{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:15:17Z","timestamp":1773148517603,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mamm Genome"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1007\/s00335-025-10135-x","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T15:49:05Z","timestamp":1747410545000},"page":"859-871","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic and immune landscape of keratoconus: insights from Mendelian randomization analysis"],"prefix":"10.1007","volume":"36","author":[{"given":"Yuhui","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4294-3136","authenticated-orcid":false,"given":"Yanchun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"issue":"9","key":"10135_CR8","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/mp.2012.37","volume":"17","author":"M Ayalew","year":"2012","unstructured":"Ayalew M, Le-Niculescu H, Levey DF, Jain N, Changala B, Patel SD, Winiger E, Breier A, Shekhar A, Amdur R et al (2012) Convergent functional genomics of schizophrenia: from comprehensive Understanding to genetic risk prediction. Mol Psychiatry 17(9):887\u2013905","journal-title":"Mol Psychiatry"},{"issue":"11","key":"10135_CR17","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.1016\/j.jmb.2016.04.028","volume":"428","author":"B Bragantini","year":"2016","unstructured":"Bragantini B, Tiotiu D, Rothe B, Saliou JM, Marty H, Cianferani S, Charpentier B, Quinternet M, Manival X (2016) Functional and structural insights of the Zinc-Finger HIT protein family members involved in box C\/D SnoRNP biogenesis. J Mol Biol 428(11):2488\u20132506","journal-title":"J Mol Biol"},{"key":"10135_CR6","doi-asserted-by":"publisher","first-page":"108398","DOI":"10.1016\/j.exer.2020.108398","volume":"202","author":"Y Bykhovskaya","year":"2021","unstructured":"Bykhovskaya Y, Rabinowitz YS (2021) Update on the genetics of keratoconus. Exp Eye Res 202:108398","journal-title":"Exp Eye Res"},{"issue":"5\u20136","key":"10135_CR5","doi-asserted-by":"publisher","first-page":"275","DOI":"10.3109\/08820538.2013.825295","volume":"28","author":"HY Chang","year":"2013","unstructured":"Chang HY, Chodosh J (2013) The genetics of keratoconus. Semin Ophthalmol 28(5\u20136):275\u2013280","journal-title":"Semin Ophthalmol"},{"key":"10135_CR16","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/978-1-4939-7493-1_12","volume":"1711","author":"B Chen","year":"2018","unstructured":"Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA (2018) Profiling tumor infiltrating immune cells with CIBERSORT. Methods Mol Biol 1711:243\u2013259","journal-title":"Methods Mol Biol"},{"issue":"1","key":"10135_CR31","doi-asserted-by":"publisher","first-page":"20891","DOI":"10.1038\/s41598-021-99805-9","volume":"11","author":"S D\u2019Souza","year":"2021","unstructured":"D\u2019Souza S, Nair AP, Sahu GR, Vaidya T, Shetty R, Khamar P, Mullick R, Gupta S, Dickman MM, Nuijts R et al (2021) Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile. Sci Rep 11(1):20891","journal-title":"Sci Rep"},{"issue":"2","key":"10135_CR2","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/eye.2013.278","volume":"28","author":"AE Davidson","year":"2014","unstructured":"Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ (2014) The pathogenesis of keratoconus. Eye (Lond) 28(2):189\u2013195","journal-title":"Eye (Lond)"},{"issue":"5","key":"10135_CR9","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.ajhg.2013.03.022","volume":"92","author":"X He","year":"2013","unstructured":"He X, Fuller CK, Song Y, Meng Q, Zhang B, Yang X, Li H (2013) Sherlock: detecting gene-disease associations by matching patterns of expression QTL and GWAS. Am J Hum Genet 92(5):667\u2013680","journal-title":"Am J Hum Genet"},{"issue":"12","key":"10135_CR30","doi-asserted-by":"publisher","first-page":"1786","DOI":"10.1038\/s41588-022-01208-7","volume":"54","author":"H Holstege","year":"2022","unstructured":"Holstege H, Hulsman M, Charbonnier C, Grenier-Boley B, Quenez O, Grozeva D, van Rooij JGJ, Sims R, Ahmad S, Amin N et al (2022) Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer\u2019s disease. Nat Genet 54(12):1786\u20131794","journal-title":"Nat Genet"},{"key":"10135_CR13","doi-asserted-by":"crossref","unstructured":"Huang W, Xiao J, Ji J, Chen L (2021) Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study. Elife 10","DOI":"10.7554\/eLife.73873"},{"issue":"1","key":"10135_CR7","first-page":"37","volume":"37","author":"JA Karolak","year":"2016","unstructured":"Karolak JA, Polakowski P, Szaflik J, Szaflik JP, Gajecka M (2016) Molecular screening of keratoconus susceptibility sequence variants in VSX1, TGFBI, DOCK9, STK24, and IPO5 genes in Polish patients and novel TGFBI variant identification. Ophthalmic Genet 37(1):37\u201343","journal-title":"Ophthalmic Genet"},{"issue":"7","key":"10135_CR21","first-page":"1773","volume":"54","author":"D Kitamura","year":"1996","unstructured":"Kitamura D (1996) Function of HS1 protein in B-cell antigen-receptor signaling and induction of apoptosis. Nihon Rinsho 54(7):1773\u20131778","journal-title":"Nihon Rinsho"},{"key":"10135_CR28","doi-asserted-by":"publisher","first-page":"1058834","DOI":"10.3389\/fcvm.2023.1058834","volume":"10","author":"X Kong","year":"2023","unstructured":"Kong X, Sun H, Wei K, Meng L, Lv X, Liu C, Lin F, Gu X (2023) WGCNA combined with machine learning algorithms for analyzing key genes and immune cell infiltration in heart failure due to ischemic cardiomyopathy. Front Cardiovasc Med 10:1058834","journal-title":"Front Cardiovasc Med"},{"issue":"2","key":"10135_CR3","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00347-021-01460-y","volume":"119","author":"SJ Lang","year":"2022","unstructured":"Lang SJ, Maier P, Bohringer T, Reinhard T (2022) Early diagnosis of keratoconus. Ophthalmologe 119(2):209\u2013218","journal-title":"Ophthalmologe"},{"issue":"3","key":"10135_CR35","first-page":"2703","volume":"16","author":"Q Luo","year":"2018","unstructured":"Luo Q, Xiao P, Li X, Deng Z, Qing C, Su R, Xu J, Guo Y, Huang Z, Li J (2018) Overexpression of CD64 on CD14(++)CD16(-) and CD14(++)CD16(+) monocytes of rheumatoid arthritis patients correlates with disease activity. Exp Ther Med 16(3):2703\u20132711","journal-title":"Exp Ther Med"},{"issue":"4","key":"10135_CR4","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.optom.2019.11.001","volume":"13","author":"LE Masiwa","year":"2020","unstructured":"Masiwa LE, Moodley V (2020) A review of corneal imaging methods for the early diagnosis of pre-clinical keratoconus. J Optom 13(4):269\u2013275","journal-title":"J Optom"},{"issue":"10","key":"10135_CR36","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1016\/j.transproceed.2011.10.040","volume":"43","author":"N Naderi","year":"2011","unstructured":"Naderi N, Moazzeni SM, Pourfathollah AA, Alimoghaddam K (2011) High expression of Fas ligand on cord blood dendritic cells: a possible immunoregulatory mechanism after cord blood transplantation. Transpl Proc 43(10):3913\u20133919","journal-title":"Transpl Proc"},{"issue":"23","key":"10135_CR18","doi-asserted-by":"publisher","first-page":"6202","DOI":"10.1182\/blood-2010-06-292243","volume":"117","author":"P Neri","year":"2011","unstructured":"Neri P, Ren L, Azab AK, Brentnall M, Gratton K, Klimowicz AC, Lin C, Duggan P, Tassone P, Mansoor A et al (2011) Integrin beta7-mediated regulation of multiple myeloma cell adhesion, migration, and invasion. Blood 117(23):6202\u20136213","journal-title":"Blood"},{"key":"10135_CR32","doi-asserted-by":"publisher","first-page":"1220646","DOI":"10.3389\/fimmu.2023.1220646","volume":"14","author":"X Niu","year":"2023","unstructured":"Niu X, Xu M, Zhu J, Zhang S, Yang Y (2023) Identification of the immune-associated characteristics and predictive biomarkers of keratoconus based on single-cell RNA-sequencing and bulk RNA-sequencing. Front Immunol 14:1220646","journal-title":"Front Immunol"},{"key":"10135_CR22","doi-asserted-by":"publisher","first-page":"751875","DOI":"10.3389\/fonc.2021.751875","volume":"11","author":"Y Nurzat","year":"2021","unstructured":"Nurzat Y, Su W, Min P, Li K, Xu H, Zhang Y (2021) Identification of therapeutic targets and prognostic biomarkers among integrin subunits in the skin cutaneous melanoma microenvironment. Front Oncol 11:751875","journal-title":"Front Oncol"},{"issue":"10","key":"10135_CR15","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1038\/s41588-020-0684-4","volume":"52","author":"V Orru","year":"2020","unstructured":"Orru V, Steri M, Sidore C, Marongiu M, Serra V, Olla S, Sole G, Lai S, Dei M, Mulas A et al (2020) Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet 52(10):1036\u20131045","journal-title":"Nat Genet"},{"issue":"1","key":"10135_CR23","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s00401-024-02694-1","volume":"147","author":"T Redmer","year":"2024","unstructured":"Redmer T, Schumann E, Peters K, Weidemeier ME, Nowak S, Schroeder HWS, Vidal A, Radbruch H, Lehmann A, Kreuzer-Redmer S et al (2024) MET receptor serves as a promising target in melanoma brain metastases. Acta Neuropathol 147(1):44","journal-title":"Acta Neuropathol"},{"key":"10135_CR37","first-page":"47","volume":"410","author":"K Sato","year":"2017","unstructured":"Sato K, Uto T, Fukaya T, Takagi H (2017) Regulatory dendritic cells. Curr Top Microbiol Immunol 410:47\u201371","journal-title":"Curr Top Microbiol Immunol"},{"issue":"7","key":"10135_CR10","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/ng1589","volume":"37","author":"EE Schadt","year":"2005","unstructured":"Schadt EE, Lamb J, Yang X, Zhu J, Edwards S, Guhathakurta D, Sieberts SK, Monks S, Reitman M, Zhang C et al (2005) An integrative genomics approach to infer causal associations between gene expression and disease. Nat Genet 37(7):710\u2013717","journal-title":"Nat Genet"},{"issue":"8","key":"10135_CR25","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1093\/hmg\/ddab075","volume":"30","author":"V Shinde","year":"2021","unstructured":"Shinde V, Sobreira N, Wohler ES, Maiti G, Hu N, Silvestri G, George S, Jackson J, Chakravarti A, Willoughby CE et al (2021) Pathogenic alleles in microtubule, secretory granule and extracellular matrix-related genes in Familial keratoconus. Hum Mol Genet 30(8):658\u2013671","journal-title":"Hum Mol Genet"},{"issue":"17\u201318","key":"10135_CR38","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1016\/j.cca.2011.11.006","volume":"413","author":"M Shipkova","year":"2012","unstructured":"Shipkova M, Wieland E (2012) Surface markers of lymphocyte activation and markers of cell proliferation. Clin Chim Acta 413(17\u201318):1338\u20131349","journal-title":"Clin Chim Acta"},{"issue":"6","key":"10135_CR34","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1002\/eji.200838603","volume":"39","author":"DK Sojka","year":"2009","unstructured":"Sojka DK, Hughson A, Fowell DJ (2009) CTLA-4 is required by CD4\u2009+\u2009CD25\u2009+\u2009Treg to control CD4\u2009+\u2009T-cell lymphopenia-induced proliferation. Eur J Immunol 39(6):1544\u20131551","journal-title":"Eur J Immunol"},{"key":"10135_CR33","doi-asserted-by":"publisher","first-page":"782709","DOI":"10.3389\/fgene.2022.782709","volume":"13","author":"X Sun","year":"2022","unstructured":"Sun X, Zhang H, Shan M, Dong Y, Zhang L, Chen L, Wang Y (2022) Comprehensive transcriptome analysis of patients with keratoconus highlights the regulation of immune responses and inflammatory processes. Front Genet 13:782709","journal-title":"Front Genet"},{"issue":"6","key":"10135_CR19","doi-asserted-by":"publisher","first-page":"e0251272","DOI":"10.1371\/journal.pone.0251272","volume":"16","author":"Y Takashima","year":"2021","unstructured":"Takashima Y, Kawaguchi A, Fukai J, Iwadate Y, Kajiwara K, Hondoh H, Yamanaka R (2021) Survival prediction based on the gene expression associated with cancer morphology and microenvironment in primary central nervous system lymphoma. PLoS ONE 16(6):e0251272","journal-title":"PLoS ONE"},{"issue":"9","key":"10135_CR14","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","volume":"53","author":"U Vosa","year":"2021","unstructured":"Vosa U, Claringbould A, Westra HJ, Bonder MJ, Deelen P, Zeng B, Kirsten H, Saha A, Kreuzhuber R, Yazar S et al (2021) Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet 53(9):1300\u20131310","journal-title":"Nat Genet"},{"key":"10135_CR20","doi-asserted-by":"crossref","unstructured":"Wakula M, Balcerak A, Rubel T, Chmielarczyk M, Konopinski R, Lyczek F, Grzybowska EA (2020) The interactome of multifunctional HAX1 protein suggests its role in the regulation of energy metabolism, de-aggregation, cytoskeleton organization and RNA-processing. Biosci Rep 40(11)","DOI":"10.1042\/BSR20203094"},{"issue":"4","key":"10135_CR26","first-page":"311","volume":"115","author":"KA Wojcik","year":"2013","unstructured":"Wojcik KA, Blasiak J, Kurowska AK, Szaflik J, Szaflik JP (2013) Oxidative stress in the pathogenesis of keratoconus. Klin Oczna 115(4):311\u2013316","journal-title":"Klin Oczna"},{"issue":"1","key":"10135_CR1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.18388\/abp.2014_1923","volume":"61","author":"KA Wojcik","year":"2014","unstructured":"Wojcik KA, Blasiak J, Szaflik J, Szaflik JP (2014) Role of biochemical factors in the pathogenesis of keratoconus. Acta Biochim Pol 61(1):55\u201362","journal-title":"Acta Biochim Pol"},{"key":"10135_CR27","doi-asserted-by":"publisher","first-page":"109342","DOI":"10.1016\/j.exer.2022.109342","volume":"226","author":"L Xu","year":"2023","unstructured":"Xu L, Yang K, Zhu M, Yin S, Gu Y, Fan Q, Wang Y, Pang C, Ren S (2023) Trio-based exome sequencing broaden the genetic spectrum in keratoconus. Exp Eye Res 226:109342","journal-title":"Exp Eye Res"},{"issue":"8","key":"10135_CR24","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1158\/2326-6066.CIR-20-0879","volume":"9","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Xie R, Zhang H, Zheng Y, Lin C, Yang L, Huang M, Li M, Song F, Lu L et al (2021) Integrin beta7 inhibits colorectal Cancer pathogenesis via maintaining antitumor immunity. Cancer Immunol Res 9(8):967\u2013980","journal-title":"Cancer Immunol Res"},{"issue":"19","key":"10135_CR29","doi-asserted-by":"publisher","first-page":"7926","DOI":"10.18632\/aging.204323","volume":"14","author":"Z Zhao","year":"2022","unstructured":"Zhao Z, Liu M, Xu Z, Cai Y, Peng B, Liang Q, Yan Y, Liu W, Kang F, He Q et al (2022) Identification of ACSF gene family as therapeutic targets and immune-associated biomarkers in hepatocellular carcinoma. Aging 14(19):7926\u20137940","journal-title":"Aging"},{"issue":"4","key":"10135_CR12","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1007\/s40471-017-0128-6","volume":"4","author":"J Zheng","year":"2017","unstructured":"Zheng J, Baird D, Borges MC, Bowden J, Hemani G, Haycock P, Evans DM, Smith GD (2017) Recent developments in Mendelian randomization studies. Curr Epidemiol Rep 4(4):330\u2013345","journal-title":"Curr Epidemiol Rep"},{"issue":"5","key":"10135_CR11","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ng.3538","volume":"48","author":"Z Zhu","year":"2016","unstructured":"Zhu Z, Zhang F, Hu H, Bakshi A, Robinson MR, Powell JE, Montgomery GW, Goddard ME, Wray NR, Visscher PM et al (2016) Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat Genet 48(5):481\u2013487","journal-title":"Nat Genet"}],"container-title":["Mammalian Genome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00335-025-10135-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00335-025-10135-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00335-025-10135-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T18:36:11Z","timestamp":1756924571000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00335-025-10135-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10135"],"URL":"https:\/\/doi.org\/10.1007\/s00335-025-10135-x","relation":{},"ISSN":["0938-8990","1432-1777"],"issn-type":[{"value":"0938-8990","type":"print"},{"value":"1432-1777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]},"assertion":[{"value":"13 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors have agreed to publish this research article in your journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}