{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:49:54Z","timestamp":1790480994749,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01NS082347"],"award-info":[{"award-number":["R01NS082347"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01NS088155"],"award-info":[{"award-number":["R01NS088155"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["UO1NS045719"],"award-info":[{"award-number":["UO1NS045719"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21NS41986"],"award-info":[{"award-number":["R21NS41986"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NCT00211887"],"award-info":[{"award-number":["NCT00211887"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple sclerosis is a heterogeneous disease with an unpredictable course and a wide range of severity; some individuals rapidly progress to a disabled state whereas others experience only mild symptoms. Though genetic studies have identified variants that are associated with an increased risk of developing multiple sclerosis, no variants have been consistently associated with multiple sclerosis severity. In part, the lack of findings is related to inherent limitations of clinical rating scales; these scales are insensitive to early degenerative changes that underlie disease progression. Optical coherence tomography imaging of the retina and low-contrast letter acuity correlate with and predict clinical and imaging-based outcomes in multiple sclerosis. Therefore, they may serve as sensitive phenotypes to discover genetic predictors of disease course. We conducted a set of genome-wide association studies of longitudinal structural and functional visual pathway phenotypes in multiple sclerosis. First, we assessed genetic predictors of ganglion cell\/inner plexiform layer atrophy in a discovery cohort of 374 patients with multiple sclerosis using mixed-effects models adjusting for age, sex, disease duration, optic neuritis and genetic ancestry and using a combination of single-variant and network-based analyses. For candidate variants identified in discovery, we conducted a similar set of analyses of ganglion cell\/inner plexiform layer thinning in a replication cohort (n = 376). Second, we assessed genetic predictors of sustained loss of 5-letters in low-contrast letter acuity in discovery (n = 582) using multivariable-adjusted Cox proportional hazards models. We then evaluated candidate variants\/pathways in a replication cohort. (n = 253). Results of both studies revealed novel subnetworks highly enriched for connected genes in early complement activation linked to measures of disease severity. Within these networks, C3 was the gene most strongly associated with ganglion cell\/inner plexiform layer atrophy (P = 0.004) and C1QA and CR1 were top results in analysis of sustained low-contrast letter acuity loss. Namely, variant rs158772, linked to C1QA, and rs61822967, linked to CR1, were associated with 71% and 40% increases in risk of sustained LCLA loss, respectively, in meta-analysis pooling discovery and replication cohorts (rs158772: hazard ratio: 1.71; 95% confidence interval 1.30\u20132.25; P = 1.3 \u00d7 10\u22124; rs61822967: hazard ratio: 1.40; 95% confidence interval: 1.16\u20131.68; P = 4.1 \u00d7 10\u22124). In conclusion, early complement pathway gene variants were consistently associated with structural and functional measures of multiple sclerosis severity. These results from unbiased analyses are strongly supported by several prior reports that mechanistically implicated early complement factors in neurodegeneration.<\/jats:p>","DOI":"10.1093\/brain\/awz188","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T19:14:31Z","timestamp":1560194071000},"page":"2722-2736","source":"Crossref","is-referenced-by-count":48,"title":["Early complement genes are associated with visual system degeneration in multiple sclerosis"],"prefix":"10.1093","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-0322","authenticated-orcid":false,"given":"Kathryn C","family":"Fitzgerald","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-9900","authenticated-orcid":false,"given":"Kicheol","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean A","family":"Aston","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Fioravante","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alissa M","family":"Rothman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Krieger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey S","family":"Cofield","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorlan J","family":"Kimbrough","sequence":"additional","affiliation":[{"name":"Department of Neurology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Saidha","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine A","family":"Whartenby","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"},{"name":"Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari J","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M","family":"Mowry","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R","family":"Cutter","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred D","family":"Lublin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio E","family":"Baranzini","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L","family":"De Jager","sequence":"additional","affiliation":[{"name":"Center for Translational and Computational Neuroimmunology, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA"},{"name":"Cell Circuits Program, Broad Institute, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7776-6472","authenticated-orcid":false,"given":"Peter A","family":"Calabresi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA"},{"name":"Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"2019091012305059200_awz188-B1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jns.2012.03.009","article-title":"Low-contrast acuity measures visual improvement in phase 3 trial of natalizumab in relapsing multiple sclerosis","volume":"318","author":"Balcer","year":"2012","journal-title":"J Neurol Sci"},{"key":"2019091012305059200_awz188-B2","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/1352458517690822","article-title":"Validity of low-contrast letter acuity as a visual performance outcome measure for multiple sclerosis","volume":"23","author":"Balcer","year":"2017","journal-title":"Mult Scler"},{"key":"2019091012305059200_awz188-B3","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1007\/s00415-016-8127-y","article-title":"Timing of retinal neuronal and axonal loss in multiple sclerosis: a longitudinal OCT study","volume":"263","author":"Balk","year":"2016","journal-title":"J Neurol"},{"key":"2019091012305059200_awz188-B4","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/hmg\/ddp120","article-title":"Pathway and network-based analysis of genome-wide association studies in multiple sclerosis","volume":"18","author":"Baranzini","year":"2009","journal-title":"Hum Mol Genet"},{"key":"2019091012305059200_awz188-B5","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1093\/brain\/awq192","article-title":"Genetic variation influences glutamate concentrations in brains of patients with multiple sclerosis","volume":"133","author":"Baranzini","year":"2010","journal-title":"Brain"},{"key":"2019091012305059200_awz188-B6","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1016\/j.ophtha.2007.06.047","article-title":"Visual acuity as an outcome measure in clinical trials of retinal diseases","volume":"114","author":"Beck","year":"2007","journal-title":"Ophthalmology"},{"key":"2019091012305059200_awz188-B7","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ng.3656","article-title":"Next-generation genotype imputation service and methods","volume":"48","author":"Das","year":"2016","journal-title":"Nat Genet"},{"key":"2019091012305059200_awz188-B8","doi-asserted-by":"crossref","first-page":"1017.e1","DOI":"10.1016\/j.neurobiolaging.2011.09.033","article-title":"A genome-wide scan for common variants affecting the rate of age-related cognitive decline","volume":"33","author":"De Jager","year":"2012","journal-title":"Neurobiol Aging"},{"key":"2019091012305059200_awz188-B9","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1038\/s41467-018-04332-3","article-title":"A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica","volume":"9","author":"Estrada","year":"2018","journal-title":"Nat Commun"},{"key":"2019091012305059200_awz188-B10","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/brain\/aws363","article-title":"A genome-wide association study of brain lesion distribution in multiple sclerosis","volume":"136","author":"Gourraud","year":"2013","journal-title":"Brain"},{"key":"2019091012305059200_awz188-B11","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1126\/science.aad8373","article-title":"Complement and microglia mediate early synapse loss in Alzheimer mouse models","volume":"352","author":"Hong","year":"2016","journal-title":"Science"},{"key":"2019091012305059200_awz188-B12","doi-asserted-by":"crossref","first-page":"291ra93","DOI":"10.1126\/scitranslmed.aaa9223","article-title":"Genetic variants associated with autoimmunity drive NF\u03baB signaling and responses to inflammatory stimuli","volume":"7","author":"Housley","year":"2015","journal-title":"Sci Transl Med"},{"key":"2019091012305059200_awz188-B13","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.2354","article-title":"Fast and accurate genotype imputation in genome-wide association studies through pre-phasing","volume":"44","author":"Howie","year":"2012","journal-title":"Nat Genet"},{"key":"2019091012305059200_awz188-B14","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature10251","article-title":"Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis","volume":"476","author":"Sawcer","year":"2011","journal-title":"Nature"},{"key":"2019091012305059200_awz188-B15","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1001\/jamaneurol.2016.0980","article-title":"Association of HLA genetic risk burden with disease phenotypes in multiple sclerosis","volume":"73","author":"Isobe","year":"2016","journal-title":"JAMA Neurol"},{"key":"2019091012305059200_awz188-B16","doi-asserted-by":"crossref","first-page":"E302","DOI":"10.1073\/pnas.1716032115","article-title":"Cell-specific and region-specific transcriptomics in the multiple sclerosis model: focus on astrocytes","volume":"115","author":"Itoh","year":"2018","journal-title":"PNAS"},{"key":"2019091012305059200_awz188-B17","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/S1474-4422(09)70275-3","article-title":"Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score","volume":"8","author":"Jager","year":"2009","journal-title":"Lancet Neurol"},{"key":"2019091012305059200_awz188-B18","doi-asserted-by":"crossref","first-page":"e64683","DOI":"10.1371\/journal.pone.0064683","article-title":"Imputing amino acid polymorphisms in human leukocyte antigens","volume":"8","author":"Jia","year":"2013","journal-title":"PLoS One"},{"key":"2019091012305059200_awz188-B19","doi-asserted-by":"crossref","first-page":"D793","DOI":"10.1093\/nar\/gks1055","article-title":"The ConsensusPathDB interaction database: 2013 update","volume":"41","author":"Kamburov","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2019091012305059200_awz188-B20","doi-asserted-by":"crossref","first-page":"e03915","DOI":"10.7554\/eLife.03915","article-title":"Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state","volume":"3","author":"Katz","year":"2014","journal-title":"Elife"},{"key":"2019091012305059200_awz188-B21","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng.2802","article-title":"Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer\u2019s disease","volume":"45","author":"Lambert","year":"2013","journal-title":"Nat Genet"},{"key":"2019091012305059200_awz188-B22","doi-asserted-by":"crossref","first-page":"e1004219","DOI":"10.1371\/journal.pcbi.1004219","article-title":"MAGMA: generalized gene-set analysis of GWAS data","volume":"11","author":"de Leeuw","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"2019091012305059200_awz188-B23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng.3168","article-title":"Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes","volume":"47","author":"Leiserson","year":"2015","journal-title":"Nat. Genet"},{"key":"2019091012305059200_awz188-B24","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"2019091012305059200_awz188-B25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.msard.2012.01.006","article-title":"The CombiRx trial of combined therapy with interferon and glatiramer cetate in relapsing remitting multiple sclerosis: design and baseline characteristics","volume":"1","author":"Lindsey","year":"2012","journal-title":"Mult Scler Relat Disord"},{"key":"2019091012305059200_awz188-B26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ana.23863","article-title":"Randomized study combining interferon & glatiramer acetate in multiple sclerosis","volume":"73","author":"Lublin","year":"2013","journal-title":"Ann Neurol"},{"key":"2019091012305059200_awz188-B27","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.msard.2014.07.003","article-title":"Magnetic resonance imaging correlates of clinical outcomes in early multiple sclerosis","volume":"3","author":"Maghzi","year":"2014","journal-title":"Mult Scler Relat Disord"},{"key":"2019091012305059200_awz188-B28","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S1474-4422(16)00068-5","article-title":"Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study","volume":"15","author":"Martinez-Lapiscina","year":"2016","journal-title":"Lancet Neurol"},{"key":"2019091012305059200_awz188-B29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/gbb.12190","article-title":"Genetic associations with brain cortical thickness in multiple sclerosis","volume":"14","author":"Matsushita","year":"2015","journal-title":"Genes Brain Behav"},{"key":"2019091012305059200_awz188-B30","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ng.3643","article-title":"A reference panel of 64,976 haplotypes for genotype imputation","volume":"48","author":"McCarthy","year":"2016","journal-title":"Nature Genetics"},{"key":"2019091012305059200_awz188-B31","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/glia.23090","article-title":"Complement C3 on microglial clusters in multiple sclerosis occur in chronic but not acute disease: implication for disease pathogenesis","volume":"65","author":"Michailidou","year":"2017","journal-title":"Glia"},{"key":"2019091012305059200_awz188-B32","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/ana.24398","article-title":"Complement C1q-C3-associated synaptic changes in multiple sclerosis hippocampus","volume":"77","author":"Michailidou","year":"2015","journal-title":"Ann Neurol"},{"key":"2019091012305059200_awz188-B33","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.semcdb.2017.06.009","article-title":"Molecular cell biology of complement membrane attack","volume":"72","author":"Morgan","year":"2017","journal-title":"Semin Cell Dev Biol"},{"key":"2019091012305059200_awz188-B34","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/ng.3395","article-title":"Class II HLA interactions modulate genetic risk for multiple sclerosis","volume":"47","author":"Moutsianas","year":"2015","journal-title":"Nature Genetics"},{"key":"2019091012305059200_awz188-B35","doi-asserted-by":"crossref","first-page":"e1006256","DOI":"10.1371\/journal.pgen.1006256","article-title":"The Musashi 1 controls the splicing of photoreceptor-specific exons in the vertebrate retina","volume":"12","author":"Murphy","year":"2016","journal-title":"PLoS Genet"},{"key":"2019091012305059200_awz188-B36","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1534\/genetics.116.188391","article-title":"Gene and network analysis of common variants reveals novel associations in multiple complex diseases","volume":"204","author":"Nakka","year":"2016","journal-title":"Genetics"},{"key":"2019091012305059200_awz188-B37","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3389\/fncel.2014.00380","article-title":"Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis","volume":"8","author":"Orsini","year":"2014","journal-title":"Front Cell Neurosci"},{"key":"2019091012305059200_awz188-B38","first-page":"143933","article-title":"The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility","author":"Patsopoulos","year":"2017","journal-title":"bioRxiv"},{"key":"2019091012305059200_awz188-B39","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1002\/sim.6605","article-title":"A guide to genome-wide association analysis and post-analytic interrogation","volume":"34","author":"Reed","year":"2015","journal-title":"Stat Med"},{"key":"2019091012305059200_awz188-B40","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1186\/1471-2105-9-405","article-title":"iRefIndex: A consolidated protein interaction database with provenance","volume":"9","author":"Razick","year":"2008","journal-title":"BMC Bioinform"},{"key":"2019091012305059200_awz188-B41","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1177\/1352458518760715","article-title":"Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis","volume":"25","author":"Roostaei","year":"2019","journal-title":"Mult Scler"},{"key":"2019091012305059200_awz188-B42","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/ana.24487","article-title":"Optical coherence tomography reflects brain atrophy in multiple sclerosis: a four-year study","volume":"78","author":"Saidha","year":"2015","journal-title":"Ann Neurol"},{"key":"2019091012305059200_awz188-B43","doi-asserted-by":"crossref","first-page":"16002","DOI":"10.1038\/npjschz.2016.2","article-title":"Increased cortical expression of the zinc transporter SLC39A12 suggests a breakdown in zinc cellular homeostasis as part of the pathophysiology of schizophrenia","volume":"2","author":"Scarr","year":"2016","journal-title":"npj Schizophrenia"},{"key":"2019091012305059200_awz188-B44","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0165-5728(97)00241-5","article-title":"The expression of complement regulatory proteins by adult human oligodendrocytes","volume":"84","author":"Scolding","year":"1998","journal-title":"J Neuroimmunol"},{"key":"2019091012305059200_awz188-B45","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","article-title":"The classical complement cascade mediates CNS synapse elimination","volume":"131","author":"Stevens","year":"2007","journal-title":"Cell"},{"key":"2019091012305059200_awz188-B46","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/brain\/awr264","article-title":"Optical coherence tomography segmentation reveals ganglion cell layer pathology after optic neuritis","volume":"135","author":"Syc","year":"2012","journal-title":"Brain"},{"key":"2019091012305059200_awz188-B47","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/ana.22005","article-title":"Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis","volume":"67","author":"Talman","year":"2010","journal-title":"Ann Neurol"},{"key":"2019091012305059200_awz188-B48","article-title":"Astrocyte specific transcriptomics reveal an A1 profile and complement activation in optic nerve during EAE","author":"Tassoni","year":"2018"},{"key":"2019091012305059200_awz188-B49","doi-asserted-by":"crossref","first-page":"e34823","DOI":"10.1371\/journal.pone.0034823","article-title":"The OSCAR-IB consensus criteria for retinal OCT quality assessment","volume":"7","author":"Tewarie","year":"2012","journal-title":"PLoS One"},{"key":"2019091012305059200_awz188-B50","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/ana.20575","article-title":"Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis","volume":"58","author":"Trip","year":"2005","journal-title":"Ann Neurol"},{"key":"2019091012305059200_awz188-B51","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/EDE.0000000000000034","article-title":"Effect decomposition in the presence of an exposure-induced mediator-outcome confounder","volume":"25","author":"Vanderweele","year":"2014","journal-title":"Epidemiology"},{"key":"2019091012305059200_awz188-B52","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3389\/fgene.2014.00370","article-title":"Imputation and quality control steps for combining multiple genome-wide datasets","volume":"5","author":"Verma","year":"2014","journal-title":"Front Genet"},{"key":"2019091012305059200_awz188-B53","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat Commun"},{"key":"2019091012305059200_awz188-B54","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s12974-016-0611-x","article-title":"Complement is activated in progressive multiple sclerosis cortical grey matter lesions","volume":"13","author":"Watkins","year":"2016","journal-title":"J Neuroinflamm"},{"key":"2019091012305059200_awz188-B55","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","article-title":"METAL: fast and efficient meta-analysis of genomewide association scans","volume":"26","author":"Willer","year":"2010","journal-title":"Bioinformatics"},{"key":"2019091012305059200_awz188-B56","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0165-5728(98)00227-6","article-title":"Comparison of C1q-receptors on rat microglia and peritoneal macrophages","volume":"94","author":"Wing","year":"1999","journal-title":"J Neuroimmunol"},{"key":"2019091012305059200_awz188-B57","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1212\/01.wnl.0000278387.15090.5a","article-title":"Relation of vision to global and regional brain MRI in multiple sclerosis","volume":"69","author":"Wu","year":"2007","journal-title":"Neurology"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awz188\/28920628\/awz188.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/142\/9\/2722\/29222403\/awz188.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T13:34:45Z","timestamp":1721396085000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/142\/9\/2722\/5530228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,9]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,7,9]]},"published-print":{"date-parts":[[2019,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awz188","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9]]},"published":{"date-parts":[[2019,7,9]]}}}