CoChat
Sign Up
Cited by 26Schizophrenia research and treatmentGenetic Associations and EpidemiologyGenetics and Neurodevelopmental Disorders

Multiple genes in a single GWAS risk locus synergistically mediate aberrant synaptic development and function in human neurons

Open access
Zhang, Siwei, Zhang, Hanwen, Forrest, Marc P., Zhou, Yifan, Sun, Xiaotong, Bagchi, Vikram A., Kozlova, Alena, Santos, Marc Dos +7 more·2023·Cell Genomics
DOI 10.1016/j.xgen.2023.100399PMC PMC10504676
Open this paper in CoChat — free account

Abstract

The mechanistic tie between genome-wide association study (GWAS)-implicated risk variants and disease-relevant cellular phenotypes remains largely unknown. Here, using human induced pluripotent stem cell (hiPSC)-derived neurons as a neurodevelopmental model, we identify multiple schizophrenia (SZ) risk variants that display allele-specific open chromatin (ASoC) and are likely to be functional. Editing the strongest ASoC SNP, rs2027349, near vacuolar protein sorting 45 homolog (VPS45) alters the expression of VPS45, lncRNA AC244033.2, and a distal gene, C1orf54. Notably, the transcriptomic changes in neurons are associated with SZ and other neuropsychiatric disorders. Neurons carrying the risk allele exhibit increased dendritic complexity and hyperactivity. Interestingly, individual/combinatorial gene knockdown shows that these genes alter cellular phenotypes in a non-additive synergistic manner. Our study reveals that multiple genes at a single GWAS risk locus mediate a compound effect on neural function, providing a mechanistic link between a non-coding risk variant and disease-related cellular phenotypes.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.xgen.2023.100399

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • eSNP-karyotyping was performed for all cell lines used to eliminate potential chromosomal abnormalities.

    “eSNP-karyotyping was performed for all cell lines used to eliminate potential chromosomal abnormalities, as previously described20,21.”

    From PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia (2025) · cites this paper as [21]

    The STAR★Methods section on experimental models describes checks of pluripotency and CRISPR off-target editing, but does not say that eSNP-karyotyping was performed on all cell lines or used to screen for chromosomal abnormalities. Searches for eSNP-karyotyping, karyotyping, and chromosomal abnormalities found no passage addressing that procedure. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 77

  1. [1]GTEx Consortium The GTEx Consortium atlas of genetic regulatory effects across human tissues Science 369 2020 1318 1330 10.1126/science.aaz1776 32913098 PMC7737656 · DOI · Paper page
  2. [2]Demontis D. Walters R.K. Martin J. Mattheisen M. Als T.D. Agerbo E. Baldursson G. Belliveau R. Bybjerg-Grauholm J. Bækvad-Hansen M. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder Nat. Genet. 51 2019 63 75 10.1038/s41588-018-0269-7 30478444 PMC6481311 · DOI · Paper page
  3. [8]Amiri A. Coppola G. Scuderi S. Wu F. Roychowdhury T. Liu F. Pochareddy S. Shin Y. Safi A. Song L. Transcriptome and epigenome landscape of human cortical development modeled in organoids Science 362 2018 eaat6720 10.1126/science.aat6720 30545853 PMC6426303 · DOI
  4. [9]Li M. Santpere G. Imamura Kawasawa Y. Evgrafov O.V. Gulden F.O. Pochareddy S. Sunkin S.M. Li Z. Shin Y. Zhu Y. Integrative functional genomic analysis of human brain development and neuropsychiatric risks Science 362 2018 eaat7615 10.1126/science.aat7615 30545854 PMC6413317 · DOI · Paper page
  5. [10]Nestler E.J. Hyman S.E. Animal models of neuropsychiatric disorders Nat. Neurosci. 13 2010 1161 1169 10.1038/nn.2647 20877280 PMC3750731 · DOI · Paper page
  6. [12]Schrode N. Ho S.M. Yamamuro K. Dobbyn A. Huckins L. Matos M.R. Cheng E. Deans P.J.M. Flaherty E. Barretto N. Synergistic effects of common schizophrenia risk variants Nat. Genet. 51 2019 1475 1485 10.1038/s41588-019-0497-5 31548722 PMC6778520 · DOI
  7. [14]Forrest M.P. Zhang H. Moy W. McGowan H. Leites C. Dionisio L.E. Xu Z. Shi J. Sanders A.R. Greenleaf W.J. Open chromatin profiling in hiPSC-derived neurons prioritizes functional noncoding psychiatric risk variants and highlights neurodevelopmental loci Cell Stem Cell 21 2017 305 318.e8 10.1016/j.stem.2017.07.008 28803920 PMC5591074 · DOI
  8. [15]Buenrostro J.D. Giresi P.G. Zaba L.C. Chang H.Y. Greenleaf W.J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position Nat. Methods 10 2013 1213 1218 10.1038/nmeth.2688 24097267 PMC3959825 · DOI · Paper page
  9. [16]Wang D. Liu S. Warrell J. Won H. Shi X. Navarro F.C.P. Clarke D. Gu M. Emani P. Yang Y.T. Comprehensive functional genomic resource and integrative model for the human brain Science 362 2018 eaat8464 10.1126/science.aat8464 30545857 PMC6413328 · DOI · Paper page
  10. [18]G.TEx Consortium Genetic effects on gene expression across human tissues Nature 550 2017 204 213 10.1038/nature24277 29022597 PMC5776756 · DOI · Paper page
  11. [19]Zhang Y. Pak C. Han Y. Ahlenius H. Zhang Z. Chanda S. Marro S. Patzke C. Acuna C. Covy J. Rapid single-step induction of functional neurons from human pluripotent stem cells Neuron 78 2013 785 798 10.1016/j.neuron.2013.05.029 23764284 PMC3751803 · DOI · Paper page
  12. [20]Christian K.M. Song H. Ming G.L. Using two- and three-dimensional human iPSC culture systems to model psychiatric disorders Adv. Neurobiol. 25 2020 237 257 10.1007/978-3-030-45493-7_9 32578150 · DOI
  13. [21]De Los Angeles A. Fernando M.B. Hall N.A.L. Brennand K.J. Harrison P.J. Maher B.J. Weinberger D.R. Tunbridge E.M. Induced pluripotent stem cells in psychiatry: an overview and critical perspective Biol. Psychiatry 90 2021 362 372 10.1016/j.biopsych.2021.04.008 34176589 PMC8375580 · DOI
  14. [22]Townsley K.G. Brennand K.J. Huckins L.M. Massively parallel techniques for cataloguing the regulome of the human brain Nat. Neurosci. 23 2020 1509 1521 10.1038/s41593-020-00740-1 33199899 PMC8018778 · DOI
  15. [23]Fernando M.B. Ahfeldt T. Brennand K.J. Modeling the complex genetic architectures of brain disease Nat. Genet. 52 2020 363 369 10.1038/s41588-020-0596-3 32203467 PMC7909729 · DOI
  16. [24]Zhang Y. Liu T. Meyer C.A. Eeckhoute J. Johnson D.S. Bernstein B.E. Nusbaum C. Myers R.M. Brown M. Li W. Liu X.S. Model-based analysis of ChIP-Seq (MACS) Genome Biol. 9 2008 R137 10.1186/gb-2008-9-9-r137 18798982 PMC2592715 · DOI · Paper page
  17. [25]Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci Nature 511 2014 421 427 10.1038/nature13595 25056061 PMC4112379 · DOI · Paper page
  18. [26]O'Brien H.E. Hannon E. Hill M.J. Toste C.C. Robertson M.J. Morgan J.E. McLaughlin G. Lewis C.M. Schalkwyk L.C. Hall L.S. Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders Genome Biol. 19 2018 194 10.1186/s13059-018-1567-1 30419947 PMC6231252 · DOI
  19. [27]Jerber J. Seaton D.D. Cuomo A.S.E. Kumasaka N. Haldane J. Steer J. Patel M. Pearce D. Andersson M. Bonder M.J. Population-scale single-cell RNA-seq profiling across dopaminergic neuron differentiation Nat. Genet. 53 2021 304 312 10.1038/s41588-021-00801-6 33664506 PMC7610897 · DOI
  20. [29]Xie S. Duan J. Li B. Zhou P. Hon G.C. Multiplexed engineering and analysis of combinatorial enhancer activity in single cells Mol. Cell 66 2017 285 299.e5 10.1016/j.molcel.2017.03.007 28416141 · DOI · Paper page
  21. [30]Yeo N.C. Chavez A. Lance-Byrne A. Chan Y. Menn D. Milanova D. Kuo C.C. Guo X. Sharma S. Tung A. An enhanced CRISPR repressor for targeted mammalian gene regulation Nat. Methods 15 2018 611 616 10.1038/s41592-018-0048-5 30013045 PMC6129399 · DOI
  22. [31]Koopmans F. van Nierop P. Andres-Alonso M. Byrnes A. Cijsouw T. Coba M.P. Cornelisse L.N. Farrell R.J. Goldschmidt H.L. Howrigan D.P. SynGO: an evidence-based, expert-curated knowledge base for the synapse Neuron 103 2019 217 234.e4 10.1016/j.neuron.2019.05.002 31171447 PMC6764089 · DOI · Paper page
  23. [32]Dulubova I. Yamaguchi T. Gao Y. Min S.W. Huryeva I. Südhof T.C. Rizo J. How Tlg2p/syntaxin 16 'snares' Vps45 EMBO J. 21 2002 3620 3631 10.1093/emboj/cdf381 12110575 PMC126126 · DOI
  24. [33]McGuire A.L. Gabriel S. Tishkoff S.A. Wonkam A. Chakravarti A. Furlong E.E.M. Treutlein B. Meissner A. Chang H.Y. López-Bigas N. The road ahead in genetics and genomics Nat. Rev. Genet. 21 2020 581 596 10.1038/s41576-020-0272-6 32839576 PMC7444682 · DOI · Paper page
  25. [34]Ang C.E. Ma Q. Wapinski O.L. Fan S. Flynn R.A. Lee Q.Y. Coe B. Onoguchi M. Olmos V.H. Do B.T. The novel lncRNA lnc-NR2F1 is pro-neurogenic and mutated in human neurodevelopmental disorders Elife 8 2019 e41770 10.7554/eLife.41770 30628890 PMC6380841 · DOI
  26. [35]Wang J. Vasaikar S. Shi Z. Greer M. Zhang B. WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit Nucleic Acids Res. 45 2017 W130 W137 10.1093/nar/gkx356 28472511 PMC5570149 · DOI
  27. [37]International Schizophrenia Consortium Purcell S.M. Wray N.R. Stone J.L. Visscher P.M. O'Donovan M.C. Sullivan P.F. Sklar P. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder Nature 460 2009 748 752 10.1038/nature08185 19571811 PMC3912837 · DOI · Paper page
  28. [40]de Leeuw C.A. Mooij J.M. Heskes T. Posthuma D. MAGMA: generalized gene-set analysis of GWAS data PLoS Comput. Biol. 11 2015 e1004219 10.1371/journal.pcbi.1004219 25885710 PMC4401657 · DOI · Paper page
  29. [41]Blizinsky K.D. Diaz-Castro B. Forrest M.P. Schürmann B. Bach A.P. Martin-de-Saavedra M.D. Wang L. Csernansky J.G. Duan J. Penzes P. Reversal of dendritic phenotypes in 16p11.2 microduplication mouse model neurons by pharmacological targeting of a network hub Proc. Natl. Acad. Sci. USA 113 2016 8520 8525 10.1073/pnas.1607014113 27402753 PMC4968749 · DOI · Paper page
  30. [42]Yi F. Danko T. Botelho S.C. Patzke C. Pak C. Wernig M. Südhof T.C. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons Science 352 2016 aaf2669 10.1126/science.aaf2669 26966193 PMC4901875 · DOI · Paper page
  31. [43]Schrode N. Seah C. Deans P.J.M. Hoffman G. Brennand K.J. Analysis framework and experimental design for evaluating synergy-driving gene expression Nat. Protoc. 16 2021 812 840 10.1038/s41596-020-00436-7 33432232 PMC8609447 · DOI
  32. [44]Fromer M. Roussos P. Sieberts S.K. Johnson J.S. Kavanagh D.H. Perumal T.M. Ruderfer D.M. Oh E.C. Topol A. Shah H.R. Gene expression elucidates functional impact of polygenic risk for schizophrenia Nat. Neurosci. 19 2016 1442 1453 10.1038/nn.4399 27668389 PMC5083142 · DOI · Paper page
  33. [45]Song M. Yang X. Ren X. Maliskova L. Li B. Jones I.R. Wang C. Jacob F. Wu K. Traglia M. Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes Nat. Genet. 51 2019 1252 1262 10.1038/s41588-019-0472-1 31367015 PMC6677164 · DOI
  34. [46]Wang Y. Song F. Zhang B. Zhang L. Xu J. Kuang D. Li D. Choudhary M.N.K. Li Y. Hu M. The 3D Genome Browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions Genome Biol. 19 2018 151 10.1186/s13059-018-1519-9 30286773 PMC6172833 · DOI
  35. [47]Barton N.H. Keightley P.D. Understanding quantitative genetic variation Nat. Rev. Genet. 3 2002 11 21 10.1038/nrg700 11823787 · DOI
  36. [48]Moyer C.E. Shelton M.A. Sweet R.A. Dendritic spine alterations in schizophrenia Neurosci. Lett. 601 2015 46 53 10.1016/j.neulet.2014.11.042 25478958 PMC4454616 · DOI
  37. [49]Coyle J.T. Ruzicka W.B. Balu D.T. Fifty Years of Research on Schizophrenia: The Ascendance of the Glutamatergic Synapse Am. J. Psychiatry 177 2020 1119 1128 10.1176/appi.ajp.2020.20101481 33256439 PMC8011846 · DOI
  38. [50]Muhtaseb A.W. Duan J. Modeling common and rare genetic risk factors of neuropsychiatric disorders in human induced pluripotent stem cells Schizophr. Res. 2022 10.1016/j.schres.2022.04.003 PMC9735430 35459617 · DOI
  39. [51]Penzes P. Cahill M.E. Jones K.A. VanLeeuwen J.E. Woolfrey K.M. Dendritic spine pathology in neuropsychiatric disorders Nat. Neurosci. 14 2011 285 293 10.1038/nn.2741 21346746 PMC3530413 · DOI · Paper page
  40. [52]Duan J. Sanders A.R. Gejman P.V. From Schizophrenia Genetics to Disease Biology: Harnessing New Concepts and Technologies J. Psychiatr. Brain Sci. 4 2019 e190014 10.20900/jpbs.20190014 31555746 PMC6760308 · DOI
  41. [53]Ruderfer D.M. Ripke S. McQuillin A. Boocock J. Stahl E.A. Pavlides J.M.W. Mullins N. Charney A.W. Ori A.P. Loohuis L.M.O. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes Cell 173 2018 1705 1715.e16 10.1016/j.cell.2018.05.046 29906448 PMC6432650 · DOI
  42. [54]Ramocki M.B. Zoghbi H.Y. Failure of neuronal homeostasis results in common neuropsychiatric phenotypes Nature 455 2008 912 918 10.1038/nature07457 18923513 PMC2696622 · DOI · Paper page
  43. [55]Landek-Salgado M.A. Faust T.E. Sawa A. Molecular substrates of schizophrenia: homeostatic signaling to connectivity Mol. Psychiatry 21 2016 10 28 10.1038/mp.2015.141 26390828 PMC4684728 · DOI
  44. [57]Gutierrez-Arcelus M. Baglaenko Y. Arora J. Hannes S. Luo Y. Amariuta T. Teslovich N. Rao D.A. Ermann J. Jonsson A.H. Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci Nat. Genet. 52 2020 247 253 10.1038/s41588-020-0579-4 32066938 PMC7135372 · DOI
  45. [58]Pak C. Danko T. Mirabella V.R. Wang J. Liu Y. Vangipuram M. Grieder S. Zhang X. Ward T. Huang Y.W.A. Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons Proc. Natl. Acad. Sci. USA 118 2021 10.1073/pnas.2025598118 e2025598118 PMC8179243 34035170 · DOI
  46. [59]Merkle F.T. Eggan K. Modeling human disease with pluripotent stem cells: from genome association to function Cell Stem Cell 12 2013 656 668 10.1016/j.stem.2013.05.016 23746975 · DOI
  47. [60]Zhang S. Sanders A.R. Duan J. Modeling PTSD neuronal stress responses in a dish Nat. Neurosci. 25 2022 1402 1404 10.1038/s41593-022-01172-9 36266472 PMC9721095 · DOI
  48. [61]Masel J. Siegal M.L. Robustness: mechanisms and consequences Trends Genet. 25 2009 395 403 19717203 PMC2770586
  49. [62]Hockemeyer D. Soldner F. Cook E.G. Gao Q. Mitalipova M. Jaenisch R. A drug-inducible system for direct reprogramming of human somatic cells to pluripotency Cell Stem Cell 3 2008 346 353 10.1016/j.stem.2008.08.014 18786421 PMC4097107 · DOI
  50. [63]Dull T. Zufferey R. Kelly M. Mandel R.J. Nguyen M. Trono D. Naldini L. A third-generation lentivirus vector with a conditional packaging system J. Virol. 72 1998 8463 8471 10.1128/JVI.72.11.8463-8471.1998 9765382 PMC110254 · DOI · Paper page
  51. [64]Bolger A.M. Lohse M. Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data Bioinformatics 30 2014 2114 2120 10.1093/bioinformatics/btu170 24695404 PMC4103590 · DOI · Paper page
  52. [65]Langmead B. Salzberg S.L. Fast gapped-read alignment with Bowtie 2 Nat. Methods 9 2012 357 359 10.1038/nmeth.1923 22388286 PMC3322381 · DOI · Paper page
  53. [66]Li H. Handsaker B. Wysoker A. Fennell T. Ruan J. Homer N. Marth G. Abecasis G. Durbin R. 1000 Genome Project Data Processing Subgroup The Sequence Alignment/Map format and SAMtools Bioinformatics 25 2009 2078 2079 10.1093/bioinformatics/btp352 19505943 PMC2723002 · DOI · Paper page
  54. [67]McKenna A. Hanna M. Banks E. Sivachenko A. Cibulskis K. Kernytsky A. Garimella K. Altshuler D. Gabriel S. Daly M. DePristo M.A. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data Genome Res. 20 2010 1297 1303 10.1101/gr.107524.110 20644199 PMC2928508 · DOI · Paper page
  55. [69]Ramírez F. Ryan D.P. Grüning B. Bhardwaj V. Kilpert F. Richter A.S. Heyne S. Dündar F. Manke T. deepTools2: a next generation web server for deep-sequencing data analysis Nucleic Acids Res. 44 2016 W160 W165 10.1093/nar/gkw257 27079975 PMC4987876 · DOI · Paper page
  56. [70]Dobin A. Davis C.A. Schlesinger F. Drenkow J. Zaleski C. Jha S. Batut P. Chaisson M. Gingeras T.R. STAR: ultrafast universal RNA-seq aligner Bioinformatics 29 2013 15 21 10.1093/bioinformatics/bts635 23104886 PMC3530905 · DOI · Paper page
  57. [71]Stuart T. Butler A. Hoffman P. Hafemeister C. Papalexi E. Mauck W.M. 3rd Hao Y. Stoeckius M. Smibert P. Satija R. Comprehensive integration of single-cell data Cell 177 2019 1888 1902.e21 10.1016/j.cell.2019.05.031 31178118 PMC6687398 · DOI · Paper page
  58. [72]Schneider C.A. Rasband W.S. Eliceiri K.W. NIH Image to ImageJ: 25 years of image analysis Nat. Methods 9 2012 671 675 10.1038/nmeth.2089 22930834 PMC5554542 · DOI · Paper page
  59. [73]Yao Y. Guo W. Zhang S. Yu H. Yan H. Zhang H. Sanders A.R. Yue W. Duan J. Cell type-specific and cross-population polygenic risk score analyses of MIR137 gene pathway in schizophrenia iScience 24 2021 102785 10.1016/j.isci.2021.102785 34308291 PMC8283158 · DOI
  60. [74]Liland K.H. Almøy T. Mevik B.H. Optimal choice of baseline correction for multivariate calibration of spectra Appl. Spectrosc. 64 2010 1007 1016 10.1366/000370210792434350 20828437 · DOI
  61. [75]Victor J.D. Purpura K.P. Nature and precision of temporal coding in visual cortex: a metric-space analysis J. Neurophysiol. 76 1996 1310 1326 10.1152/jn.1996.76.2.1310 8871238 · DOI
  62. [76]Xu J. Carter A.C. Gendrel A.V. Attia M. Loftus J. Greenleaf W.J. Tibshirani R. Heard E. Chang H.Y. Landscape of monoallelic DNA accessibility in mouse embryonic stem cells and neural progenitor cells Nat. Genet. 49 2017 377 386 10.1038/ng.3769 28112738 PMC5357084 · DOI
  63. [77]van de Geijn B. McVicker G. Gilad Y. Pritchard J.K. WASP: allele-specific software for robust molecular quantitative trait locus discovery Nat. Methods 12 2015 1061 1063 10.1038/nmeth.3582 26366987 PMC4626402 · DOI · Paper page
  64. [78]Bernstein B.E. Stamatoyannopoulos J.A. Costello J.F. Ren B. Milosavljevic A. Meissner A. Kellis M. Marra M.A. Beaudet A.L. Ecker J.R. The NIH roadmap epigenomics mapping consortium Nat. Biotechnol. 28 2010 1045 1048 10.1038/nbt1010-1045 20944595 PMC3607281 · DOI · Paper page
  65. [79]Liao Y. Smyth G.K. Shi W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads Nucleic Acids Res. 47 2019 e47 10.1093/nar/gkz114 30783653 PMC6486549 · DOI
  66. [81]Harrow J. Frankish A. Gonzalez J.M. Tapanari E. Diekhans M. Kokocinski F. Aken B.L. Barrell D. Zadissa A. Searle S. GENCODE: the reference human genome annotation for The ENCODE Project Genome Res. 22 2012 1760 1774 10.1101/gr.135350.111 22955987 PMC3431492 · DOI · Paper page
  67. [82]Bray N.L. Pimentel H. Melsted P. Pachter L. Near-optimal probabilistic RNA-seq quantification Nat. Biotechnol. 34 2016 525 527 10.1038/nbt.3519 27043002 · DOI · Paper page
  68. [83]Robinson M.D. McCarthy D.J. Smyth G.K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Bioinformatics 26 2010 139 140 10.1093/bioinformatics/btp616 19910308 PMC2796818 · DOI · Paper page
  69. [84]Mayfield R.D. Harris R.A. Schuckit M.A. Genetic factors influencing alcohol dependence Br. J. Pharmacol. 154 2008 275 287 10.1038/bjp.2008.88 18362899 PMC2442454 · DOI · Paper page
  70. [85]Gaiteri C. Sibille E. Differentially expressed genes in major depression reside on the periphery of resilient gene coexpression networks Front. Neurosci. 5 2011 95 10.3389/fnins.2011.00095 21922000 PMC3166821 · DOI
  71. [86]Nagel M. Jansen P.R. Stringer S. Watanabe K. de Leeuw C.A. Bryois J. Savage J.E. Hammerschlag A.R. Skene N.G. Muñoz-Manchado A.B. Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways Nat. Genet. 50 2018 920 927 10.1038/s41588-018-0151-7 29942085 · DOI
  72. [87]Stahl E.A. Breen G. Forstner A.J. McQuillin A. Ripke S. Trubetskoy V. Mattheisen M. Wang Y. Coleman J.R.I. Gaspar H.A. Genome-wide association study identifies 30 loci associated with bipolar disorder Nat. Genet. 51 2019 793 803 10.1038/s41588-019-0397-8 31043756 PMC6956732 · DOI · Paper page
  73. [88]Zhou Z. Yuan Q. Mash D.C. Goldman D. Substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol Proc. Natl. Acad. Sci. USA 108 2011 6626 6631 10.1073/pnas.1018514108 21464311 PMC3081016 · DOI
  74. [89]Liu J.Z. van Sommeren S. Huang H. Ng S.C. Alberts R. Takahashi A. Ripke S. Lee J.C. Jostins L. Shah T. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations Nat. Genet. 47 2015 979 986 10.1038/ng.3359 26192919 PMC4881818 · DOI · Paper page
  75. [90]Pardiñas A.F. Holmans P. Pocklington A.J. Escott-Price V. Ripke S. Carrera N. Legge S.E. Bishop S. Cameron D. Hamshere M.L. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection Nat. Genet. 50 2018 381 389 10.1038/s41588-018-0059-2 29483656 PMC5918692 · DOI · Paper page
  76. [91]Bayés A. van de Lagemaat L.N. Collins M.O. Croning M.D.R. Whittle I.R. Choudhary J.S. Grant S.G.N. Characterization of the proteome, diseases and evolution of the human postsynaptic density Nat. Neurosci. 14 2011 19 21 10.1038/nn.2719 21170055 PMC3040565 · DOI · Paper page
  77. [92]Zhang Y. Parmigiani G. Johnson W.E. ComBat-seq: batch effect adjustment for RNA-seq count data NAR Genom. Bioinform. 2 2020 lqaa078 10.1093/nargab/lqaa078 33015620 PMC7518324 · DOI · Paper page

Cited by

Sorted by citations

  • PICALM Alzheimer’s risk allele causes aberrant lipid droplets in microglia

    Kozlova, A., Zhang, S., Sudwarts, A., Zhang, H., Smirnou, S., Byeon, S. K., Thapa, C., Sun, X., Stephenson, K., Zhao, X., et al. (2025) · Nature · doi:10.1038/s41586-025-09486-x · Cited by 53 · see citing works

    “…identify functional LOAD GWAS risk variants, we performed an assay for transposase-accessible chromatin using sequencing (ATAC–seq) and ascertained the allelic imbalance of chromatin accessibility (that is, ASoC) 20,21 at heterozygous LOAD-risk single-nucleotide polymorphism (SNP) sites (Fig.”
    InfluentialSelf-citation

Authors
Zhang, S., Zhang, H., Forrest, M. P., Zhou, Y., Sun, X., Bagchi, V. A., Kozlova, A., Santos, M. D., Piguel, N. H., Dionisio, L. E., Sanders, A. R., Pang, Z. P., He, X., Penzes, P., & Duan, J.
Affiliations
  • Endeavor Health (US)
  • Northwestern University (US)
  • University of Chicago (US)
  • Rutgers, The State University of New Jersey (US)
Corresponding author
Duan, Jubao
ORCID
Venue
Cell Genomics
Publisher
Elsevier BV
Published
2023-09
Volume
3
Issue
9
Pages
100399
ISSN
2666-979X (ISSN-L)
DOI
10.1016/j.xgen.2023.100399
PMC
PMC10504676
OpenAlex
W4386226597
Cited by
26
References
14
Citations by year
2026: 6 · 2025: 8 · 2024: 9 · 2023: 2 · 2022: 1
FWCI
5.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Genomics (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01AA023797, R01AG063175, R01MH097216, R01MH106575, R01MH110531, R01MH116281, R01MH125528)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
schizophrenia, VPS45, synaptic development, dendritic complexity, neuronal hyperactivity, non-coding variants, hiPSC-derived neurons, neurodevelopmental disorders

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