LAUSR

Background Obstetric Complications (OC) have been implicated in the aetiology of psychiatric disorders, and are hypothesised to interact with underlying genetics to increase risk. We undertook a genome-wide search of interactions with OCs for psychopathology and personality traits related to psychiatric disorders in the Generation Scotland cohort. Methods OCs were obtained using medical record linkage. We used general linear models to test for interactions between OCs (birth-weight, labour induction, Caesarean section, use of forceps, gestational age and neonatal care admission) and over 500,000 SNPs on measures of psychopathology (General Health Questionnaire (GHQ), Schizotypal Personality Questionnaire (SPQ), Mood Disorder Questionnaire (MDQ) and personality (Eysenck Extraversion and Introversion) as outcomes. Numbers for each OC analysis were based on the availability of medical records. Results All p-values reported are after Bonferroni correction. Genome-wide significant SNP-OC interactions were observed for the GHQ with neonatal care admission (N=1539; rs17141144; p=6.70×10-7; LOC107986773; intronic), use of forceps (N=1669; rs17065704; p=3.24×10-6; PEX7; intronic) and birthweight (N=2420; rs9608151; p=0.02; intergenic). GWAS-significant interactions were also found for the SPQ with neonatal care admission (N=932; rs12512245; p=0.02; intergenic) and birthweight (N=1536; rs7803908, p=0.005; TNS3; intronic) and for Eysenck Extraversion with birthweight (N=2629; rs7137811; p=0.007; intergenic) and gestational age (N=1541; rs17708877; p=0.01; DGKB; intronic). Discussion To our knowledge, this is the first genome-wide study to reveal GWAS-significant gene-by-environment interactions with OCs impact a wide variety of psychological traits associated with psychiatric disorders. As the OC data were obtained via medical record linkage, they are not likely to suffer from recall bias. Genes implicated include PEX7, involved in neuronal migration, and DGKB, highly expressed in the hippocampus and linked to cognition and schizophrenia.