Patterns of epilepsy-schizophrenia genetic correlation and sharing revealed by secondary analyses of GWAS data

Abstract

Epilepsy and schizophrenia is a common and typical neurological disorder or mental illness respectively. A patient suffering from epilepsy might have depression or another mental illness, and some forms of seizures may mimic the symptoms of psychosis. Better understanding of epilepsy can therefore provide insights on the understanding of mental illness like schizophrenia, and vice versa. However, there are few genetic loci found that predisposes to both two diseases from genome-wide association study (GWAS) on each individual phenotype. In this study, raw genotype data and summary statistics were collected from two previous epilepsy or schizophrenia GWAS on Chinese population. To investigate the genetic relationship between the two disorders, we calculated the overall genetic correlation by LD-score regression analyses and polygenic risk scores (PRS) projected on each other. In addition, we have searched for the shared susceptibility genetic hits by cross-phenotype analyses on three different levels (SNPs, genes and gene-sets). Non-significant low genetic correlation (r=-0.01, p>0.05) was found between these two disorders. PRS on different p-values for one phenotype cannot predict the other one. Genetic sharing was only found for one SNP located at 2p16.1 locus. This negative findings may mainly be due to lower power of epilepsy GWAS which only explain 7% phenotype variance. Large-scale consortia data on each phenotype from International league against epilepsy or Psychiatric genomic consortium are being collected so as to further examine the genetic correlation and sharing between them.