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Around 40% of people who are treated with antipsychotics could develop extrapyramidal side-effects (EPSE) including: (1) Dyskinesia, (2) Parkinsonism, (3) Akathisia, and (4) Dystonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to identify genetic risk factors for EPSE presence following antipsychotic treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted Genome-wide association (GWAS) and Epigenome-wide association (EWAS) meta-analyses of EPSE, with subset analyses separating first and second generation antipsychotic (FGA\/SGA) exposure. We integrated significant EWAS findings from a between-case design to a comparable GWAS for association enrichment. We investigated whether polygenic risk scores (PRS) for schizophrenia, Parkinson\u2019s disease, and Lewy-body dementia could predict EPSE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The primary GWAS top SNP rs2709733 (A\/G) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20095.755\u2009\u00d7\u200910\n                      <jats:sup>\u221207<\/jats:sup>\n                      ) mapped to a long intergenic non-protein coding RNA,\n                      <jats:italic>LINC01162<\/jats:italic>\n                      with consistent effects across all cohorts. Subset analyses with distinct FGA exposure indicated suggestive genes such as\n                      <jats:italic>NAV2<\/jats:italic>\n                      ,\n                      <jats:italic>NRG3<\/jats:italic>\n                      ,\n                      <jats:italic>LSAMP<\/jats:italic>\n                      and SGA exposure indicated\n                      <jats:italic>SHISA9<\/jats:italic>\n                      and\n                      <jats:italic>CNBD1<\/jats:italic>\n                      which are relevant for schizophrenia, autism, and epilepsy. In our primary EWAS, the most significant differentially methylated position (DMP) was cg05599348 (3.181\u2009\u00d7\u200910\n                      <jats:sup>\u221207<\/jats:sup>\n                      ), located at chrX:103,174,718 (hg19) mapping to\n                      <jats:italic>TMSB15B<\/jats:italic>\n                      . Comparing EPSE cases to healthy controls, we identified nine DMPs associated with EPSE. The DMP cg12044923 (chr2:241453995, hg19), located within the\n                      <jats:italic>STK32B<\/jats:italic>\n                      gene, showed significant enrichment for EPSE association (permutation\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010).\n                      <jats:italic>STK32B<\/jats:italic>\n                      is relevant to both psychiatric and movement disorders, suggesting potential shared mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study sheds new light on the potential biological mechanisms underlying EPSE development in schizophrenia, highlighting the importance of exploring both methylation changes and SNP associations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-025-06912-w","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:08:09Z","timestamp":1760152089000},"page":"1631-1642","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating genome-wide and epigenome-wide associations for antipsychotic induced extrapyramidal side effects"],"prefix":"10.1007","volume":"243","author":[{"given":"Kai","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan H.","family":"Thygesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan K.","family":"Lock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio F.","family":"Pardi\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia L.","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israa","family":"Elbashir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Lodhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain-Ul-Abideen","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"O\u2019Donovan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T. 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