Truncating variant burden in high-functioning autism and pleiotropic effects of LRP1 across psychiatric phenotypes
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Abstract
Background: Previous research has implicated de novo and inherited truncating mutations in autism-spectrum disorder. We aim to investigate whether the load of inherited truncating mutations contributes similarly to high-functioning autism, and to characterize genes that harbour de novo variants in high-functioning autism. Methods: We performed whole-exome sequencing in 20 high-functioning autism families (average IQ = 100). Results: We observed no difference in the number of transmitted versus nontransmitted truncating alleles for high-functioning autism (117 v. 130, p = 0.78). Transmitted truncating and de novo variants in high-functioning autism were not enriched in gene ontology (GO) or Kyoto Encyclopedia of Genes and Genomes (KEGG) categories, or in autism-related gene sets. However, in a patient with high-functioning autism we identified a de novo variant in a canonical splice site of LRP1, a postsynaptic density gene that is a target for fragile X mental retardation protein (FRMP). This de novo variant leads to in-frame skipping of exon 29, removing 2 of 6 blades of the β-propeller domain 4 of LRP1, with putative functional consequences. Large data sets implicate LRP1 across a number of psychiatric disorders: de novo variants are associated with autism-spectrum disorder ( p = 0.039) and schizophrenia ( p = 0.008) from combined sequencing projects; common variants using genome-wide association study data sets from the Psychiatric Genomics Consortium show gene-based association in schizophrenia ( p = 6.6 × E −07 ) and in a meta-analysis across 7 psychiatric disorders ( p = 2.3 × E −03 ); and the burden of ultra-rare pathogenic variants has been shown to be higher in autism-spectrum disorder ( p = 1.2 × E −05 ), using whole-exome sequencing from 6135 patients with schizophrenia, 1778 patients with autism-spectrum disorder and 7875 controls. Limitations: We had a limited sample of patients with high-functioning autism, related to difficulty in recruiting probands with high cognitive performance and no family history of psychiatric disorders. Conclusion: Previous studies and ours suggest an effect of truncating mutations restricted to severe autism-spectrum disorder phenotypes that are associated with intellectual disability. We provide evidence for pleiotropic effects of common and rare variants in the LRP1 gene across psychiatric phenotypes.
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Other lipoprotein receptors from the same family, such as LRP2 and LRP8, have been implicated in autism and psychosis.
“Similarly, other lipoprotein receptors from the same family, such as LRP2 and LRP8, have been implicated in autism and psychosis [60,61].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [60]
A de novo variant in a canonical splice site of LRP1 has recently been identified in ASD patients.
“Interestingly, a de novo variant in a canonical splice site of LRP1 has recently been identified in ASD patients [60].”
From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [60]
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PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587 · see citing works
Biological 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 · see citing works
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling
Arnold, K., Bordoli, L., Kopp, J., & Schwede, T. F. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti770 · Cited by 6,951 · see citing works
SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information
Biasini, M., Bienert, S., Waterhouse, A. M., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Cassarino, T. G., Bertoni, M., Bordoli, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku340 · Cited by 4,621 · see citing works
MAGMA: Generalized Gene-Set Analysis of GWAS Data
de Leeuw, C. A., Mooij, J. M., Heskes, T., & Posthuma, D. (2015) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1004219 · Cited by 3,653 · see citing works
eQTLGen, Wray, N. R., 23andMe, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., Adams, M. J., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0090-3 · Cited by 3,005 · see citing works
Synaptic, transcriptional and chromatin genes disrupted in autism
Study, T. D., De Rubeis, S., Autism, H. M. C. F., UK10K Consortium, The Autism Sequencing Consortium, He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., et al. (2014) · Nature · doi:10.1038/nature13772 · Cited by 2,746 · see citing works
Global Prevalence of Autism and Other Pervasive Developmental Disorders
Elsabbagh, M., Divan, G., Koh, Y., Kim, Y. S., Kauchali, S., Marcín, C., Montiel‐Nava, C., Patel, V., Paula, C. S., Wang, C., et al. (2012) · Autism Research · doi:10.1002/aur.239 · Cited by 2,636 · see citing works
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 · see citing works
Human Splicing Finder: an online bioinformatics tool to predict splicing signals
Desmet, F.-O., Hamroun, D., Lalande, M., Collod‐Béroud, G., Claustres, M., & Béroud, C. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp215 · Cited by 2,500 · see citing works
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) · Nature Genetics · doi:10.1038/ng.2711 · Cited by 2,263 · see citing works
Self-citationADHD Working Group of the Psychiatric Genomics Consortium (PGC), Demontis, D., Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Baldursson, G., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0269-7 · Cited by 2,203 · see citing works
Self-citationSporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · see citing works
Spatio-temporal transcriptome of the human brain
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., Sousa, A. M. M., Pletikos, M., Meyer, K. A., Sedmak, G., et al. (2011) · Nature · doi:10.1038/nature10523 · Cited by 2,084 · see citing works
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Maximum Entropy Modeling of Short Sequence Motifs with Applications to RNA Splicing Signals
Yeo, G. W.-M., & Burge, C. B. (2004) · Journal of Computational Biology · doi:10.1089/1066527041410418 · Cited by 2,042 · see citing works
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., et al. (2012) · Nature · doi:10.1038/nature11011 · Cited by 1,734 · see citing works
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 · see citing works
Genome-wide association study identifies 30 loci associated with bipolar disorder
eQTLGen Consortium, Stahl, E. A., BIOS Consortium, the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., Mattheisen, M., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0397-8 · Cited by 1,519 · see citing works
Insights into autism spectrum disorder genomic architecture and biology from 71 risk loci
Sanders, S. J., He, X., Willsey, A. J., Ercan-Sencicek, A. G., Samocha, K. E., Cicek, A. E., Murtha, M. T., Bal, V. H., Bishop, S. L., Dong, S., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.016 · Cited by 1,430 · see citing works
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 · see citing works
Most genetic risk for autism resides with common variation
Gaugler, T., Klei, L., Sanders, S. J., Bodea, C. A., Goldberg, A. P., Lee, A. B., Mahajan, M., Manaa, D., Pawitan, Y., Reichert, J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3039 · Cited by 1,239 · see citing works
The human splicing code reveals new insights into the genetic determinants of disease
Xiong, H. Y., Alipanahi, B., Lee, L. J., Bretschneider, H., Merico, D., Yuen, R. K. C., Hua, Y., Gueroussov, S., Najafabadi, H. S., Hughes, T., et al. (2014) · Science · doi:10.1126/science.1254806 · Cited by 1,225 · see citing works
A mega-analysis of genome-wide association studies for major depressive disorder
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Ripke, S., Wray, N. R., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., Byrne, E. M., Blackwood, D. H. R., Boomsma, D. I., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.21 · Cited by 1,120 · see citing works
High-Resolution Comparative Modeling with RosettaCM
Song, Y., DiMaio, F., Wang, R. Y., Kim, D. E., Miles, C., Brunette, T., Thompson, J., & Baker, D. A. (2013) · Structure · doi:10.1016/j.str.2013.08.005 · Cited by 1,079 · see citing works
Common genetic variants on 5p14.1 associate with autism spectrum disorders
Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J. T., Abrahams, B. S., Salyakina, D., Imielinski, M., Bradfield, J. P., Sleiman, P. M. A., et al. (2009) · Nature · doi:10.1038/nature07999 · Cited by 989 · see citing works
Betancur, C. (2011) · Brain Research · doi:10.1016/j.brainres.2010.11.078 · Cited by 954 · see citing works
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
C Yuen, R. K., Merico, D., Bookman, M., L Howe, J., Thiruvahindrapuram, B., Patel, R. V., Whitney, J., Deflaux, N., Bingham, J., Wang, Z., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4524 · Cited by 844 · see citing works
The Heritability of Autism Spectrum Disorder
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Hultman, C., Larsson, H., & Reichenberg, A. (2017) · JAMA · doi:10.1001/jama.2017.12141 · Cited by 776 · see citing works
Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways
The Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium (2015) · Nature Neuroscience · doi:10.1038/nn.3922 · Cited by 755 · see citing works
Temporal dynamics and genetic control of transcription in the human prefrontal cortex
Colantuoni, C., Lipska, B. K., Ye, T., Hyde, T. M., Tao, R., Leek, J. T., Colantuoni, E. A., Elkahloun, A. G., Herman, M. M., Weinberger, D. R., et al. (2011) · Nature · doi:10.1038/nature10524 · Cited by 685 · see citing works
The genetics of autistic disorders and its clinical relevance: a review of the literature
Freitag, C. M. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001896 · Cited by 638 · see citing works
A genome-wide linkage and association scan reveals novel loci for autism
The Gene Discovery Project of Johns Hopkins & the Autism Consortium, Weiss, L. A., & Arking, D. E. (2009) · Nature · doi:10.1038/nature08490 · Cited by 619 · see citing works
Revealing the complex genetic architecture of obsessive–compulsive disorder using meta-analysis
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS) (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.154 · Cited by 618 · see citing works
A genome-wide scan for common alleles affecting risk for autism
Anney, R., Klei, L., Pinto, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., Sykes, N., Pagnamenta, A. T., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq307 · Cited by 593 · see citing works
The Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) · Molecular Autism · doi:10.1186/s13229-017-0137-9 · Cited by 587 · see citing works
Excess of rare, inherited truncating mutations in autism
Krumm, N., Turner, T. N., Baker, C., Vives, L., Mohajeri, K., Witherspoon, K., Raja, A., Coe, B. P., Stessman, H. A., He, Z.-X., et al. (2015) · Nature Genetics · doi:10.1038/ng.3303 · Cited by 587 · see citing works
Duncan, L. E., Yılmaz, Z., Gaspar, H., Walters, R. K., Goldstein, J., Anttila, V., Bulik-Sullivan, B. K., Ripke, S., Thornton, L., Hinney, A., et al. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.16121402 · Cited by 549 · see citing works
Whole-genome sequencing of quartet families with autism spectrum disorder
Yuen, R. K. C., Thiruvahindrapuram, B., Merico, D., Walker, S., Tammimies, K., Hoang, N., Chrysler, C., Nalpathamkalam, T., Pellecchia, G., Liu, Y., et al. (2015) · Nature Medicine · doi:10.1038/nm.3792 · Cited by 514 · see citing works
Structure prediction for CASP8 with all‐atom refinement using Rosetta
Raman, S., Vernon, R. M., Thompson, J., Tyka, M. D., Sadreyev, R. I., Pei, J., Kim, D. E., Kellogg, E. H., DiMaio, F., Lange, O. F., et al. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22540 · Cited by 511 · see citing works
Characterization of the proteome, diseases and evolution of the human postsynaptic density
Bayés, À., van de Lagemaat, L. N., Collins, M. O., Croning, M. D. R., Whittle, I. R., Choudhary, J. S., & Grant, S. G. N. (2011) · Nature Neuroscience · doi:10.1038/nn.2719 · Cited by 499 · see citing works
The role of de novo mutations in the genetics of autism spectrum disorders
Ronemus, M., Iossifov, I., Levy, D., & Wigler, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3585 · Cited by 390 · see citing works
Zhan, X., Hu, Y., Li, B., Abecasis, G. R., & Liu, D. J. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw079 · Cited by 374 · see citing works
Kosmicki, J. A., Samocha, K. E., Howrigan, D. P., Sanders, S. J., Slowikowski, K., Lek, M., Karczewski, K. J., Cutler, D. J., Devlin, B., Roeder, K., et al. (2017) · Nature Genetics · doi:10.1038/ng.3789 · Cited by 340 · see citing works
Idring, S., Lundberg, M., Sturm, H., Dalman, C., Gumpert, C., Rai, D., Lee, B. K., & Magnusson, C. (2015) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2336-y · Cited by 296 · see citing works
Liu, Q., Trotter, J., Zhang, J., Peters, M. M., Cheng, H., Bao, J., Han, X., Weeber, E. J., & Bu, G. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4067-10.2010 · Cited by 268 · see citing works
The neuroanatomy of autism – a developmental perspective
Donovan, A. P. A., & Basson, M. A. (2016) · Journal of Anatomy · doi:10.1111/joa.12542 · Cited by 266 · see citing works
The Genotype-Tissue Expression (GTEx) project
Lonsdale, J., Thomas, J., Salvatore, M., Phillips, R., Lo, E., Shad, S., Hasz, R., Walters, G., Garcia, F., Young, N., et al. (2013) · Nature Genetics · doi:10.1038/ng.2653 · Cited by 263 · see citing works
Zlokovic, B. V., Deane, R., Sagare, A. P., Bell, R. D., & Winkler, E. A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07002.x · Cited by 261 · see citing works
The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder
Masi, A., Glozier, N., Dale, R. C., & Guastella, A. J. (2017) · Neuroscience Bulletin · doi:10.1007/s12264-017-0103-8 · Cited by 260 · see citing works
Jeon, H., Meng, W., Takagi, J., Eck, M. J., Springer, T. A., & Blacklow, S. C. (2001) · Nature Structural Biology · doi:10.1038/88556 · Cited by 225 · see citing works
denovo-db: a compendium of humande novovariants
Turner, T. N., Qian, Y., Krumm, N., Huddleston, J., Hoekzema, K., Stessman, H. A. F., Doebley, A.-L., Bernier, R., Nickerson, D. A., & Eichler, E. E. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw865 · Cited by 213 · see citing works
Li, J., Cai, T., Jiang, Y. W., Chen, H., He, X., Chen, C., Li, X., Shao, Q., Xia, R., Li, Z., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.40 · Cited by 208 · see citing works
Crystal structures of the extracellular domain of LRP6 and its complex with DKK1
Cheng, Z., Biechele, T. L., Wei, Z., Morrone, S. R., Moon, R. T., Wang, L., & Xu, W. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2139 · Cited by 203 · see citing works
Copy Number Variations and Cognitive Phenotypes in Unselected Populations
Männik, K., Mägi, R., Macé, A., Cole, B., Guyatt, A. L., Shihab, H. A., Maillard, A. M., Alavere, H., Kolk, A., Reigo, A., et al. (2015) · JAMA · doi:10.1001/jama.2015.4845 · Cited by 201 · see citing works
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains
Geisheker, M. R., Heymann, G., Wang, T., Coe, B. P., Turner, T. N., Stessman, H. A. F., Hoekzema, K., Kvarnung, M., Shaw, M. A., Friend, K. L., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4589 · Cited by 175 · see citing works
LRP1 modulates the microglial immune response via regulation of JNK and NF-κB signaling pathways
Yang, L., Liu, C., Zheng, H., Kanekiyo, T., Atagi, Y., Jia, L., Wang, D., N’Songo, A., Can, D., Xu, H., et al. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0772-7 · Cited by 154 · see citing works
Brain region-specific altered expression and association of mitochondria-related genes in autism
Anitha, A., Nakamura, K., Thanseem, I., Yamada, K., Iwayama, Y., Toyota, T., Matsuzaki, H., Miyachi, T., Yamada, S., Tsujii, M., et al. (2012) · Molecular Autism · doi:10.1186/2040-2392-3-12 · Cited by 148 · see citing works
Mantuano, E., Brifault, C., Lam, M. S., Azmoon, P., Gilder, A. S., & Gonias, S. L. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515480113 · Cited by 141 · see citing works
Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain
Liu, C., Hu, J., Tsai, C., Yue, M., Melrose, H. L., Kanekiyo, T., & Bu, G. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.5180-14.2015 · Cited by 140 · see citing works
Toma, C., Torrico, B., Hervás, A., Valdés-Mas, R., Tristán-Noguero, A., Padillo, V, Maristany, M., Salgado, M., Arenas, C., Puente, X. S., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.106 · Cited by 114 · see citing works
Self-citationYamanaka, Y., Faghihi, M. A., Magistri, M., Álvarez-García, Ó., Lotz, M., & Wahlestedt, C. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.011 · Cited by 99 · see citing works
Intellectual development in autism spectrum disorders: new insights from longitudinal studies
Vivanti, G., Barbaro, J., Hudry, K., Dissanayake, C., & Prior, M. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00354 · Cited by 90 · see citing works
Ganna, A., Genovese, G., Howrigan, D. P., Byrnes, A., Kurki, M., Zekavat, S. M., Whelan, C. W., Kals, M., Nivard, M. G., Bloemendal, A., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4404 · Cited by 89 · see citing works
Psychiatric disorders and mitochondrial dysfunctions.
Marazziti, D., Baroni, S., Picchetti, M., Landi, P., Silvestri, S., Vatteroni, E., & Dell’Osso, M. C. (2012) · PubMed · Cited by 83 · see citing works
From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition
Young, A. M. H., Chakrabarti, B., Roberts, D., Lai, M.-C., Suckling, J., & Baron-Cohen, S. (2016) · Molecular Autism · doi:10.1186/s13229-016-0068-x · Cited by 76 · see citing works
LRP1 expression in microglia is protective during CNS autoimmunity
Chuang, T.-Y., Guo, Y. X., Seki, S. M., Rosen, A. M., Johanson, D. M., Mandell, J. W., Lucchinetti, C. F., & Gaultier, A. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0343-2 · Cited by 74 · see citing works
Auderset, L., Cullen, C. L., & Young, K. M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155878 · Cited by 62 · see citing works
van de Vondervoort, I., Poelmans, G., Aschrafi, A., Pauls, D., Buitelaar, J., Glennon, J., & Franke, B. (2016) · Journal of Psychiatry & Neuroscience · doi:10.1503/jpn.140327 · Cited by 61 · see citing works
Ionita-Laza, I., Makarov, V., & Buxbaum, J. D. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.04.010 · Cited by 57 · see citing works
Lack of replication of previous autism spectrum disorder GWAS hits in European populations
Torrico, B., Chiocchetti, A. G., Bacchelli, E., Trabetti, E., Hervás, A., Franke, B., Buitelaar, J. K., Rommelse, N., Yousaf, A., Duketis, E., et al. (2017) · Autism Research · doi:10.1002/aur.1662 · Cited by 47 · see citing works
Self-citationLi, J., Cai, T., Jiang, Y., Chen, H., He, X., Chen, C., Li, X., Shao, Q., Ran, X., Li, Z., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.58 · Cited by 47 · see citing works
Torrico, B., Fernàndez‐Castillo, N., Amaia Hervas, G., Milà, M., Salgado, M., Rueda, I., Buitelaar, J. K., Rommelse, N. N. J., Oerlemans, A. M., Bralten, J., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2015.37 · Cited by 42 · see citing works
Self-citationAn examination of multiple classes of rare variants in extended families with bipolar disorder
Claudio Toma, A., Shaw, A. D., Allcock, R. J. N., Heath, A., Pierce, K. D., Mitchell, P. B., Schofield, P. R., & Fullerton, J. M. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0113-y · Cited by 42 · see citing works
Self-citationCommon and rare variants of microRNA genes in autism spectrum disorders
Claudio Toma, A., Torrico, B., Amaia Hervas, G., Salgado, M., Rueda, I., Valdés‐Mas, R., Buitelaar, J. K., Rommelse, N. N. J., Franke, B., Freitag, C. M., et al. (2015) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2015.1029518 · Cited by 35 · see citing works
Self-citationGan, M., Jiang, P., McLean, P. J., Kanekiyo, T., & Bu, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113237 · Cited by 32 · see citing works
Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis
Li, M., The Swedish Bipolar Study Group, Huang, L., Grigoroiu‐Serbânescu, M., Bergen, S. E., Landén, M., Hultman, C. M., Forstner, A. J., Strohmaier, J., Hecker, J., et al. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9559-6 · Cited by 25 · see citing works
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Wang, X., Kéry, R., & Xiong, Q. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.09.026 · Cited by 21 · see citing works
Genome-Wide Association Study Reveals First Locus for Anorexia Nervosa and Metabolic CorrelationsPreprint
Duncan, L. E., Thornton, L. M., Hinney, A., Daly, M. J., Sullivan, P. F., Zeggini, E., Breen, G. D., & Bulik, C. M. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/088815 · Cited by 13 · see citing works
Alliey‐Rodriguez, N., Grey, T. A., Shafee, R., Padmanabhan, J. L., Tandon, N., Klinger, M., Spring, J., Coppes, L., Reis, K. S., Keshavan, M. S., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/175489 · Cited by 9 · see citing works
Kolb, M., Kurz, S., Schäfer, A., Huse, K., Dietz, A., Wichmann, G., & Birkenmeier, G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180354 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Demontis D, Walters RK, Martin J, et al. Discovery of the first genome-wide significant risk loci for ADHD. Nat Genet 2019;51:63-75.
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Sorted by citations
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Pong, S., Karmacharya, R., Sofman, M., Bishop, J. R., & Lizano, P. L. (2020) · Complex Psychiatry · doi:10.1159/000511552 · Cited by 71 · see citing works
Segatto, M., Tonini, C., Pfrieger, F. W., Trezza, V., & Pallottini, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133317 · Cited by 51 · see citing works
He, Z., Wang, G., Wu, J., Tang, Z., & Luo, M. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111667 · Cited by 49 · see citing works
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Claudio Toma, A., Shaw, A. D., Overs, B. J., Mitchell, P. B., Schofield, P. R., Cooper, A. A., & Fullerton, J. M. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.3382 · Cited by 17 · see citing works
Self-citationAgarwala, S., & Ramachandra, N. B. (2021) · Egyptian Journal of Medical Human Genetics · doi:10.1186/s43042-021-00138-z · Cited by 16 · see citing works
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Lin, J. H. X., de Rezende, V. L., da Costa, M. D. A., de Oliveira, J., & Gonçalves, C. L. (2023) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2023.173522 · Cited by 15 · see citing works
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Afzal, M. J., Tayyaba, S., Ashraf, M. W., Javaid, F., & Bălaş, V. E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-819593-2.00003-0 · Cited by 4 · see citing works
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Muir, A. M., Reich, A., Zou, F., Carere, D. A., Harasink, S. M., Tran, L. H., & McGivern, B. (2024) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2024.100394 · Cited by 2 · see citing works
Pittman, M., Lee, K., Srivastava, D., & Pollard, K. S. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.08.487704 · Cited by 2 · see citing works
Battaglia, R. A., Bolshakova, S., Mazureac, I., Liyanage, D., Pettinari, N. L., Johnson, A., Crouse, E., Habib, S., Flessas, I., Nadig, A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.08.687374 · Cited by 3 · see citing works
Sadeh, T., Baines, R., Black, G., & Manson, F. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1161548 · Cited by 1 · see citing works
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Ma, Y., An, S., Wang, Y., Luo, L., Peng, Z., Wang, X., Cui, Y., Hu, X., Wang, Y., & Zhou, H. (2024) · Research Square · doi:10.21203/rs.3.rs-4317846/v1 · Cited by 1 · see citing works
Fjodorova, M., Noakes, Z., de la Fuente, D. C., Errington, A. C., & Li, M. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.08.463614
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Wang, H., Zhao, S., Chen, Y., Hou, F., Zhu, K., Liu, R., Xiang, Z., Chen, Q., Fan, H., Huang, M., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05962-1
MORRIS, B. J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05954-1
Vellingiri, B., Kinoshita, M., Elangovan, A., Dahiya, B., Kumar, N., Uvarajan, D., Ohara, H., Durairajan, S. S. K., Siama, Z., Narayanasamy, A., et al. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.107087
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Rippert, A. L., Arnadottir, G. A., Bedinger, L., Brunetti‐Pierri, N., Cech, J. N., Chen, X., Chen, Y., Chick, E., Dyack, S., Franchi, M., et al. (2026) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.70261
- Authors
- Torrico, B., Shaw, A. D., Mosca, R., Vivó-Luque, N., Hervás, A., Fernàndez-Castillo, N., Aloy, P., Bayés, M., Fullerton, J. M., Cormand, B., & Toma, C.
- Affiliations
- Institució Catalana de Recerca i Estudis Avançats (ES)
- the Child and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Spain
- From the Departament de Genètica, Microbiologia i Estadística, Universitat de Barcelona, Spain
- the Centro Nacional de Análisis Genómico (CNAG), Barcelona, Spain
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2019-09
- Volume
- 44
- Issue
- 5
- Pages
- 350-359
- ISSN
- 1180-4882 (ISSN-L)
- 1488-2434
- PMC
- PMC6710089
- OpenAlex
- W2971241211
- Cited by
- 34
- References
- 81
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 2 · 2023: 8 · 2022: 2 · 2021: 7 · 2020: 5 · 2019: 2
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion, other-oa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion, other-oa)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Funders
- Fundación Alicia Koplowitz
- Fundació la Marató de TV3 (092010)
- Neuroscience Research Australia
- European Commission (254930)
- Generalitat de Catalunya (2014SGR932)
- Ministerio de Economía y Competitividad (SAF2015-68341-R, BIO2013-48222-R, BIO2016‐77038‐R)
- Universidad de Oviedo
- National Health and Medical Research Council (1066177, 1037196, 1063960)
- Agència de Gestió d'Ajuts Universitaris i de Recerca (2014SGR932)
- FP7 Ideas: European Research Council (614944)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- high-functioning autism, truncating mutations, de novo mutations, LRP1, pleiotropy, schizophrenia, mental illness, splice site mutation, exon skipping, postsynaptic density, FMRP, ultra-rare variants, autism spectrum disorder
- MeSH terms
- Autism Spectrum Disorder, Exome Sequencing, Adolescent, Adult, Alleles, Autistic Disorder, Epilepsy, Family, Female, Humans, Male, Intellectual Disability, Models, Molecular, Mutation, RNA Splicing, Schizophrenia, Spain, Low Density Lipoprotein Receptor-Related Protein-1, Databases, Genetic, Siblings, Gene Regulatory Networks, Young Adult, Genetic Pleiotropy
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.
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