Frontiers in Cell and Developmental Biology (Jul 2022)

Patterns of Convergence and Divergence Between Bipolar Disorder Type I and Type II: Evidence From Integrative Genomic Analyses

  • Yunqi Huang,
  • Yunqi Huang,
  • Yunqi Huang,
  • Yunjia Liu,
  • Yunjia Liu,
  • Yunjia Liu,
  • Yulu Wu,
  • Yulu Wu,
  • Yulu Wu,
  • Yiguo Tang,
  • Yiguo Tang,
  • Yiguo Tang,
  • Mengting Zhang,
  • Mengting Zhang,
  • Mengting Zhang,
  • Siyi Liu,
  • Siyi Liu,
  • Siyi Liu,
  • Liling Xiao,
  • Liling Xiao,
  • Liling Xiao,
  • Shiwan Tao,
  • Shiwan Tao,
  • Shiwan Tao,
  • Min Xie,
  • Min Xie,
  • Min Xie,
  • Minhan Dai,
  • Minhan Dai,
  • Minhan Dai,
  • Mingli Li,
  • Mingli Li,
  • Mingli Li,
  • Hongsheng Gui,
  • Hongsheng Gui,
  • Qiang Wang,
  • Qiang Wang,
  • Qiang Wang

DOI
https://doi.org/10.3389/fcell.2022.956265
Journal volume & issue
Vol. 10

Abstract

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Aim: Genome-wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about the genetic structure of BD subtypes. We aimed to investigate the genetic overlap and distinction of bipolar type I (BD I) & type II (BD II) by conducting integrative post-GWAS analyses.Methods: We utilized single nucleotide polymorphism (SNP)–level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis, including exploring the potential causal associations between two BD subtypes and lithium responses and comparing the difference in genetic structures among four different psychiatric traits.Results: SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184, and RPL10AP3, shared by BD I and II, and one locus (MAD1L1) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes affecting BD I and II through expression in specific brain regions (nucleus accumbens for BD I). Cross-phenotype analyses indicated that BD I and II share continuous genetic structures with schizophrenia and major depressive disorder, which help fill the gaps left by the dichotomy of mental disorders.Conclusion: These combined evidences illustrate genetic convergence and divergence between BD I and II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.

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