{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:14:52Z","timestamp":1771931692261,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Schizophrenia (SCZ) and post-traumatic stress disorder (PTSD) are severe psychiatric conditions with overlapping yet distinct symptomatology and pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a differential genome-wide association study (GWAS) to directly compare the genetic architectures of SCZ and PTSD using publicly available GWAS summary statistics from the Psychiatric Genomics Consortium (PGC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified four independent loci reaching genome-wide significance (P &amp;lt; 5 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      ) for differential associations between SCZ and PTSD in individuals of European ancestry. These loci (rs62062288, rs58120505, rs12536395, and rs11057189) showed genome-wide significant associations with SCZ and nominal associations with PTSD (all\n                      <jats:italic>P<\/jats:italic>\n                      s &amp;lt; 0.05) but with opposite directions of effect. Among these, only rs62062288 retained genome-wide significance for PTSD in trans-ancestry meta-analysis, whereas the other three loci showed markedly attenuated PTSD associations (all\n                      <jats:italic>P<\/jats:italic>\n                      s &amp;gt; 0.001). rs62062288 maps to the 17q21.31\n                      <jats:italic>MAPT<\/jats:italic>\n                      \/\n                      <jats:italic>CRHR1<\/jats:italic>\n                      locus, exhibiting a risk effect for PTSD and a protective effect for SCZ. GTEx analyses revealed that\n                      <jats:italic>MAPT<\/jats:italic>\n                      and\n                      <jats:italic>CRHR1<\/jats:italic>\n                      are highly expressed across multiple brain tissues and that rs62062288 shows opposite regulatory effects on\n                      <jats:italic>MAPT<\/jats:italic>\n                      and\n                      <jats:italic>CRHR1<\/jats:italic>\n                      expression in the brain tissue caudate basal ganglia, with the PTSD risk allele associated with increased\n                      <jats:italic>MAPT<\/jats:italic>\n                      expression and decreased\n                      <jats:italic>CRHR1<\/jats:italic>\n                      expression. Additional brain-region\u2013specific expression quantitative trait locus (eQTL) effects on\n                      <jats:italic>CRHR1<\/jats:italic>\n                      were observed in frontal cortex BA9, hippocampus, and spinal cord, indicating tissue-dependent regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings provide evidence for distinct and opposing genetic contributions to SCZ and PTSD. The identification of the\n                      <jats:italic>MAPT<\/jats:italic>\n                      \/\n                      <jats:italic>CRHR1<\/jats:italic>\n                      locus with brain-region\u2013specific and gene-specific regulatory effects highlights divergent neurodevelopmental and stress-related pathways underlying these disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1728494","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T22:10:11Z","timestamp":1770934211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential genome-wide association analysis of schizophrenia and post-traumatic stress disorder identifies opposing effects at the MAPT\/CRHR1 locus"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhong\u2010shan","family":"Cheng","sequence":"first","affiliation":[{"name":"Center for Applied Bioinformatics, St. Jude Children\u2019s Research Hospital","place":["Memphis, TN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1196\/annals.1347.016","article-title":"Estradiol prevents neural tau hyperphosphorylation characteristic of alzheimer's disease","volume":"1052","author":"Alvarez-de-la-Rosa","year":"2005","journal-title":"Ann. 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