Background: The perinatal period is a high-risk time for onset of various psychiatric disorders. However, it is unclear how genetic risk factors for these disorders interact with biological changes associated with pregnancy and postpartum. This study evaluates whether psychiatric genome-wide association study (GWAS) results are enriched within various brain regions across the perinatal period. Methods: Tissue-specific enrichment analyses were conducted to estimate the potential impact of GWAS loci on transcriptional changes in the brain across the perinatal period. GWAS summary statistics were obtained for 26 psychiatric phenotypes. RNA-sequencing data was acquired from four brain regions (hypothalamus, hippocampus, cerebellum, and neocortex) in mice at six timepoints (virgin, 14- and 16-days post-conception, and 1-, 3- and 10-days postpartum). Results: Hippocampus and neocortex in the early postpartum period are significantly enriched (q-value < 0.05) for genetic variants associated with schizophrenia (SCZ), bipolar disorder (BD), depressive symptoms, and major depressive disorder with suicidal features. The most significant enrichment occurred in the neocortex for SCZ and BD, peaking at postpartum day 1 (SCZ p-value = 3.85 x 10-8; BD p-value = 6.65 x 10-5). In the hippocampus, BD and SCZ were enriched at postpartum day 1 (SCZ p-value = 3.27 x 10-3; BD p-value = 4.33 x 10-3). No enrichment was observed in cerebellum or hypothalamus for any of the psychiatric traits tested. Conclusions: The results accord with previous epidemiological studies and provide context in which to interpret GWAS results. Understanding the burden of genetic variants across the perinatal period may help prioritise pathways underlying onset of psychiatric disorders outside of pregnancy and postpartum periods.

The authors have declared no competing interest.

J Guintivano would like to acknowledge National Institute of Mental Health grant K01MH116413. N Berthold would like to acknowledge a fellowship awarded by the Centre of Excellence for Eating Disorders University of North Carolina at Chapel Hill, the Quad Fellowship awarded by the Institute of International Education, and an Australian Research Training Scholarship provided by the University of Western Australia.

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All data used in this study are free and publicly available. Raw RNA-seq data were obtained from NCBI Gene Expression Omnibus (accession GSE70732). European ancestry GWAS summary statistics were obtained from the PGC website (https://pgc.unc.edu/for-researchers/download-results/). Gene ontology terms were downloaded from the Gene Ontology database (geneontology.org).

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All data used in this study are free and publicly available. Raw RNA-seq data were obtained from NCBI Gene Expression Omnibus (accession GSE70732). European ancestry GWAS summary statistics were obtained from the PGC website (https://pgc.unc.edu/for-researchers/download-results/). Gene ontology terms were downloaded from the Gene Ontology database (geneontology.org).