{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:18:22Z","timestamp":1787811502726,"version":"build-2784847793"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early pregnancy bleeding is a common pregnancy complication, yet its genetic basis and potential links with psychiatric traits remain poorly understood. This study aimed to characterize the shared genetic architecture between early pregnancy bleeding and reproductive, psychiatric, and cardiometabolic traits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated linkage disequilibrium score regression (LDSC), local genetic correlation analysis (LAVA), and multi-trait genome-wide association analysis (MTAG). LDSC was used to estimate genome-wide genetic correlations, including sex-stratified analyses. LAVA was applied to identify genomic regions contributing to local genetic sharing. Guided by these correlation patterns, MTAG was performed to improve locus discovery, followed by cis-eQTL analysis using GTEx v8 to explore potential regulatory mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LDSC revealed significant positive genetic correlations between early pregnancy bleeding and reproductive traits, including endometriosis, miscarriage, and uterine fibroids. Strong positive correlations were also observed with several psychiatric disorders, including major depressive disorder, post-traumatic stress disorder, and attention deficit hyperactivity disorder. Sex-stratified analyses suggested stronger genetic correlations with emotional reactivity-related traits in females, whereas social and behavioral traits were more prominent in males. LAVA localized these shared signals to specific genomic regions and identified pleiotropic hotspots at 8q21 near\n                      <jats:italic>RUNX1T1<\/jats:italic>\n                      and 9p21 near\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      . MTAG identified two novel loci, 15q15.1 marked by rs45457497 and 11q13.1 marked by rs2452681. Cis-eQTL analysis showed that the lead variant at 15q15.1 regulates\n                      <jats:italic>RMDN3<\/jats:italic>\n                      expression across multiple brain regions, while the 11q13.1 locus regulates\n                      <jats:italic>PACS1, GAL3ST3<\/jats:italic>\n                      , and\n                      <jats:italic>SF3B2<\/jats:italic>\n                      expression in brain tissues and the pituitary.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings position early pregnancy bleeding as a multifactorial trait shaped by shared reproductive, psychiatric, neuroendocrine, and stress-related biology. The implication of\n                      <jats:italic>RMDN3<\/jats:italic>\n                      , which encodes a mitochondrial outer membrane protein involved in ER-mitochondria tethering and calcium homeostasis, suggests a potential molecular link between neuroendocrine stress pathways, psychiatric susceptibility, and reproductive vulnerability.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1911755","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:34:53Z","timestamp":1787808893000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-trait GWAS identifies pleiotropic loci shared between early pregnancy bleeding and psychiatric traits"],"prefix":"10.3389","volume":"17","author":[{"given":"Deyu","family":"Ji","sequence":"first","affiliation":[{"name":"First Clinical Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianjin","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Medical Information and Artificial Intelligence, Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Medical Information and Artificial Intelligence, Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunchen","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Medical Information and Artificial Intelligence, Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Medical Information and Artificial Intelligence, Shandong First Medical University","place":["Jinan, Shandong, China"]},{"name":"Shandong Engineering Research Center of Intelligent Surgery, The First Affiliated Hospital of Shandong First Medical University","place":["Jinan, China"]},{"name":"Shandong Data Open Innovative Application Laboratory, The First Affiliated Hospital of Shandong First Medical University","place":["Jinan, China"]},{"name":"Shandong Key Laboratory of Digital Diagnosis and Treatment of Thoracic Oncology, The First Affiliated Hospital of Shandong First Medical University","place":["Jinan, China"]},{"name":"China Foundation for Youth Entrepreneurship and Employment-Incaier Public Welfare Fund","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1513247","article-title":"Postpartum 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