{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:38:04Z","timestamp":1792647484910,"version":"4.5.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke and premature mortality, with higher prevalence in specific ethnic groups. Multiple studies have evaluated the association of ICAD and genetic variants. This study aims to systematically review and summarize the current genetic contributors of ICAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta\u2010Analyses guidelines. Embase, MEDLINE, and Cochrane Library databases were searched from inception to September 2025 for human studies examining single\u2010nucleotide variants (SNVs) associations and ICAD. Three independent reviewers extracted data on study characteristics, SNVs, alleles and\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      values. SNVs reported in &gt;1 study were pooled using a fixed\u2010effects model. Expression quantitative trait loci analysis evaluated the regulatory effects of identified SNVs across brain and arterial tissue. Functional enrichment analysis was conducted to identify relevant biological pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Fourteen studies met inclusion criteria, comprising a total of 15\u2009535 individuals, of whom 3638 had ICAD. Across these studies, 35 SNVs were identified, mapping to 26 unique genes. In the pooled analysis, ICAD was associated with\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      rs112735431 (odds ratio, 18.61 [95% CI, 11.84\u201329.25]). Other SNVs were found in genes including\n                      <jats:italic toggle=\"no\">ADIPOQ<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">INSR<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"no\">NTNG1<\/jats:italic>\n                      . Functional enrichment highlighted lipid metabolism and triglyceride homeostasis pathways as key contributors to ICAD risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This review consolidates current evidence on SNVs associated with ICAD, highlighting\n                      <jats:italic toggle=\"no\">RNF213<\/jats:italic>\n                      rs112735431 as a major genetic contributor, particularly in East Asian populations. Further research is needed to clarify the functional roles of these variants and their potential as therapeutic targets.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.048672","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:56:25Z","timestamp":1791633385000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variants in Intracranial Atherosclerotic Disease: A Systematic Review and Targeted Meta\u2010Analysis Highlighting the\n                    <i>RNF213<\/i>\n                    rs112735431"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0117-9288","authenticated-orcid":false,"given":"Cameron","family":"Bass","sequence":"first","affiliation":[{"name":"University at Buffalo Jacobs School Medicine and Biomedical Sciences","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Wahlig","sequence":"additional","affiliation":[{"name":"Yale University","place":["New Haven, USA"]},{"name":"Neurosurgery, Gates Vascular Institute","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla","family":"Hickey","sequence":"additional","affiliation":[{"name":"University at Buffalo Jacobs School Medicine and Biomedical Sciences","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8310-0474","authenticated-orcid":false,"given":"Pui Man Rosalind","family":"Lai","sequence":"additional","affiliation":[{"name":"University at Buffalo Jacobs School Medicine and Biomedical Sciences","place":["Buffalo, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.02.050"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.011147"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.11.008"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.1.14"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.15.1.56"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.40.10.1540"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70234-X"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-020-0831-5"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14235969"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.27"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.3233\/DMA-2011-0810"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.08.034"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.012248"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2016.1190716"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2022.120218"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.06.043"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2018.10.050"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/genes12060815"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2021.11.095"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2021-001157"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-68888-1"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01049-w"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.663864"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2017.06.016"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221110679"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12010078"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3376"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000519717"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1159\/000540758"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2024.107982"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2010.09.001"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150531161138"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1159\/000338781"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1079\/pns19970072"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2011.1169"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0518"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep31945"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/313756a0"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15211"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab104"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae193"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1092431"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06540.2000"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.08.015"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.048672","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:52:35Z","timestamp":1792644755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.048672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":44,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10,20]]}},"alternative-id":["10.1161\/JAHA.125.048672"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.048672","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"2025-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e048672"}}