{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:14:04Z","timestamp":1788459244136,"version":"build-2803163510"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":237,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01NR015591"],"award-info":[{"award-number":["R01NR015591"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 NS114045"],"award-info":[{"award-number":["R01 NS114045"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NS\/NINDS NIH HHS"},{"DOI":"10.13039\/100000968","name":"AHA","doi-asserted-by":"publisher","award":["23CSA1052295"],"award-info":[{"award-number":["23CSA1052295"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"AHA","doi-asserted-by":"publisher","award":["VA-Merit BX004672-04"],"award-info":[{"award-number":["VA-Merit BX004672-04"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"name":"US Dept. of Veterans Affairs\u2014Biomedical Laboratory Research and Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Stroke is a major cause of long-term disability with variable recovery. While clinical factors such as initial severity play a role, genetic factors are increasingly recognized as important contributors to stroke recovery. Genotype studies are generally focused on a single post-stroke behavioural domain, but some genes might relate to broad mechanisms of plasticity. This study therefore aimed to identify cross-phenotypic genetic variants associated across two or more stroke recovery domains. DNA from Stroke, Stress, Rehabilitation, and Genetics study participants was genotyped, resulting in 9 814 610 variants. In order to examine cross-phenotypic results, we first conducted genome-wide association studies on the six recovery domains: motor (grip force), cognition (Telephone Montreal Cognitive Assessment), depression (Patient Health Questionnaire-8), stress (Primary Care Post-Traumatic Stress Disorder Screen), functional status (Stroke Impact Scale-Activities of Daily Living), and disability (modified Rankin Scale 0\u20132 versus 3\u20136), some of which were tested longitudinally, yielding nine phenotypes. Models were adjusted for age, sex, initial severity (NIH Stroke Scale score), and ancestry. Cross-phenotype associations were identified by evaluating single nucleotide polymorphisms (SNPs) associated (P &amp;lt; 5e-5) with multiple phenotypes. To determine how these genetic variants may relate to biological mechanisms of recovery, we conducted gene enrichment analyses. Participants (n = 565, 59% male) had mild-moderate initial stroke severity (median acute NIH Stroke Scale score = 4). After accounting for the correlation structure among the nine phenotypes, we observed 319 cross-phenotypic SNPs, 3.45 times the expected number. Five of the cross-phenotypic SNPs were linked to genes relevant to neural development, function and plasticity, e.g. ERICH1 (rs11778883-C), FOX3 (rs55726768-G), LIFR-AS1 (rs76401391-T), RPS6KA2 (rs113518460-C) and TUBGCP2 (rs147150392-C), as were enrichments in RAB5\u2013EEA1, CTNNA1\u2013CTNNB1, CIN85\u2013SH3GL2 and ELMO1\u2013DOCK2 complexes. Multiple gene enrichments were found, e.g. Stroke Impact Scale-Activities of Daily Living and Patient Health Questionnaire 8 at 3 months were enriched for CREB phosphorylation, which is important for long-term potentiation. We identified cross-phenotypic SNPs associated with multiple behavioural domains of stroke recovery. Some of these genes encode, or regulate, druggable proteins. These genetic factors are not well captured by clinical or neuroimaging assessments and so provide a unique window into stroke recovery. These findings, if validated, suggest that some genes may be broadly important to stroke recovery.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag322","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:41:49Z","timestamp":1787658109000},"source":"Crossref","is-referenced-by-count":0,"title":["Genomic insights into stroke recovery: cross-phenotype associations"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0539-9762","authenticated-orcid":false,"given":"Chad","family":"Aldridge","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Virginia , Charlottesville, VA 22908 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robynne","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Parodi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Genomic Medicine, McCance Center for Brain Health, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-3887","authenticated-orcid":false,"given":"Keith","family":"Lohse","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy, Department of Neurology, Washington University , St. Louis, MO 63108 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Edwardson","sequence":"additional","affiliation":[{"name":"Department of Neurology and Rehabilitation Medicine, Georgetown University , Washington, DC 20007 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Maryland School of Medicine , Baltimore, MD 21201 ,","place":["USA"]},{"name":"Department of Neurology, Baltimore Veterans Affairs Medical Center , Baltimore, MD 21201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne G","family":"Lindgren","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sk\u00e5ne University Hospital , Lund 29189 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Chi","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine , Winston-Salem, NC 27101 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Keene","sequence":"additional","affiliation":[{"name":"Department of Biology, East Carolina University , Greenville, NC 27858 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford","family":"Worrall","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Virginia , Charlottesville, VA 22908 ,","place":["USA"]},{"name":"Department of Public Health Sciences, University of Virginia , Charlottesville, VA 22908 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Rosand","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Genomic Medicine, McCance Center for Brain Health, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E Alison","family":"Holman","sequence":"additional","affiliation":[{"name":"Sue & Bill Gross School of Nursing and Department of Psychological Science, University of California, Irvine , Irvine, CA 92697 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C","family":"Cramer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California , Los Angeles, CA 90095-1769 ,","place":["USA"]},{"name":"California Rehabilitation Institute , Los Angeles, CA 90067 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"2026090313252640500_fcag322-B1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart disease and stroke statistics\u20142019 update: A report from the American Heart 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