Genetic underpinnings of schizophrenia-related electroencephalographical intermediate phenotypes: A systematic review and meta-analysis

Abstract

Although substantial research into genetics of psychotic disorders has been conducted, a large proportion of their genetic architecture has remained unresolved. Electroencephalographical intermediate phenotypes (EIP) have the potential to constitute a valuable tool when studying genetic risk loci for schizophrenia, in particular P3b amplitude, P50 suppression, mismatch negativity (MMN) and resting state power spectra of the electroencephalogram (EEG). Here, we systematically reviewed studies investigating the association of single nucleotide polymorphisms (SNPs) with these EIPs and meta-analysed them when appropriate. We retrieved 45 studies (N = 34,971 study participants). Four SNPs investigated in more than one study were genome-wide significant for an association with schizophrenia and three were genome-wide suggestive, based on a lookup in the influential 2014 GWAS (Ripke et al., 2014). However, in our meta-analyses, rs1625579 failed to reach a statistically significant association with p3b amplitude decrease and rs4680 risk allele carrier status was not associated with p3b amplitude decrease or with impaired p50 suppression. In conclusion, evidence for SNP associations with EIPs remains limited to individual studies. Careful selection of EIPs and SNPs, combined with consistent reporting of effect sizes, directions of effect and p-values would aid future meta-analyses.