{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:14:59Z","timestamp":1768569299473,"version":"3.49.0"},"posted":{"date-parts":[[2025,9,10]]},"group-title":"Genetic and Genomic Medicine","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,10]]},"abstract":"<jats:p>Background: The perinatal period is a high-risk time for onset of various psychiatric disorders. However, it is\nunclear how genetic risk factors for these disorders interact with biological changes associated with pregnancy\nand postpartum. This study evaluates whether psychiatric genome-wide association study (GWAS) results are\nenriched within various brain regions across the perinatal period.\nMethods: Tissue-specific enrichment analyses were conducted to estimate the potential impact of GWAS loci\non transcriptional changes in the brain across the perinatal period. GWAS summary statistics were obtained\nfor 26 psychiatric phenotypes. RNA-sequencing data was acquired from four brain regions (hypothalamus,\nhippocampus, cerebellum, and neocortex) in mice at six timepoints (virgin, 14- and 16-days post-conception,\nand 1-, 3- and 10-days postpartum).\nResults: Hippocampus and neocortex in the early postpartum period are significantly enriched (q-value &lt; 0.05)\nfor genetic variants associated with schizophrenia (SCZ), bipolar disorder (BD), depressive symptoms, and\nmajor depressive disorder with suicidal features. The most significant enrichment occurred in the neocortex\nfor 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\nhippocampus, BD and SCZ were enriched at postpartum day 1 (SCZ p-value = 3.27 x 10-3; BD p-value = 4.33 x\n10-3). No enrichment was observed in cerebellum or hypothalamus for any of the psychiatric traits tested.\nConclusions: The results accord with previous epidemiological studies and provide context in which to interpret\nGWAS results. Understanding the burden of genetic variants across the perinatal period may help prioritise\npathways underlying onset of psychiatric disorders outside of pregnancy and postpartum periods.<\/jats:p>","DOI":"10.1101\/2025.09.07.25335185","type":"posted-content","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T18:45:19Z","timestamp":1757529919000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiple Psychiatric Traits Enriched for Brain Tissues in the Early Postpartum Period"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7432-3353","authenticated-orcid":false,"given":"Natasha","family":"Berthold","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-4470","authenticated-orcid":false,"given":"Shuyang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-1101","authenticated-orcid":false,"given":"Jerry","family":"Guintivano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.07.25335185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:45:16Z","timestamp":1768509916000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.09.07.25335185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1101\/2025.09.07.25335185","relation":{},"subject":[],"published":{"date-parts":[[2025,9,10]]},"subtype":"preprint"}}