM1 and CACNA1A). The computational biology approach and the BP database developed in this study could contribute to a better understanding of the current stage of BP genetic research and assist further studies in the field.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / physiopathology
  • Brain / metabolism
  • Brain / physiopathology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Case-Control Studies
  • Computational Biology / methods*
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Markers*
  • Genetic Predisposition to Disease
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Male
  • Metabolic Networks and Pathways / genetics
  • Middle Aged
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Neurotransmitter Transport Proteins / genetics*
  • Neurotransmitter Transport Proteins / metabolism
  • Receptors, Neurotransmitter / genetics*
  • Receptors, Neurotransmitter / metabolism
  • Synapses / metabolism
  • Synapses / pathology
  • Synaptic Transmission


  • Calcium Channels
  • Genetic Markers
  • Nerve Growth Factors
  • Neurotransmitter Transport Proteins
  • Receptors, Neurotransmitter