{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T23:25:21Z","timestamp":1791761121902,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Previous studies have suggested that hypoxia\u2010inducible factor 1\u2010\u03b1 (HIF\u20101\u03b1) exerted multiple effects on different central nervous system disorders. However, it is still uncertain whether plasma HIF\u20101\u03b1 can be a causal indicator for the relevant diseases. This study aimed to test the causality relationship between plasma HIF\u20101\u03b1 and neurological diseases, including cerebrovascular diseases, migraines, and neurodegenerative diseases with a Mendelian randomization (MR) method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010nucleotide polymorphisms (SNPs) genetically representing plasma HIF\u20101\u03b1 were screened as instrumental variables (IVs). Summary\u2010level data for neurological disorder from genome\u2010wide association studies (GWAS) were identified as outcomes. The causal effects between the IVs and outcomes were determined via the major analysis of inverse\u2010variance\u2010weighted (IVW) method. The reverse causal direction was also performed to investigate the possibility of reverse causation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The findings revealed that plasma HIF\u20101\u03b1 was identified to be genetically associated with cardioembolic stroke (CES) (OR = 0.885; 95% confidence interval [CI] = 0.796\u20130.985,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.026), migraine (OR = 0.941, 95% CI = 0.888\u20130.998,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.041), and drug\u2010induced migraine without aura (MOA) (OR = 0.586, 95% CI = 0.375\u20130.916,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.019). There was no association identified in plasma HIF\u20101\u03b1 with subarachnoid hemorrhage (SAH), other stroke and migraine subtype, and neurodegenerative disorders. The reverse\u2010MR analysis revealed that the above\u2010stated neurological diseases did not have a causal effect on plasma HIF\u20101\u03b1 levels. Sensitivity and validation analyses support that the above results are stable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our research indicated that plasma HIF\u20101\u03b1 may have a causal effect on the risk of CES, migraine and drug\u2010induced MOA, providing new insights for those disease prevention and therapeutic approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70398","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:42:30Z","timestamp":1741736550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Association Between Hypoxia\u2010Inducible Factor\u20101\u03b1 and Neurological Diseases: A Bidirectional Two\u2010Sample Mendelian Randomization Analysis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9713-4754","authenticated-orcid":false,"given":"Jing","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology Fujian Medical University  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital, Institute 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav7188"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00038-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01676-7"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04286"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01111-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12717"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02170-4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt179"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1072351"},{"issue":"11","key":"e_1_2_11_12_1","first-page":"5134","article-title":"Local 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