The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
Schizophrenia risk from complex variation of complement component 4
Open accessAbstract
Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Moreover, non-Bayesian alternatives—such as models based on disordered neuromodulation (Hu et al. 2015), disrupted synaptic pruning (Sekar et al. 2016), or abnormal cortical dynamics (Uhlhaas et al. 2009)—can also account for similar symptom profiles without invoking probabilistic inference.”
From The myth of the Bayesian brain (2025) · cites this paper as Sekar et al. 2016
Experimental — accuracy not yet measuredIn the citing paper
“To identify core aging-upregulated genes, we looked for overlap in gene expression changes between all brain regions and identified 7 genes (Figure 2D), including markers of reactive as-trocytes, Gfap and Serpina3n (Zamanian et al., 2012), and a component of the complement cascade involved in synapse elimination, C4b (Sekar et al., 2016).”
From The aging astrocyte transcriptome from multiple regions of the mouse brain. (2018) · cites this paper as Sekar et al., 2016
In the citing paper
“Examples include the role of complement in the pathogenesis of acute macular degeneration38, synaptic pruning in schizophrenia64 and autophagy in inflammatory bowel disease65.”
From A brief history of human disease genetics (2020) · cites this paper as [64]
In the citing paper
“Similar functional descriptions have been reported for individual loci implicated in schizo phrenia64, cardiovascular disease104, type 2 diabetes105 and Alzheimer’s disease106, among others.”
From A brief history of human disease genetics (2020) · cites this paper as [64]
In the citing paper
“and indeed many of the genes whose pathological variation confers susceptibility to psychiatric disorders play fundamental roles in brain development 7-9 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [9]
In the citing paper
“However, the neurobiological mechanisms through which genetic variation imparts risk, both individually and in aggregate, are still largely unknown (4–6).”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [5]
In the citing paper
“In SCZ, PRS shows the genome-wide significant association with upregulation of the established risk gene C4A (5).”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [5]
In the citing paper
“Evidence supports hyperactive complement-mediated synaptic pruning in SCZ pathophysiology, presumably through microglia (5)”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [5]
In the citing paper
“the top GWAS-supported, and strongly upregulated, risk gene for SCZ (5).”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [5]
In the citing paper
“and seven variants in the MHC region around the HLA genes, also a region with extensive linkage to known causal variants associated with schizophrenia61.”
From Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia (2016) · cites this paper as [61]
In the citing paper
“Lastly, we recognize that a majority of structural variants (SVs) are not detectable with current genotyping platforms 32.”
From Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects (2017) · cites this paper as [32]
In the citing paper
“Studies of C1q, C4, C3, and CR3 knockout mice suggest that the mechanism of developmental synapse pruning in the retinogeniculate system involves C1q tagging of synapses, opsonization of synapses by C3b, and subsequent phagocytosis of synapses by microglia (Stevens et al., 2007; Schafer et al., 2012; Sekar et al., 2016; Fig. 3 A).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Sekar et al., 2016
In the citing paper
“we found a strong correlation between the risk alleles for SCZ and up-regulation of expression of C4A (complement component 4A; Spearman’s ρ = 0.66, P < 10−16).”
From Gene expression elucidates functional impact of polygenic risk for schizophrenia (2016) · cites this paper as [32]
In the citing paper
“Serious infections increase the risk of subsequently developing schizophrenia [110], and genetic risk factors for schizophrenia increase microglial phagocytosis of synapses [111], leading to the idea that schizophrenia is triggered by excessive microglial phagocytosis of synapses during adolescence [111], and one potential cause of this is increased endotoxin.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [111]
In the citing paper
“Ccl4 antibody specificity was tested using secondary antibody only controls as well as with antibody preadsorption using recombinant Ccl4 protein, as previously described (Sekar et al., 2016).”
From Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain (2018) · cites this paper as Sekar et al., 2016
In the citing paper
“Although not as clear in neurodevelopmental disorder, microglia can have impaired pruning or secrete molecules that contribute to hyperactivity in the CNS [7, 9].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [7]
In the citing paper
“Microglial dysfunction contributes to the pathogenesis of neurodegenerative disorders including Alzheimer’s disease (AD) and neurodevelopmental disorders including autism spectrum disorder and schizophrenia [5-7].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [7]
In the citing paper
“For instance, we found substantial region-dependence in the magnitude and timing of C4b expression (Figure 1E), a complement component and major schizophrenia risk factor (Sekar et al., 2016) that is robustly up-regulated in aged mice (Hahn et al., 2020) and models of neurodegeneration (Zhou et al., 2020).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Sekar et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Bialas, A. R., & Stevens, B. (2013) · Nature Neuroscience · doi:10.1038/nn.3560 · Cited by 519
Self-citationRetractedBiological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
Self-citationThe Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313
Self-citationBrowning, S. R., & Browning, B. L. (2007) · The American Journal of Human Genetics · doi:10.1086/521987 · Cited by 3,217
Synaptic density in human frontal cortex —Developmental changes and effects of aging
Peter R., H. (1979) · Brain Research · doi:10.1016/0006-8993(79)90349-4 · Cited by 2,645
The contribution of de novo coding mutations to autism spectrum disorder
Iossifov, I., O’Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., Stessman, H. A., Witherspoon, K. T., Vives, L., Patterson, K. E., et al. (2014) · Nature · doi:10.1038/nature13908 · Cited by 2,585
Genome-wide association study identifies five new schizophrenia loci
The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011) · Nature Genetics · doi:10.1038/ng.940 · Cited by 1,919
Common variants conferring risk of schizophrenia
†Genetic Risk and Outcome in Psychosis (GROUP), Stefansson, H., Ophoff, R. A., Steinberg, S., Andreassen, O. A., Cichon, S., Rujescu, D., Werge, T., Pietiläinen, O. P. H., Mors, O., et al. (2009) · Nature · doi:10.1038/nature08186 · Cited by 1,677
Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia
Glantz, L. A., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.65 · Cited by 1,636
De novo mutations in schizophrenia implicate synaptic networks
Fromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D. M., et al. (2014) · Nature · doi:10.1038/nature12929 · Cited by 1,617
Self-citationExtraordinary neoteny of synaptic spines in the human prefrontal cortex
Petanjek, Z., Judaš, M., Šimić, G., Rašin, M. R., Uylings, H. B. M., Rakic, P., & Kostović, I. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105108108 · Cited by 1,411
Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence?
Feinberg, I. (1982) · Journal of Psychiatric Research · doi:10.1016/0022-3956(82)90038-3 · Cited by 1,395
A polygenic burden of rare disruptive mutations in schizophrenia
Purcell, S. M., Moran, J. L., Fromer, M., Ruderfer, D., Solovieff, N., Roussos, P., O’Dushlaine, C., Chambert, K., Bergen, S. E., Kähler, A., et al. (2014) · Nature · doi:10.1038/nature12975 · Cited by 1,385
Self-citationCommon variants on chromosome 6p22.1 are associated with schizophrenia
Shi, J., Levinson, D. F., Duan, J., Sanders, A. R., Zheng, Y., Pe’er, I., Dudbridge, F., Holmans, P., Whittemore, A. S., Mowry, B. J., et al. (2009) · Nature · doi:10.1038/nature08192 · Cited by 1,154
Raychaudhuri, S., Sandor, C., Stahl, E. A., Freudenberg, J., Lee, H. S., Jia, X., Alfredsson, L. S., Padyukov, L., Klareskog, L., Worthington, J., et al. (2012) · Nature Genetics · doi:10.1038/ng.1076 · Cited by 967
Kirov, G., Pocklington, A. J., Holmans, P., Ivanov, D., Ikeda, M., Ruderfer, D., Moran, J., Chambert, K., Toncheva, D., Georgieva, L., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.154 · Cited by 844
The evolution of distributed association networks in the human brain
Buckner, R. L., & Krienen, F. M. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.09.017 · Cited by 836 · cited 1×
“In humans, adolescence and early adulthood bring extensive elimination of synapses in distributed association regions of cerebral cortex, such as the prefrontal cortex, that have greatly expanded in recent human evolution 37–40 .”
BackgroundReduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia
Garey, L. J., Ong, W., Patel, T. S., Kanani, M., Davis, A., Mortimer, A. M., Barnes, T., & Hirsch, S. R. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.65.4.446 · Cited by 719
Self-citationImputing Amino Acid Polymorphisms in Human Leukocyte Antigens
Jia, X., Han, B., Önengüt-Gümüşcü, S., Chen, W., CONCANNON, P. J., Rich, S. S., Raychaudhuri, S., & de Bakker, P. I. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064683 · Cited by 650
Cannon, T. D., Chung, Y., He, G., Sun, D., Jacobson, A., van Erp, T. G. M., McEwen, S., Addington, J., Bearden, C. E., Cadenhead, K., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.023 · Cited by 599
Dendritic spine pathology in schizophrenia
Glausier, J. R., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.044 · Cited by 581
Developmental Remodeling of the Retinogeniculate Synapse
Chen, C., & Regehr, W. G. (2000) · Neuron · doi:10.1016/s0896-6273(00)00166-5 · Cited by 439
Carroll, M. C., Campbell, R. D., Bentley, D., & Porter, R. R. (1984) · Nature · doi:10.1038/307237a0 · Cited by 432
Self-citationLarge multiallelic copy number variations in humans
Handsaker, R. E., Doren, V. V., Berman, J. R., Genovese, G., Kashin, S., Boettger, L. M., & McCarroll, S. A. (2015) · Nature Genetics · doi:10.1038/ng.3200 · Cited by 388
Self-citationRegulation of the B cell response to T-dependent antigens by classical pathway complement
Fischer, M. B., Ma, M., Goerg, S., et al. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.2.549 · Cited by 364
Variation analysis and gene annotation of eight MHC haplotypes: The MHC Haplotype Project
Horton, R., Gibson, R., Coggill, P. C., Miretti, M. M., Allcock, R. J. N., Almeida, J. P., Forbes, S. A., Gilbert, J. G. R., Halls, K., Harrow, J., et al. (2008) · Immunogenetics · doi:10.1007/s00251-007-0262-2 · Cited by 321
Cannon, T. D., Thompson, P. M., van Erp, T. G. M., Toga, A. W., Poutanen, V.-P., HUTTUNEN, M. O., Lönnqvist, J. K., Standerskjold-Nordenstam, C.-G., Narr, K. L., Khaledy, M., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052023499 · Cited by 315
A comparison of the properties of two classes, C4A and C4B, of the human complement component C4
Law, S. K., Dodds, A. W., & Porter, R. R. (1984) · The EMBO Journal · doi:10.1002/j.1460-2075.1984.tb02052.x · Cited by 303
Isenman, D. E., & Young, J. R. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.132.6.3019 · Cited by 241
Synapse elimination and learning rules co-regulated by MHC class I H2-Db
Lee, H., Brott, B. K., Kirkby, L. A., Adelson, J. D., Cheng, S., Feller, M. B., Datwani, A., & Shatz, C. J. (2014) · Nature · doi:10.1038/nature13154 · Cited by 228
Sretavan, D. W., & Shatz, C. J. (1986) · Journal of Neuroscience · doi:10.1523/jneurosci.06-01-00234.1986 · Cited by 227
The reaction mechanism of the internal thioester in the human complement component C4
Dodds, A. W., Ren, X. D., Willis, A. C., & Law, S. K. A. (1996) · Nature · doi:10.1038/379177a0 · Cited by 224
Classical MHCI Molecules Regulate Retinogeniculate Refinement and Limit Ocular Dominance Plasticity
Datwani, A., McConnell, M. J., Kanold, P. O., Micheva, K. D., Busse, B., Shamloo, M., Smith, S. J., & Shatz, C. J. (2009) · Neuron · doi:10.1016/j.neuron.2009.10.015 · Cited by 212
Prenatal development of functional connections in the cat's retinogeniculate pathway
Shatz, C. J., & Kirkwood, P. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-05-01378.1984 · Cited by 174
Modeling psychiatric disorders for developing effective treatments
Kaiser, T., & Feng, G. (2015) · Nature Medicine · doi:10.1038/nm.3935 · Cited by 157
Dangel, A. W., Mendoza, A. R., Menachery, C. D., Baker, B., Daniel, C., Carroll, M., Wu, L., & Yu, C. Y. (1994) · Immunogenetics · doi:10.1007/bf00177825 · Cited by 148
Self-citationHowson, J. M. M., Walker, N. M., Clayton, D. G., & Todd, J. A. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.01001.x · Cited by 135
Yang, Y., Chung, E. K., Zhou, B., et al. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.5.2734 · Cited by 121
Escudero‐Esparza, A., Kalchishkova, N., Kurbasic, E., Jiang, W. G., & Blom, A. M. (2013) · The FASEB Journal · doi:10.1096/fj.13-230706 · Cited by 103
Structure and organization of the C4 genes
Carroll, M. C., Belt, T., Pálsdóttir, Á., & Porter, R. R. (1984) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1984.0098 · Cited by 91
Self-citationSuntsova, M., Gogvadze, E. V., Salozhin, S. V., Гайфуллин, Н., Eroshkin, F. M., Dmitriev, S. E., Martynova, N. Y., Kulikov, K., Malakhova, G., Тухбатова, Г. Р., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318172110 · Cited by 85
Unbiased analysis of bulk axonal segregation patterns
Torborg, C. L., & Feller, M. B. (2004) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2003.11.019 · Cited by 85
Classical pathway complement activity in schizophrenia
Hakobyan, S., Boyajyan, A. S., & Sim, R. B. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.10.024 · Cited by 79
Increased complement classical and mannan-binding lectin pathway activities in schizophrenia
Mayilyan, K. R., Arnold, J. N., Presanis, J. S., Soghoyan, A. F., & Sim, R. B. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.06.051 · Cited by 72
X-ray Crystal Structure of the C4d Fragment of Human Complement Component C4
van den Elsen, J. M. H., Martín, A., Wong, V., Clemenza, L., Rose, D. R., & Isenman, D. E. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00854-9 · Cited by 65
Complement C4B protein in schizophrenia
Mayilyan, K. R., Dodds, A. W., Boyajyan, A. S., Soghoyan, A. F., & Sim, R. B. (2008) · The World Journal of Biological Psychiatry · doi:10.1080/15622970701227803 · Cited by 44
Complement Factor C4 in Schizophrenia
Rudduck, C., Beckman, L. E., n, G. F. E., et al. (1985) · Human Heredity · doi:10.1159/000153549 · Cited by 30
Assessment of complement C4 gene copy number using the paralog ratio test
Fernando, M. M. A., Boteva, L., Morris, D. L., Zhou, B., Wu, Y. L., Lokki, M., Yu, C. Y., Rioux, J. D., Hollox, E. J., & Vyse, T. J. (2010) · Human Mutation · doi:10.1002/humu.21259 · Cited by 29
Human endogenous retroviruses with transcriptional potential in the brain
Nakamura, A., Okazaki, Y., Sugimoto, J., Oda, T., & Jinno, Y. (2003) · Journal of Human Genetics · doi:10.1007/s10038-003-0081-8 · Cited by 29
Nonaka, M., Nakayama, K., Yeul, Y. D., et al. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.8.2989 · Cited by 27
Investigation of Complement C4B Deficiency in Schizophrenia
Schroers, R., Nöthen, M. M., Rietschel, M., Albus, M., Maier, W., Schwab, S., Wildenauer, D., Fimmers, R., Propping, P., & Dewald, G. (1997) · Human Heredity · doi:10.1159/000154424 · Cited by 23
Bánlaki, Z., Doleschall, M., Rajczy, K., Füst, G., & Szilágyi, Á. (2012) · Genes and Immunity · doi:10.1038/gene.2012.29 · Cited by 21
Illarionova, A. E., Vinogradova, T. V., & Sverdlov, E. D. (2006) · Virology · doi:10.1016/j.virol.2006.06.027 · Cited by 19
Huttenlocher (1997) · doi:10.1002/(sici)1096-9861(19971020)387:2
Flagged first, then by citations
Cited by
Sorted by citations
10 Years of GWAS Discovery: Biology, Function, and Translation
Visscher, P. M., Wray, N. R., Zhang, Q., Sklar, P., McCarthy, M. I., Brown, M. A., & Yang, J. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.06.005 · Cited by 3,719
An Expanded View of Complex Traits: From Polygenic to Omnigenic
Boyle, E. A., Li, Y. I., & Pritchard, J. K. (2017) · Cell · doi:10.1016/j.cell.2017.05.038 · Cited by 2,851
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., Bryois, J., Chen, C.-Y., Dennison, C. A., Hall, L. S., et al. (2022) · Nature · doi:10.1038/s41586-022-04434-5 · Cited by 2,964
Self-citationReactive Astrocytes: Production, Function, and Therapeutic Potential
Liddelow, S. A., & Barres, B. A. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.006 · Cited by 2,336
Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., Segel, M., Nemesh, J., Saunders, A., et al. (2018) · doi:10.1101/406140 · Cited by 2,225
Self-citation
Metadata
- Authors
- Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., Genovese, G., Rose, S. A., Handsaker, R. E., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly, M. J., Carroll, M. C., Stevens, B., & McCarroll, S. A.
- Affiliations
- Broad Institute (US)
- Boston Children's Hospital (US)
- Corresponding author
- McCarroll, Steven A.
- ORCID
- Venue
- Nature
- Published
- 2016-01-27
- Volume
- 530
- Issue
- 7589
- Pages
- 177-183
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4752392
- OpenAlex
- W2255138985
- Cited by
- 2,394
- References
- 56
- Citations by year
- 2026: 177 · 2025: 185 · 2024: 202 · 2023: 212 · 2022: 215 · 2021: 261 · 2020: 251 · 2019: 236 · 2018: 241 · 2017: 233 · 2016: 171
- FWCI
- 224.40
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-12-15)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (acceptedVersion)
- Lancaster EPrints (Lancaster University) (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Lirias (submittedVersion)
- GRO (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- UCrea (University of Cantabria) (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- National Institute for Health and Care Research (PDA/02/06/016)
- Lundbeckfonden (R155-2014-1724)
- Medical Research Council (MR/P005748/1, MR/L010305/1)
- National Institute of Mental Health (R01MH042191, R01MH077139, U01MH105641, R01MH085548)
- National Human Genome Research Institute (R01HG006855, T32HG002295)
- National Institute of General Medical Sciences (T32GM007753)
- National Institute of Allergy and Infectious Diseases (T32AI074549)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD090255)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- schizophrenia, complement C4, C4A, C4b, major histocompatibility complex, genetic association, synaptic pruning, classical complement pathway, brain gene expression, mouse model
- MeSH terms
- Alleles, Amino Acid Sequence, Animals, Axons, Base Sequence, Brain, Complement Pathway, Classical, Complement C4, Dendrites, Gene Expression Regulation, Haplotypes, Humans, Major Histocompatibility Complex, Neuronal Plasticity, Risk Factors, RNA, Messenger, Schizophrenia, Synapses, Genetic Variation, Gene Dosage, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Models, Animal, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
