{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:53:46Z","timestamp":1768564426582,"version":"3.49.0"},"posted":{"date-parts":[[2023,9,18]]},"group-title":"Neurology","reference-count":30,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Epilepsy is highly heritable, with numerous known genetic risk loci. However, the genetic predisposition\u2019s role in post-acute brain injury epilepsy remains understudied. This study assesses whether a higher genetic predisposition to epilepsy raises post-stroke or Transient Ischemic Attack (TIA) survivor\u2019s risk of Post-Stroke Epilepsy (PSE).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We conducted a three-stage genetic analysis. First, we identified independent epilepsy-associated (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;5x10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) genetic variants from public data. Second, we estimated PSE-specific variant weights in stroke\/TIA survivors from the UK Biobank. Third, we tested for an association between a polygenic risk score (PRS) and PSE risk in stroke\/TIA survivors from the All of Us Research Program. Primary analysis included all ancestries, while a secondary analysis was restricted to European ancestry only. A sensitivity analysis excluded TIA survivors. Association testing was conducted via multivariable logistic regression, adjusting for age, sex, and genetic ancestry.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 19,708 UK Biobank participants with stroke\/TIA, 805 (4.1%) developed PSE. Likewise, among 12,251 All of Us participants with stroke\/TIA, 394 (3.2%) developed PSE. After establishing PSE-specific weights for 39 epilepsy-linked genetic variants in the UK Biobank, the resultant PRS was associated with elevated odds of PSE development in All of Us (OR:1.16[1.02-1.32]). A similar result was obtained when restricting to participants of European ancestry (OR:1.23[1.02-1.49]) and when excluding participants with a TIA history (OR:1.18[1.02-1.38]).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings suggest that akin to other forms of epilepsy, genetic predisposition plays an essential role in PSE. Because the PSE data were sparse, our results should be interpreted cautiously.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.09.18.23295739","type":"posted-content","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:25:16Z","timestamp":1695090316000},"source":"Crossref","is-referenced-by-count":4,"title":["Polygenic Risk of Epilepsy and Post-Stroke Epilepsy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-1829","authenticated-orcid":false,"given":"Cyprien 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