{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:12:49Z","timestamp":1780791169594,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Preclinical and epidemiological studies suggest that proprotein convertase subtilisin\/kexin type 9 (PCSK9) had a potential effect on the development of SLE, but it was unclear whether a causal relationship exists. We aimed to investigate the association between genetically proxied inhibition of PCSK9 and the risk of SLE using a two\u2010sample Mendelian randomization (MR) approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Single nucleotide polymorphisms (SNPs) associated with PCSK9 were extracted from pooled data obtained from the Global Lipid Genetics Consortium (GLGC) Genome\u2010wide Association Study (GWAS) related to LDL\u2010c levels, which was used as a proxy for PCSK9 inhibition. Pooled statistics for SLE were obtained from an independent GWAS dataset including 5201 SLE patients and 9066 controls. Inverse variance\u2010weighted random\u2010effects models were used to examine the association between genetically proxied inhibition of PCSK9 and the risk of SLE. MR\u2010Egger, weighted median, weighted mode, Simple mode, and co\u2010location analyses were used as sensitivity analyses to test the robustness of the analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically proxied inhibition of PCSK9 was associated with a reduced risk of SLE (OR\u2009=\u20090.51, 95% CI\u2009=\u20090.34 to 0.77, <jats:italic>p<\/jats:italic>\u2009=\u2009.001). This finding was replicated in an earlier GLGC GWAS analysis (OR\u2009=\u20090.59, 95% CI\u2009=\u20090.40 to 0.87, <jats:italic>p<\/jats:italic>\u2009=\u2009.007). Sensitivity analysis ensured that the results were robust. Co\u2010localization analysis did not find evidence of shared causal variation between PCSK9 and SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This Mendelian randomization study showed that PCSK9 was associated with SLE pathogenesis, and its inhibition was associated with a reduced risk of SLE. This study has offered a prospective therapeutic avenue for intervening in the progression of SLE by inhibiting PCSK9 levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.15106","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T13:49:36Z","timestamp":1712152176000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Association between genetically proxied <scp>PCSK9<\/scp> inhibition and systemic lupus erythematosus risk: A mendelian randomization study"],"prefix":"10.1111","volume":"27","author":[{"given":"Xincan","family":"Ji","sequence":"first","affiliation":[{"name":"School of Public Health Wannan Medical College  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010Yang","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Public Health Wannan Medical College  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Han","sequence":"additional","affiliation":[{"name":"School of Public Health Wannan Medical College  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Science and Technology Department The First Affiliated Hospital of Wannan Medical College  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0555-0119","authenticated-orcid":false,"given":"Hui","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Public Health Wannan Medical College  Wuhu Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102861"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667097"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.974826"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2020-001247"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107466"},{"issue":"5","key":"e_1_2_11_7_1","first-page":"709","article-title":"The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population\u2010based cohort study","volume":"56","author":"Hermansen M\u2010L","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0110-5"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.020912"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0428-z"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-017-0619-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2022.2017281"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1346"},{"issue":"4","key":"e_1_2_11_14_1","article-title":"Mendelian randomization","volume":"12","author":"Birney E","year":"2022","journal-title":"Cold Spring Harb Perspect Med"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2022.6051"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04064-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-022-01508-0"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12111551"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15393"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3434"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003897"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1017444"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4152-9"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7414.557"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2797"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.0150"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"issue":"159","key":"e_1_2_11_33_1","first-page":"49","article-title":"Role of dyslipidemia in accelerating inflammation, autoimmunity, and atherosclerosis in systemic lupus erythematosus and other autoimmune diseases","volume":"30","author":"Wang Y","year":"2020","journal-title":"Discov Med"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-016-8892-9"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.11.04"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203320926253"},{"key":"e_1_2_11_37_1","first-page":"859","article-title":"Effects of interfering with PCSK9 expression on immune function in lupus mice","volume":"2020","author":"Luo T","year":"2020","journal-title":"Mianyixue Zazhi"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.05.004"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102856"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.15106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T12:37:00Z","timestamp":1714135020000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.15106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1111\/1756-185X.15106"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.15106","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-10-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15106"}}