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Genome-wide association study (GWAS) data for cortical surface area (SAw\/nw) and thickness (THw\/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (<jats:italic>p<\/jats:italic>\u2009=\u2009.0342, beta (se)\u2009=\u20095.7127 (2.6969)), parahippocampal SAw (<jats:italic>p<\/jats:italic>\u2009=\u2009.0224, beta (se)\u2009=\u20091.5577 (0.6822)), rostral middle frontal SAw (<jats:italic>p<\/jats:italic>\u2009=\u2009.0154, beta (se)\u2009=\u2009\u2212\u00a09.0301 (3.7281)), cuneus THw (<jats:italic>p<\/jats:italic>\u2009=\u2009.0418, beta (se)\u2009=\u2009 \u2212\u00a00.0020 (0.0010)), lateral orbitofrontal THw (<jats:italic>p<\/jats:italic>\u2009=\u2009.0281, beta (se)\u2009=\u20090.0025 (0.0010)), and lateral orbitofrontal THnw (<jats:italic>p<\/jats:italic>\u2009=\u2009.0417, beta (se)\u2009=\u20090.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-024-04892-7","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T15:01:47Z","timestamp":1705762907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study"],"prefix":"10.1186","volume":"22","author":[{"given":"Dongren","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7637-1305","authenticated-orcid":false,"given":"Hongyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,20]]},"reference":[{"key":"4892_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2020.100889","volume":"60","author":"M Sparaco","year":"2021","unstructured":"Sparaco M, Bonavita S. 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