{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:45:17Z","timestamp":1787237117151,"version":"build-2736575974"},"reference-count":61,"publisher":"Cambridge University Press (CUP)","issue":"16","license":[{"start":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T00:00:00Z","timestamp":1684800000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S0033291723001423_sec_a1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Observational studies suggest a correlation between post-traumatic stress disorder (PTSD) and gastrointestinal tract (GIT) disorders. However, the genetic overlap, causal relationships, and underlining mechanisms between PTSD and GIT disorders were absent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291723001423_sec_a2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We obtained genome-wide association study statistics for PTSD (23 212 cases, 151 447 controls), peptic ulcer disease (PUD; 16 666 cases, 439 661 controls), gastroesophageal reflux disease (GORD; 54 854 cases, 401 473 controls), PUD and\/or GORD and\/or medications (PGM; 90 175 cases, 366 152 controls), irritable bowel syndrome (IBS; 28 518 cases, 426 803 controls), and inflammatory bowel disease (IBD; 7045 cases, 449 282 controls). We quantified genetic correlations, identified pleiotropic loci, and performed multi-marker analysis of genomic annotation, fast gene-based association analysis, transcriptome-wide association study analysis, and bidirectional Mendelian randomization analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291723001423_sec_a3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PTSD globally correlates with PUD (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>g<\/jats:sub>\n                      = 0.526,\n                      <jats:italic>p<\/jats:italic>\n                      = 9.355 \u00d7 10\n                      <jats:sup>\u22127<\/jats:sup>\n                      ), GORD (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>g<\/jats:sub>\n                      = 0.398,\n                      <jats:italic>p<\/jats:italic>\n                      = 5.223 \u00d7 10\n                      <jats:sup>\u22129<\/jats:sup>\n                      ), PGM (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>g<\/jats:sub>\n                      = 0.524,\n                      <jats:italic>p<\/jats:italic>\n                      = 1.251 \u00d7 10\n                      <jats:sup>\u221215<\/jats:sup>\n                      ), and IBS (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>g<\/jats:sub>\n                      = 0.419,\n                      <jats:italic>p<\/jats:italic>\n                      = 8.825 \u00d7 10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). Cross-trait meta-analyses identify seven genome-wide significant loci between PTSD and PGM (rs13107325, rs1632855, rs1800628, rs2188100, rs3129953, rs6973700, and rs73154693); three between PTSD and GORD (rs13107325, rs1632855, and rs3132450); one between PTSD and IBS\/IBD (rs4937872 and rs114969413, respectively). Proximal pleiotropic genes are mainly enriched in immune response regulatory pathways, and in brain, digestive, and immune systems. Gene-level analyses identify five candidates:\n                      <jats:italic>ABT1<\/jats:italic>\n                      ,\n                      <jats:italic>BTN3A2<\/jats:italic>\n                      ,\n                      <jats:italic>HIST1H3J<\/jats:italic>\n                      ,\n                      <jats:italic>ZKSCAN4<\/jats:italic>\n                      , and\n                      <jats:italic>ZKSCAN8<\/jats:italic>\n                      . We found significant causal effects of GORD, PGM, IBS, and IBD on PTSD. We observed no reverse causality of PTSD with GIT disorders, except for GORD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S0033291723001423_sec_a4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PTSD and GIT disorders share common genetic architectures. Our work offers insights into the biological mechanisms, and provides genetic basis for translational research studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/s0033291723001423","type":"journal-article","created":{"date-parts":[[2023,5,23]],"date-time":"2023-05-23T06:28:05Z","timestamp":1684823285000},"page":"7627-7635","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":11,"title":["Investigating the shared genetic architecture of post-traumatic stress disorder and gastrointestinal tract disorders: a genome-wide cross-trait 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