{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:49:31Z","timestamp":1793332171006,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07\u20131.55,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5\u20137%, lowest risk quartile) to 41% (95%CI 33\u201349%, highest risk quartile). The model replicated across two cohorts (Geisinger, USA, and FinnGen, Finland). This study indicates that a combined model might enhance individual MS risk stratification, paving the way for precision-based ON treatment and earlier MS disease-modifying therapy.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-44917-9","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T06:02:12Z","timestamp":1709100132000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9701-0234","authenticated-orcid":false,"given":"Pavel","family":"Loginovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8179-488X","authenticated-orcid":false,"given":"Feiyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7006-1285","authenticated-orcid":false,"given":"Jiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3166-9685","authenticated-orcid":false,"given":"Lauric","family":"Ferrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-5451","authenticated-orcid":false,"given":"Uyenlinh L.","family":"Mirshahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-1470","authenticated-orcid":false,"given":"H. Shanker","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0344-9749","authenticated-orcid":false,"given":"Axel","family":"Petzold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9256-6065","authenticated-orcid":false,"given":"Jessica","family":"Tyrrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-184X","authenticated-orcid":false,"given":"Harry D.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Weedon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ganna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8306-6202","authenticated-orcid":false,"given":"Tiinamaija","family":"Tuomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"UKBB Eye & Vision Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"FinnGen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Geisinger-Regeneron DiscovEHR Collaboration","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3581-8980","authenticated-orcid":false,"given":"Richard A.","family":"Oram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3025-4066","authenticated-orcid":false,"given":"Tasanee","family":"Braithwaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"44917_CR1","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1016\/S1474-4422(22)00200-9","volume":"21","author":"A Petzold","year":"2022","unstructured":"Petzold, A. et al. Diagnosis and classification of optic neuritis. Lancet Neurol. 21, 1120\u20131134 (2022).","journal-title":"Lancet Neurol."},{"key":"44917_CR2","doi-asserted-by":"publisher","first-page":"1514","DOI":"10.1001\/jamaneurol.2020.3502","volume":"77","author":"T Braithwaite","year":"2020","unstructured":"Braithwaite, T. et al. Trends in optic neuritis incidence and prevalence in the UK and association with systemic and neurologic disease. JAMA Neurol. 77, 1514\u20131523 (2020).","journal-title":"JAMA Neurol."},{"key":"44917_CR3","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1212\/WNL.45.2.244","volume":"45","author":"M Rodriguez","year":"1995","unstructured":"Rodriguez, M., Siva, A., Cross, S. A., O\u2019Brien, P. C. & Kurland, L. T. Optic neuritis: a population-based study in Olmsted County, Minnesota. Neurology 45, 244\u2013250 (1995).","journal-title":"Neurology"},{"key":"44917_CR4","first-page":"727","volume":"65","author":"Optic Neuritis Study.","year":"2008","unstructured":"Optic Neuritis Study. G. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch. Neurol. 65, 727\u2013732 (2008).","journal-title":"Arch. Neurol."},{"key":"44917_CR5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0002-9394(03)00862-6","volume":"137","author":"RW Beck","year":"2004","unstructured":"Beck, R. W. et al. Visual function more than 10 years after optic neuritis: experience of the optic neuritis treatment trial. Am. J. Ophthalmol. 137, 77\u201383 (2004).","journal-title":"Am. J. Ophthalmol."},{"key":"44917_CR6","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","volume":"17","author":"AJ Thompson","year":"2018","unstructured":"Thompson, A. J. et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17, 162\u2013173 (2018).","journal-title":"Lancet Neurol."},{"key":"44917_CR7","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1001\/archopht.121.7.944","volume":"121","author":"RW Beck","year":"2003","unstructured":"Beck, R. W. et al. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial. Arch. Ophthalmol. 121, 944\u2013949 (2003).","journal-title":"Arch. Ophthalmol."},{"key":"44917_CR8","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1001\/archopht.1997.01100160715008","volume":"115","author":"Optic Neuritis Study Group.","year":"1997","unstructured":"Optic Neuritis Study Group. Visual function 5 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. Arch. Ophthalmol. 115, 1545\u20131552 (1997).","journal-title":"Arch. Ophthalmol."},{"key":"44917_CR9","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/S0021-5155(98)00071-9","volume":"43","author":"M Wakakura","year":"1999","unstructured":"Wakakura, M. et al. Multicenter clinical trial for evaluating methylprednisolone pulse treatment of idiopathic optic neuritis in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG). Jpn J. Ophthalmol. 43, 133\u2013138 (1999).","journal-title":"Jpn J. Ophthalmol."},{"key":"44917_CR10","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0021-5155(98)00072-0","volume":"43","author":"M Wakakura","year":"1999","unstructured":"Wakakura, M. et al. Baseline features of idiopathic optic neuritis as determined by a multicenter treatment trial in Japan. Optic Neuritis Treatment Trial Multicenter Cooperative Research Group (ONMRG). Jpn J. Ophthalmol. 43, 127\u2013132 (1999).","journal-title":"Jpn J. Ophthalmol."},{"key":"44917_CR11","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/jnnp-2019-321653","volume":"91","author":"A Petzold","year":"2020","unstructured":"Petzold, A. et al. Case for a new corticosteroid treatment trial in optic neuritis: review of updated evidence. J. Neurol. Neurosurg. Psychiatry 91, 9\u201314 (2020).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"44917_CR12","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1038\/nrneurol.2014.108","volume":"10","author":"A Petzold","year":"2014","unstructured":"Petzold, A. et al. The investigation of acute optic neuritis: a review and proposed protocol. Nat. Rev. Neurol. 10, 447\u2013458 (2014).","journal-title":"Nat. Rev. Neurol."},{"key":"44917_CR13","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s40123-020-00247-9","volume":"9","author":"T Braithwaite","year":"2020","unstructured":"Braithwaite, T., Wiegerinck, N., Petzold, A. & Denniston, A. Vision loss from atypical optic neuritis: patient and physician perspectives. Ophthalmol. Ther. 9, 215\u2013220 (2020).","journal-title":"Ophthalmol. Ther."},{"key":"44917_CR14","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.brainres.2017.08.012","volume":"1673","author":"E Osinga","year":"2017","unstructured":"Osinga, E., van Oosten, B., de Vries-Knoppert, W. & Petzold, A. Time is vision in recurrent optic neuritis. Brain Res. 1673, 95\u2013101 (2017).","journal-title":"Brain Res."},{"key":"44917_CR15","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2174\/1874325001206010449","volume":"6","author":"KL Chan","year":"2012","unstructured":"Chan, K. L. & Mok, C. C. Glucocorticoid-induced avascular bone necrosis: diagnosis and management. Open Orthop. J. 6, 449\u2013457 (2012).","journal-title":"Open Orthop. J."},{"key":"44917_CR16","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/S1474-4422(22)00289-7","volume":"22","author":"T Kuhlmann","year":"2023","unstructured":"Kuhlmann, T. et al. Multiple sclerosis progression: time for a new mechanism-driven framework. Lancet Neurol. 22, 78\u201388 (2023).","journal-title":"Lancet Neurol."},{"key":"44917_CR17","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1001\/jamaneurol.2023.2815","volume":"80","author":"C Lebrun-Frenay","year":"2023","unstructured":"Lebrun-Frenay, C. et al. Teriflunomide and time to clinical multiple sclerosis in patients with radiologically isolated syndrome: the TERIS randomized clinical trial. JAMA Neurol. 80, 1080\u20131088 (2023).","journal-title":"JAMA Neurol."},{"key":"44917_CR18","unstructured":"International Multiple Sclerosis Genetics Consortium. Electronic address, c.c.y.e. & International Multiple Sclerosis Genetics, C. Low-frequency and rare-coding variation contributes to multiple sclerosis risk. Cell 175, 1679\u20131687.e1677 (2018)."},{"key":"44917_CR19","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1056\/NEJMoa073493","volume":"357","author":"International Multiple Sclerosis Genetics, C.","year":"2007","unstructured":"International Multiple Sclerosis Genetics, C. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med 357, 851\u2013862 (2007).","journal-title":"N. Engl. J. Med"},{"key":"44917_CR20","doi-asserted-by":"publisher","first-page":"eaav7188","DOI":"10.1126\/science.aav7188","volume":"365","author":"International Multiple Sclerosis Genetics, C.","year":"2019","unstructured":"International Multiple Sclerosis Genetics, C. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science 365, eaav7188 (2019).","journal-title":"Science"},{"key":"44917_CR21","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1177\/1352458516630396","volume":"22","author":"A Scalfari","year":"2016","unstructured":"Scalfari, A. et al. The relationship of age with the clinical phenotype in multiple sclerosis. Mult. Scler. 22, 1750\u20131758 (2016).","journal-title":"Mult. Scler."},{"key":"44917_CR22","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1212\/WNL.0000000000003849","volume":"88","author":"MA Gianfrancesco","year":"2017","unstructured":"Gianfrancesco, M. A. et al. Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS. Neurology 88, 1623\u20131629 (2017).","journal-title":"Neurology"},{"key":"44917_CR23","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1212\/NXG.0000000000000097","volume":"2","author":"B Rhead","year":"2016","unstructured":"Rhead, B. et al. Mendelian randomization shows a causal effect of low vitamin D on multiple sclerosis risk. Neurol. Genet. 2, e97 (2016).","journal-title":"Neurol. Genet."},{"key":"44917_CR24","doi-asserted-by":"publisher","first-page":"e662","DOI":"10.1212\/NXI.0000000000000662","volume":"7","author":"BM Jacobs","year":"2020","unstructured":"Jacobs, B. M., Noyce, A. J., Giovannoni, G. & Dobson, R. BMI and low vitamin D are causal factors for multiple sclerosis: a Mendelian Randomization study. Neurol. Neuroimmunol. Neuroinflamm 7, e662 (2020).","journal-title":"Neurol. Neuroimmunol. Neuroinflamm"},{"key":"44917_CR25","first-page":"162","volume":"185","author":"MA Gianfrancesco","year":"2017","unstructured":"Gianfrancesco, M. A. et al. Causal effect of genetic variants associated with body mass index on multiple sclerosis susceptibility. Am. J. Epidemiol. 185, 162\u2013171 (2017).","journal-title":"Am. J. Epidemiol."},{"key":"44917_CR26","doi-asserted-by":"publisher","first-page":"e1002053","DOI":"10.1371\/journal.pmed.1002053","volume":"13","author":"LE Mokry","year":"2016","unstructured":"Mokry, L. E. et al. Obesity and multiple sclerosis: a Mendelian Randomization study. PLoS Med. 13, e1002053 (2016).","journal-title":"PLoS Med."},{"key":"44917_CR27","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1126\/science.abj8222","volume":"375","author":"K Bjornevik","year":"2022","unstructured":"Bjornevik, K. et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375, 296\u2013301 (2022).","journal-title":"Science"},{"key":"44917_CR28","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1007\/s10654-017-0250-2","volume":"32","author":"AK Hedstrom","year":"2017","unstructured":"Hedstrom, A. K. et al. The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement. Eur. J. Epidemiol. 32, 909\u2013919 (2017).","journal-title":"Eur. J. Epidemiol."},{"key":"44917_CR29","doi-asserted-by":"publisher","first-page":"e220902","DOI":"10.1001\/jamanetworkopen.2022.0902","volume":"5","author":"I Kleerekooper","year":"2022","unstructured":"Kleerekooper, I. et al. Associations of alcohol consumption and smoking with disease risk and neurodegeneration in individuals with multiple sclerosis in the United Kingdom. JAMA Netw. Open 5, e220902 (2022).","journal-title":"JAMA Netw. Open"},{"key":"44917_CR30","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/S1474-4422(09)70275-3","volume":"8","author":"PL De Jager","year":"2009","unstructured":"De Jager, P. L. et al. Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol. 8, 1111\u20131119 (2009).","journal-title":"Lancet Neurol."},{"key":"44917_CR31","doi-asserted-by":"publisher","first-page":"fcad041","DOI":"10.1093\/braincomms\/fcad041","volume":"5","author":"JR Breedon","year":"2023","unstructured":"Breedon, J. R. et al. Polygenic risk score prediction of multiple sclerosis in individuals of South Asian ancestry. Brain Commun. 5, fcad041 (2023).","journal-title":"Brain Commun."},{"key":"44917_CR32","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/S0140-6736(12)61179-9","volume":"380","author":"JM Swanson","year":"2012","unstructured":"Swanson, J. M. The UK Biobank and selection bias. Lancet 380, 110 (2012).","journal-title":"Lancet"},{"key":"44917_CR33","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1093\/ije\/dyx206","volume":"47","author":"MR Munafo","year":"2018","unstructured":"Munafo, M. R., Tilling, K., Taylor, A. E., Evans, D. M. & Davey Smith, G. Collider scope: when selection bias can substantially influence observed associations. Int J. Epidemiol. 47, 226\u2013235 (2018).","journal-title":"Int J. Epidemiol."},{"key":"44917_CR34","doi-asserted-by":"publisher","first-page":"e784","DOI":"10.1212\/WNL.0000000000207507","volume":"101","author":"G Bsteh","year":"2023","unstructured":"Bsteh, G. et al. Diagnostic performance of adding the optic nerve region assessed by optical coherence tomography to the diagnostic criteria for multiple sclerosis. Neurology 101, e784\u2013e793 (2023).","journal-title":"Neurology"},{"key":"44917_CR35","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1093\/brain\/awaa361","volume":"144","author":"A Petzold","year":"2021","unstructured":"Petzold, A. et al. Retinal asymmetry in multiple sclerosis. Brain 144, 224\u2013235 (2021).","journal-title":"Brain"},{"key":"44917_CR36","doi-asserted-by":"publisher","first-page":"e0164095","DOI":"10.1371\/journal.pone.0164095","volume":"11","author":"PA Keane","year":"2016","unstructured":"Keane, P. A. et al. Optical coherence tomography in the UK Biobank study\u2014rapid automated analysis of retinal thickness for large population-based studies. PLoS ONE 11, e0164095 (2016).","journal-title":"PLoS ONE"},{"key":"44917_CR37","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1136\/jnnp-2013-305450","volume":"85","author":"IS Mackenzie","year":"2014","unstructured":"Mackenzie, I. S., Morant, S. V., Bloomfield, G. A., MacDonald, T. M. & O\u2019Riordan, J. Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database. J. Neurol. Neurosurg. Psychiatry 85, 76\u201384 (2014).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"44917_CR38","doi-asserted-by":"publisher","first-page":"e697","DOI":"10.1093\/milmed\/usab352","volume":"188","author":"W Gu","year":"2023","unstructured":"Gu, W. et al. Incidence of optic neuritis and the associated risk of multiple sclerosis for service members of U.S. Armed Forces. Mil. Med. 188, e697\u2013e702 (2023).","journal-title":"Mil. Med."},{"key":"44917_CR39","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/imm.13004","volume":"156","author":"MC Ysrraelit","year":"2019","unstructured":"Ysrraelit, M. C. & Correale, J. Impact of sex hormones on immune function and multiple sclerosis development. Immunology 156, 9\u201322 (2019).","journal-title":"Immunology"},{"key":"44917_CR40","doi-asserted-by":"publisher","first-page":"835162","DOI":"10.3389\/fneur.2022.835162","volume":"13","author":"J Leffler","year":"2022","unstructured":"Leffler, J., Trend, S., Gorman, S. & Hart, P. H. Sex-specific environmental impacts on initiation and progression of multiple sclerosis. Front Neurol. 13, 835162 (2022).","journal-title":"Front Neurol."},{"key":"44917_CR41","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1177\/13524585211053155","volume":"28","author":"E Misicka","year":"2022","unstructured":"Misicka, E. et al. A higher burden of multiple sclerosis genetic risk confers an earlier onset. Mult. Scler. 28, 1189\u20131197 (2022).","journal-title":"Mult. Scler."},{"key":"44917_CR42","unstructured":"Our Future Health Research Programme. https:\/\/ourfuturehealth.org.uk\/ (2023)."},{"key":"44917_CR43","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow, C. et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 12, e1001779 (2015).","journal-title":"PLoS Med."},{"key":"44917_CR44","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203\u2013209 (2018).","journal-title":"Nature"},{"key":"44917_CR45","doi-asserted-by":"publisher","first-page":"e1002877","DOI":"10.1371\/journal.pcbi.1002877","volume":"9","author":"A Dilthey","year":"2013","unstructured":"Dilthey, A. et al. Multi-population classical HLA type imputation. PLoS Comput. Biol. 9, e1002877 (2013).","journal-title":"PLoS Comput. Biol."},{"key":"44917_CR46","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1038\/s41416-022-01918-z","volume":"127","author":"HD Green","year":"2022","unstructured":"Green, H. D. et al. Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank. Br. J. Cancer 127, 1534\u20131539 (2022).","journal-title":"Br. J. Cancer"},{"key":"44917_CR47","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1093\/bioinformatics\/btv402","volume":"31","author":"MJ Machiela","year":"2015","unstructured":"Machiela, M. J. & Chanock, S. J. LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics 31, 3555\u20133557 (2015).","journal-title":"Bioinformatics"},{"key":"44917_CR48","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1111\/apt.15826","volume":"52","author":"SA Sharp","year":"2020","unstructured":"Sharp, S. A. et al. A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care. Aliment Pharm. Ther. 52, 1165\u20131173 (2020).","journal-title":"Aliment Pharm. Ther."},{"key":"44917_CR49","doi-asserted-by":"publisher","first-page":"200","DOI":"10.2337\/dc18-1785","volume":"42","author":"SA Sharp","year":"2019","unstructured":"Sharp, S. A. et al. Development and standardization of an improved type 1 diabetes genetic risk score for use in newborn screening and incident diagnosis. Diabetes Care 42, 200\u2013207 (2019).","journal-title":"Diabetes Care"},{"key":"44917_CR50","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1038\/ng.3395","volume":"47","author":"L Moutsianas","year":"2015","unstructured":"Moutsianas, L. et al. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat. Genet. 47, 1107\u20131113 (2015).","journal-title":"Nat. Genet."},{"key":"44917_CR51","doi-asserted-by":"crossref","unstructured":"McKinney, W. A. O. Data structures for statistical computing in Python. In Proceedings of the 9th Python in Science Conference, Vol. 445, 51\u201356 (2010).","DOI":"10.25080\/Majora-92bf1922-00a"},{"key":"44917_CR52","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","volume":"585","author":"CR Harris","year":"2020","unstructured":"Harris, C. R. et al. Array programming with NumPy. Nature 585, 357\u2013362 (2020).","journal-title":"Nature"},{"key":"44917_CR53","doi-asserted-by":"publisher","first-page":"e1007","DOI":"10.1212\/NXI.0000000000001007","volume":"8","author":"BM Jacobs","year":"2021","unstructured":"Jacobs, B. M. et al. Gene-environment interactions in multiple sclerosis: a UK Biobank study. Neurol. Neuroimmunol. Neuroinflamm 8, e1007 (2021).","journal-title":"Neurol. Neuroimmunol. Neuroinflamm"},{"key":"44917_CR54","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1007\/s00415-020-09980-4","volume":"267","author":"M Vandebergh","year":"2020","unstructured":"Vandebergh, M. & Goris, A. Smoking and multiple sclerosis risk: a Mendelian randomization study. J. Neurol. 267, 3083\u20133091 (2020).","journal-title":"J. Neurol."},{"key":"44917_CR55","first-page":"2825","volume":"12","author":"F Pedregosa","year":"2011","unstructured":"Pedregosa, F. et al. Scikit-learn: machine learning in Python. J. Mach. Learn. Res. 12, 2825\u20132830 (2011).","journal-title":"J. Mach. Learn. Res."},{"key":"44917_CR56","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/MCSE.2007.55","volume":"9","author":"JD Hunter","year":"2007","unstructured":"Hunter, J. D. Matplotlib: a 2D graphics environment. Comput. Sci. Eng. 9, 90\u201395 (2007).","journal-title":"Comput. Sci. Eng."},{"key":"44917_CR57","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.21105\/joss.01317","volume":"4","author":"C Davidson-Pilon","year":"2019","unstructured":"Davidson-Pilon, C. Lifelines: survival analysis in Python. J. Open Source Softw. 4, 1317 (2019).","journal-title":"J. Open Source Softw."},{"key":"44917_CR58","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/gim.2015.187","volume":"18","author":"DJ Carey","year":"2016","unstructured":"Carey, D. J. et al. The Geisinger MyCode community health initiative: an electronic health record-linked biobank for precision medicine research. Genet Med. 18, 906\u2013913 (2016).","journal-title":"Genet Med."},{"key":"44917_CR59","doi-asserted-by":"publisher","first-page":"aaf6814","DOI":"10.1126\/science.aaf6814","volume":"354","author":"FE Dewey","year":"2016","unstructured":"Dewey, F. E. et al. Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study. Science 354, aaf6814 (2016).","journal-title":"Science"},{"key":"44917_CR60","unstructured":"FinnGen, I.f.M.M.F.F., University of Helsinki. FinnGen Research Project. Vol. 2023 (2023)."},{"key":"44917_CR61","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","volume":"613","author":"MI Kurki","year":"2023","unstructured":"Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508\u2013518 (2023).","journal-title":"Nature"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-44917-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-44917-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-44917-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T06:03:57Z","timestamp":1709100237000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-44917-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,28]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["44917"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-44917-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2383733\/v1","asserted-by":"object"}]},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,28]]},"assertion":[{"value":"16 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"R.A.O. is a co-investigator on a Randox Laboratories R&D research grant and received translational industry academic funding from Randox Laboratories R&D relating to autoimmune GRS for prediction and classification of disease. There are no established patents, loyalties, or licensing agreements relating to this grant. It is a 3-year grant (February 2022\u20132025). The approximate value is a \u00a32.2 million program grant on GRS across autoimmune disease. A.P. reports personal fees from Novartis, Heidelberg Engineering, Zeiss, grants from Novartis, outside the submitted work; and is part of the steering committee of the OCTiMS study which is sponsored by Novartis and the Angio-OCT steering committee which is sponsored by Zeiss. He does not receive compensation for these activities. Other authors have no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1415"}}