Genetic overlap between epilepsy and schizophrenia: Evidence from cross phenotype analysis in Hong Kong Chinese population

Am J Med Genet B Neuropsychiatr Genet. 2018 Jan;177(1):86-92. doi: 10.1002/ajmg.b.32607. Epub 2017 Nov 17.

Abstract

Epilepsy and schizophrenia are common and typical neurological or mental illness respectively, and sometimes they comorbid in the same patients, however the underlying genetic relationship between the two brain diseases is still not fully understood. To investigate the possible genetic contribution to their comorbidity, we performed polygenic risk score (PRS) analyses and genetic correlation estimation so as to identify the overall genetic overlap between the two diseases. The global schizophrenia PRS is strongly associated with schizophrenia phenotype in Hong Kong population (odds ratio = 1.7, p = 2.26E-16), and focal epilepsy PRS is moderately associated with epilepsy phenotype in Hong Kong population (odds ratio = 1.14, p = 0.013). However the disease-specific PRS can only predict its own well-matched phenotype but not the other ones (p > 0.05). This pattern is further supported by non-significant pairwise genetic correlation and insufficient statistical power for PRS association from the cross-phenotype analyses. Our study reveals there's limited shared genetic aetiology between schizophrenia and epilepsy, and thus supports a model of shared environmental factors to explain the comorbidity between the two phenotypes.

Keywords: GWAS; comorbidity; genetic sharing; polygenic risk score.

MeSH terms

  • Adult
  • Asian People / genetics
  • Comorbidity
  • Epilepsy / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods
  • Hong Kong / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Multifactorial Inheritance / genetics
  • Odds Ratio
  • Phenotype
  • Risk Factors
  • Schizophrenia / genetics*