{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T15:03:01Z","timestamp":1785250981098,"version":"3.55.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Previous studies have integrated genome\u2010wide association studies with expression quantitative trait locus (eQTL) data from bulk tissues to identify stroke susceptibility genes. However, eQTL data exhibit high cell\u2010type specificity, and genetic variants may have distinct effects across stroke subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We applied the summary\u2010data\u2010based Mendelian randomization (MR) method to integrate eQTL data from 7 brain cell types with genome\u2010wide association studies data for 5 stroke phenotypes (stroke, ischemic stroke, cardioembolic stroke, large artery stroke, and small vessel stroke). Results were compared with summary\u2010data\u2010based MR using eQTL data from 49 tissues in the Genotype\u2010Tissue Expression project. Robustness of significant single\u2010cell summary\u2010data\u2010based MR associations was assessed via MR and colocalization analyses. Further evaluations included single\u2010cell RNA\u2010seq differential expression, protein\u2013protein interaction, druggability, and phenome\u2010wide association studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Single\u2010cell summary\u2010data\u2010based MR identified many novel significant genes not detected using bulk tissue eQTL data. Validated associations revealed 2 stroke risk genes (\n                      <jats:italic toggle=\"no\">LRCH1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">ICA1L<\/jats:italic>\n                      ), 3 stroke protective genes (\n                      <jats:italic toggle=\"no\">AHI1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">LYRM9<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">CENPQ<\/jats:italic>\n                      ), 2 large artery stroke risk genes (\n                      <jats:italic toggle=\"no\">LIPA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">ELL<\/jats:italic>\n                      ), and 1 ischemic stroke protective gene (\n                      <jats:italic toggle=\"no\">CENPQ<\/jats:italic>\n                      ). Single\u2010cell RNA\u2010seq showed significantly increased\n                      <jats:italic toggle=\"no\">LIPA<\/jats:italic>\n                      expression in mouse stroke samples compared with controls. Protein\u2013protein interaction and druggability analyses, along with phenome\u2010wide association studies, prioritized\n                      <jats:italic toggle=\"no\">LIPA<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"no\">LRCH1<\/jats:italic>\n                      as potential therapeutic targets for stroke while indicating possible adverse effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Integrating single\u2010cell eQTL with stroke\u2010subtype genome\u2010wide association studies uncovers novel cell\u2010type\u2010specific causal genes and highlights promising therapeutic targets, advancing understanding of stroke pathogenesis.<\/jats:p>\n                  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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-7676","authenticated-orcid":false,"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical College","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingshui","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Public Health, Wannan Medical College","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1126-2888","authenticated-orcid":false,"given":"Guiyou","family":"Liu","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]},{"name":"School of Public Health, Wannan Medical College","place":["Wuhu, China"]},{"name":"Shengli Oilfield Central Hospital","place":["Dongying, China"]},{"name":"Chengdu University of Traditional Chinese 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