{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:39:09Z","timestamp":1791308349900,"version":"4.3.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T00:00:00Z","timestamp":1728518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202311012"],"award-info":[{"award-number":["SZSM202311012"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20230807114605011"],"award-info":[{"award-number":["JCYJ20230807114605011"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-024-74455-9","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T09:01:51Z","timestamp":1728550911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mendelian randomization reveals that abnormal lipid metabolism mediates the causal relationship between body mass index and keratoconus"],"prefix":"10.1038","volume":"14","author":[{"given":"Jiaoman","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicheng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhao","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"74455_CR1","doi-asserted-by":"publisher","first-page":"101559","DOI":"10.1016\/j.clae.2021.101559","volume":"45","author":"G Santodomingo-Rubido, Carracedo","year":"2022","unstructured":"Santodomingo-Rubido, Carracedo, G., Suzaki, A., Villa-Collar, C., Vincent, S. J. & Wolffsohn, J. S. Keratoconus: an updated review. Cont. Lens Anterior Eye. 45, 101559. https:\/\/doi.org\/10.1016\/j.clae.2021.101559 (2022).","journal-title":"Cont. Lens Anterior Eye"},{"key":"74455_CR2","doi-asserted-by":"publisher","first-page":"1212314","DOI":"10.3389\/fmed.2023.1212314","volume":"10","author":"R Deshmukh","year":"2023","unstructured":"Deshmukh, R. et al. Management of keratoconus: an updated review. Front. Med. (Lausanne). 10, 1212314. https:\/\/doi.org\/10.3389\/fmed.2023.1212314 (2023).","journal-title":"Front. Med. (Lausanne)"},{"key":"74455_CR3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41421-022-00397-z","volume":"8","author":"S Dou","year":"2022","unstructured":"Dou, S. et al. Single-cell atlas of keratoconus corneas revealed aberrant transcriptional signatures and implicated mechanical stretch as a trigger for keratoconus pathogenesis. Cell. Discov. 8, 66. https:\/\/doi.org\/10.1038\/s41421-022-00397-z (2022).","journal-title":"Cell. Discov"},{"key":"74455_CR4","doi-asserted-by":"publisher","first-page":"108734","DOI":"10.1016\/j.exer.2021.108734","volume":"211","author":"ALD Teh","year":"2021","unstructured":"Teh, A. L. D., Jayapalan, J. J., Loke, M. F., Kadir, A. J. W. A. & Subrayan, V. Identification of potential serum metabolic biomarkers for patient with keratoconus using untargeted metabolomics approach. Exp. Eye Res. 211, 108734. https:\/\/doi.org\/10.1016\/j.exer.2021.108734 (2021).","journal-title":"Exp. Eye Res."},{"key":"74455_CR5","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1194\/jlr.M067264","volume":"58","author":"H Qi","year":"2017","unstructured":"Qi, H. et al. Analysis of sphingolipids in human corneal fibroblasts from normal and keratoconus patients. J. Lipid Res. 58, 636\u2013648. https:\/\/doi.org\/10.1194\/jlr.M067264 (2017).","journal-title":"J. Lipid Res."},{"key":"74455_CR6","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. et al. Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile. Sci. Rep. 11, 20891. https:\/\/doi.org\/10.1038\/s41598-021-99805-9 (2021).","journal-title":"Sci. Rep."},{"key":"74455_CR7","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1136\/bjo.2008.144253","volume":"93","author":"IL Lema","year":"2009","unstructured":"Lema, I. L., Sobrino, T., Dur\u00e1n, J. A., Brea, D. & D\u00edez-Feijoo, E. Subclinical keratoconus and inflammatory molecules from tears. Br. J. Ophthalmol. 93, 820\u2013824. https:\/\/doi.org\/10.1136\/bjo.2008.144253 (2009).","journal-title":"Br. J. Ophthalmol."},{"key":"74455_CR8","doi-asserted-by":"publisher","first-page":"10862","DOI":"10.1038\/s41598-023-37472-8","volume":"13","author":"J Pinheiro-Costa","year":"2023","unstructured":"Pinheiro-Costa, J. et al. Serum inflammatory biomarkers are associated with increased choroidal thickness in keratoconus. Sci. Rep. 13, 10862. https:\/\/doi.org\/10.1038\/s41598-023-37472-8 (2023).","journal-title":"Sci. Rep."},{"key":"74455_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exer.2015.01.007","volume":"132","author":"D Karamichos","year":"2015","unstructured":"Karamichos, D. et al. Tear metabolite changes in keratoconus. Exp. Eye Res. 132, 1\u20138. https:\/\/doi.org\/10.1016\/j.exer.2015.01.007 (2015).","journal-title":"Exp. Eye Res."},{"key":"74455_CR10","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/ajcn\/47.3.553","volume":"47","author":"JS Garrow","year":"1988","unstructured":"Garrow, J. S. Three limitations of body mass index. Am. J. Clin. Nutr. 47, 553. https:\/\/doi.org\/10.1093\/ajcn\/47.3.553 (1988).","journal-title":"Am. J. Clin. Nutr."},{"key":"74455_CR11","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/s41366-023-01281-w","volume":"47","author":"V-P M\u00e4kinen","year":"2023","unstructured":"M\u00e4kinen, V-P. et al. Longitudinal metabolomics of increasing body-mass index and waist-hip ratio reveals two dynamic patterns of obesity pandemic. Int. J. Obes. (Lond). 47, 453\u2013462. https:\/\/doi.org\/10.1038\/s41366-023-01281-w (2023).","journal-title":"Int. J. Obes. (Lond)"},{"key":"74455_CR12","doi-asserted-by":"publisher","first-page":"3137","DOI":"10.1021\/acs.jproteome.6b01062","volume":"16","author":"M Carayol","year":"2017","unstructured":"Carayol, M. et al. Blood metabolic signatures of body Mass Index: a targeted Metabolomics Study in the EPIC Cohort. J. Proteome Res. 16, 3137\u20133146. https:\/\/doi.org\/10.1021\/acs.jproteome.6b01062 (2017).","journal-title":"J. Proteome Res."},{"key":"74455_CR13","doi-asserted-by":"publisher","first-page":"4214","DOI":"10.1038\/s41467-023-39919-y","volume":"14","author":"KM Garske","year":"2023","unstructured":"Garske, K. M. et al. Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes. Nat. Commun. 14, 4214. https:\/\/doi.org\/10.1038\/s41467-023-39919-y (2023).","journal-title":"Nat. Commun."},{"key":"74455_CR14","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.120.316101","volume":"126","author":"M-E Pich\u00e9","year":"2020","unstructured":"Pich\u00e9, M-E., Tchernof, A. & Despr\u00e9s, J-P. Obesity phenotypes, diabetes, and Cardiovascular diseases. Circ. Res. 126, 1477\u20131500. https:\/\/doi.org\/10.1161\/CIRCRESAHA.120.316101 (2020).","journal-title":"Circ. Res."},{"key":"74455_CR15","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1097\/ICO.0b013e318281e755","volume":"32","author":"MS Pihlblad","year":"2013","unstructured":"Pihlblad, M. S. & Schaefer, D. P. Eyelid laxity, obesity, and obstructive sleep apnea in keratoconus. Cornea. 32, 1232\u20131236. https:\/\/doi.org\/10.1097\/ICO.0b013e318281e755 (2013).","journal-title":"Cornea"},{"key":"74455_CR16","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.ajo.2020.11.021","volume":"224","author":"E Eliasi","year":"2021","unstructured":"Eliasi, E. et al. The Association between Keratoconus and Body Mass Index: a Population-based cross-sectional study among half a million adolescents. Am. J. Ophthalmol. 224, 200\u2013206. https:\/\/doi.org\/10.1016\/j.ajo.2020.11.021 (2021).","journal-title":"Am. J. Ophthalmol."},{"key":"74455_CR17","doi-asserted-by":"publisher","unstructured":"Ren, S. et al. A high body mass index strengthens the association between the time of eye rubbing and keratoconus in a Chinese population: a case-control study. BMC Public Health.23, 2032.\u00a0https:\/\/doi.org\/10.1186\/s12889-023-16937-5 (2023).","DOI":"10.1186\/s12889-023-16937-5"},{"key":"74455_CR18","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/ASN.2016010098","volume":"27","author":"P Sekula","year":"2016","unstructured":"Sekula, P., Del Greco, M. F., Pattaro, C. & K\u00f6ttgen, A. Mendelian randomization as an Approach to assess causality using Observational Data. J. Am. Soc. Nephrol. 27, 3253\u20133265. https:\/\/doi.org\/10.1681\/ASN.2016010098 (2016).","journal-title":"J. Am. Soc. Nephrol."},{"key":"74455_CR19","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1037\/hea0000775","volume":"38","author":"EL Kacel","year":"2019","unstructured":"Kacel, E. L. et al. Interleukin-6 and body mass index, tobacco use, and sleep in gynecologic cancers. Health Psychol. 38, 866\u2013877. https:\/\/doi.org\/10.1037\/hea0000775 (2019).","journal-title":"Health Psychol."},{"key":"74455_CR20","doi-asserted-by":"publisher","first-page":"118191","DOI":"10.1016\/j.lfs.2020.118191","volume":"259","author":"CP Vieira","year":"2020","unstructured":"Vieira, C. P. et al. Role of metalloproteinases and TNF-\u03b1 in obesity-associated asthma in mice. Life Sci. 259, 118191. https:\/\/doi.org\/10.1016\/j.lfs.2020.118191 (2020).","journal-title":"Life Sci."},{"key":"74455_CR21","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1111\/eci.12649","volume":"46","author":"A Lauhio","year":"2016","unstructured":"Lauhio, A. et al. Association of MMP-8 with obesity, smoking, and insulin resistance. Eur. J. Clin. Invest. 46, 757\u2013765. https:\/\/doi.org\/10.1111\/eci.12649 (2016).","journal-title":"Eur. J. Clin. Invest."},{"key":"74455_CR22","doi-asserted-by":"publisher","first-page":"eaah6324","DOI":"10.1126\/scitranslmed.aah6324","volume":"10","author":"R Mazor","year":"2018","unstructured":"Mazor, R. et al. Cleavage of the leptin receptor by matrix metalloproteinase-2 promotes leptin resistance and obesity in mice. Sci. Transl Med. 10, eaah6324. https:\/\/doi.org\/10.1126\/scitranslmed.aah6324 (2018).","journal-title":"Sci. Transl Med."},{"key":"74455_CR23","doi-asserted-by":"publisher","first-page":"988","DOI":"10.3389\/fimmu.2019.00988","volume":"10","author":"D Bastian","year":"2019","unstructured":"Bastian, D., Wu, Y., Betts, B. C. & Yu, X-Z. The IL-12 cytokine and receptor family in Graft-vs.-Host disease. Front. Immunol. 10, 988. https:\/\/doi.org\/10.3389\/fimmu.2019.00988 (2019).","journal-title":"Front. Immunol."},{"key":"74455_CR24","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.4049\/jimmunol.159.8.4094","volume":"159","author":"LA Joosten","year":"1997","unstructured":"Joosten, L. A., Lubberts, E., Helsen, M. M. & van den Berg, W. B. Dual role of IL-12 in early and late stages of murine collagen type II arthritis. J. Immunol. 159, 4094\u20134102 (1997).","journal-title":"J. Immunol."},{"key":"74455_CR25","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.4049\/jimmunol.1000425","volume":"185","author":"Y Park","year":"2010","unstructured":"Park, Y. et al. IL-12p35 promotes antibody-induced joint inflammation by activating NKT cells and suppressing TGF-beta. J. Immunol. 185, 1476\u20131484. https:\/\/doi.org\/10.4049\/jimmunol.1000425 (2010).","journal-title":"J. Immunol."},{"key":"74455_CR26","doi-asserted-by":"publisher","first-page":"O1","DOI":"10.1111\/ceo.14215","volume":"51","author":"I Seth","year":"2023","unstructured":"Seth, I. et al. The association between keratoconus and allergic eye diseases: a systematic review and meta-analysis. Clin. Exp. Ophthalmol. 51, O1\u2013O16. https:\/\/doi.org\/10.1111\/ceo.14215 (2023).","journal-title":"Clin. Exp. Ophthalmol."},{"key":"74455_CR27","doi-asserted-by":"publisher","first-page":"e16437","DOI":"10.1371\/journal.pone.0016437","volume":"6","author":"AS Jun","year":"2011","unstructured":"Jun, A. S. et al. Subnormal cytokine profile in the tear fluid of keratoconus patients. PLoS One. 6, e16437. https:\/\/doi.org\/10.1371\/journal.pone.0016437 (2011).","journal-title":"PLoS One"},{"key":"74455_CR28","doi-asserted-by":"publisher","first-page":"108594","DOI":"10.1016\/j.exer.2021.108594","volume":"207","author":"SE Wilson","year":"2021","unstructured":"Wilson, S. E. TGF beta \u2013\u20091, -2, and \u2013\u20093 in the modulation of fibrosis in the cornea and other organs. Exp. Eye Res. 207, 108594. https:\/\/doi.org\/10.1016\/j.exer.2021.108594 (2021).","journal-title":"Exp. Eye Res."},{"key":"74455_CR29","doi-asserted-by":"publisher","first-page":"7526","DOI":"10.1074\/jbc.M111.308825","volume":"287","author":"J Barnes","year":"2012","unstructured":"Barnes, J., Warejcka, D., Simpliciano, J., Twining, S. & Steet, R. Latency-associated peptide of transforming growth factor-\u03b21 is not subject to physiological mannose phosphorylation. J. Biol. Chem. 287, 7526\u20137534. https:\/\/doi.org\/10.1074\/jbc.M111.308825 (2012).","journal-title":"J. Biol. Chem."},{"key":"74455_CR30","doi-asserted-by":"publisher","first-page":"e2303075120","DOI":"10.1073\/pnas.2303075120","volume":"120","author":"Y Wu","year":"2023","unstructured":"Wu, Y. et al. FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation. Proc. Natl. Acad. Sci. U S A. 120, e2303075120. https:\/\/doi.org\/10.1073\/pnas.2303075120 (2023).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"issue":"5","key":"74455_CR31","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1194\/jlr.R001347","volume":"51","author":"S Kenchegowda","year":"2010","unstructured":"Kenchegowda, S. & Bazan, H. E. Significance of lipid mediators in corneal injury and repair. J. Lipid Res. 51 (5), 879\u2013891. https:\/\/doi.org\/10.1194\/jlr.R001347 (2010).","journal-title":"J. Lipid Res."},{"key":"74455_CR32","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.3390\/molecules25122933","volume":"25","author":"A Wojakowska","year":"2020","unstructured":"Wojakowska, A. et al. Metabolomic signature discriminates normal human cornea from keratoconus\u2014a pilot GC\/MS study. Molecules 25, 2933. https:\/\/doi.org\/10.3390\/molecules25122933 (2020).","journal-title":"Molecules"},{"key":"74455_CR33","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1177\/11206721211000644","volume":"32","author":"R Oltulu","year":"2022","unstructured":"Oltulu, R., Katipo\u011flu, Z., G\u00fcndo\u011fan, A. O., Mirza, E. & Belviranl\u0131, S. Evaluation of inflammatory biomarkers in patients with keratoconus. Eur. J. Ophthalmol. 32, 154\u2013159. https:\/\/doi.org\/10.1177\/11206721211000644 (2022).","journal-title":"Eur. J. Ophthalmol."},{"key":"74455_CR34","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s12886-023-02934-0","volume":"23","author":"S Mohaghegh","year":"2023","unstructured":"Mohaghegh, S. et al. Prevalence and risk factors of keratoconus (including oxidative stress biomarkers) in a cohort study of Shiraz University of Medical Science employees in Iran. BMC Ophthalmol. 23, 188. https:\/\/doi.org\/10.1186\/s12886-023-02934-0 (2023).","journal-title":"BMC Ophthalmol."},{"key":"74455_CR35","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.tplants.2017.09.002","volume":"22","author":"Y Nakamura","year":"2017","unstructured":"Nakamura, Y. Plant Phospholipid Diversity: emerging functions in metabolism and protein-lipid interactions. Trends Plant. Sci. 22, 1027\u20131040. https:\/\/doi.org\/10.1016\/j.tplants.2017.09.002 (2017).","journal-title":"Trends Plant. Sci."},{"key":"74455_CR36","doi-asserted-by":"publisher","unstructured":"Rajala, A., McCauley, A., Brush, R. S., Nguyen, K. & Rajala, R. V. S. Phosphoinositide lipids in ocular tissues. Biology (Basel). 9, 125.\u00a0https:\/\/doi.org\/10.3390\/biology9060125 (2020).","DOI":"10.3390\/biology9060125"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74455-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74455-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74455-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,13]],"date-time":"2024-10-13T13:01:47Z","timestamp":1728824507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-74455-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,10]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["74455"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-74455-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,10]]},"assertion":[{"value":"7 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23698"}}