CoChat
Sign Up
Cited by 239Genetic Associations and EpidemiologySingle-cell and spatial transcriptomicsBioinformatics and Genomic Networks

Identifying disease-critical cell types and cellular processes by integrating single-cell RNA-sequencing and human genetics

Open access
Jagadeesh, Karthik A., Dey, Kushal K., Montoro, Daniel T., Mohan, Rahul, Gazal, Steven, Engreitz, Jesse M., Xavier, Ramnik J., Price, Alkes L. +1 more·2022·Nature Genetics
DOI 10.1038/s41588-022-01187-9PMC PMC9910198
Open this paper in CoChat — free accountOpen PDF

Abstract

Genome-wide association studies provide a powerful means of identifying loci and genes contributing to disease, but in many cases, the related cell types/states through which genes confer disease risk remain unknown. Deciphering such relationships is important for identifying pathogenic processes and developing therapeutics. In the present study, we introduce sc-linker, a framework for integrating single-cell RNA-sequencing, epigenomic SNP-to-gene maps and genome-wide association study summary statistics to infer the underlying cell types and processes by which genetic variants influence disease. The inferred disease enrichments recapitulated known biology and highlighted notable cell-disease relationships, including γ-aminobutyric acid-ergic neurons in major depressive disorder, a disease-dependent M-cell program in ulcerative colitis and a disease-specific complement cascade process in multiple sclerosis. In autoimmune disease, both healthy and disease-dependent immune cell-type programs were associated, whereas only disease-dependent epithelial cell programs were prominent, suggesting a role in disease response rather than initiation. Our framework provides a powerful approach for identifying the cell types and cellular processes by which genetic variants influence disease.

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 · 10.1038/s41588-022-01187-9

Cites

19 of 19 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?

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: 105

  1. [2]Visscher PM 10 Years of GWAS Discovery: Biology, Function, and Translation. Am. J. Hum. Genet 101, 5 (2017). 28686856 PMC5501872
  2. [3]Buniello A The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 47, D1005– D1012 (2019). 30445434 PMC6323933
  3. [6]Shendure J, Findlay GM & Snyder MW Genomic medicine -- progress, pitfalls, and promise. Cell 177, 45– 57 (2019). 30901547 PMC6531313
  4. [7]Zeggini E, Gloyn AL, Barton AC & Wain LV Translational genomics and precision medicine: Moving from the lab to the clinic. Science 365, 1409– 1413 (2019). 31604268
  5. [8]Hekselman I & Yeger-Lotem E Mechanisms of tissue and cell-type specificity in heritable traits and diseases. Nat. Rev. Genet 21, 137– 150 (2020). 31913361
  6. [9]Trynka G Chromatin marks identify critical cell types for fine mapping complex trait variants. Nat. Genet 45, (2013). PMC3826950 23263488
  7. [10]Pickrell JK Joint Analysis of Functional Genomic Data and Genome-wide Association Studies of 18 Human Traits. Am. J. Hum. Genet 95, 126 (2014). PMC3980523 24702953
  8. [11]Finucane HK Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet 47, 1228 (2015). 26414678 PMC4626285
  9. [12]Zhou J Deep learning sequence-based ab initio prediction of variant effects on expression and disease risk. Nat. Genet 50, 1171– 1179 (2018). 30013180 PMC6094955
  10. [13]Zhu X & Stephens M Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes. Nat. Commun 9, (2018). PMC6195536 30341297
  11. [14]Wang Q A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data. Nat. Neurosci 22, 691 (2019). 30988527 PMC6646046
  12. [15]Fang H A genetics-led approach defines the drug target landscape of 30 immune-related traits. Nat. Genet 51, 1082 (2019). 31253980 PMC7124888
  13. [17]Ongen H Estimating the causal tissues for complex traits and diseases. Nat. Genet 49, 1676– 1683 (2017). 29058715
  14. [18]Finucane HK Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet 50, 621 (2018). 29632380 PMC5896795
  15. [19]Ernst J Systematic analysis of chromatin state dynamics in nine human cell types. Nature 473, 43 (2011). 21441907 PMC3088773
  16. [21]Liu Y, Sarkar A, Kheradpour P, Ernst J & Kellis M Evidence of reduced recombination rate in human regulatory domains. Genome Biol. 18, 193 (2017). 29058599 PMC5651596
  17. [22]Fulco CP Activity-by-Contact model of enhancer-promoter regulation from thousands of CRISPR perturbations. Nat. Genet 51, 1664 (2019). 31784727 PMC6886585
  18. [23]Nasser J Genome-wide enhancer maps link risk variants to disease genes. Nature 593, 238– 243 (2021). 33828297 PMC9153265
  19. [24]Tanay A & Regev A Scaling single-cell genomics from phenomenology to mechanism. Nature 541, 331– 338 (2017). 28102262 PMC5438464
  20. [26]Travaglini KJ A molecular cell atlas of the human lung from single cell RNA sequencing. bioRxiv 742320 (2020) doi: 10.1101/742320. PMC7704697 33208946 · DOI
  21. [29]Habermann AC Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci. Adv 6, (2020). PMC7439444 32832598
  22. [30]Mathys H Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332 (2019). 31042697 PMC6865822
  23. [32]Montoro DT A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature 560, 319– 324 (2018). 30069044 PMC6295155
  24. [33]Peng Y-R Molecular Classification and Comparative Taxonomics of Foveal and Peripheral Cells in Primate Retina. Cell 176, 1222– 1237.e22 (2019). 30712875 PMC6424338
  25. [34]Smillie CS Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell 178, 714– 730.e22 (2019). 31348891 PMC6662628
  26. [35]Watanabe K, Umićević Mirkov M, de Leeuw CA, van den Heuvel MP & Posthuma D Genetic mapping of cell type specificity for complex traits. Nat. Commun 10, 3222 (2019). 31324783 PMC6642112
  27. [36]Bryois J Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease. Nat. Genet 52, 482– 493 (2020). 32341526 PMC7930801
  28. [37]Corces MR Single-cell epigenomic analyses implicate candidate causal variants at inherited risk loci for Alzheimer’s and Parkinson’s diseases. Nat. Genet 52, 1158– 1168 (2020). 33106633 PMC7606627
  29. [38]Drokhlyansky E The Human and Mouse Enteric Nervous System at Single-Cell Resolution. Cell 182, 1606– 1622.e23 (2020). 32888429 PMC8358727
  30. [40]Gazal S Linkage disequilibrium dependent architecture of human complex traits shows action of negative selection. Nat. Genet 49, 1421 (2017). 28892061 PMC6133304
  31. [41]Gazal S, Marquez-Luna C, Finucane HK & Price AL Reconciling S-LDSC and LDAK functional enrichment estimates. Nat. Genet 51, 1202 (2019). 31285579 PMC7006477
  32. [43]Stewart BJ Spatio-temporal immune zonation of the human kidney. Science 365, 1461 (2019). 31604275 PMC7343525
  33. [44]Muus C Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells. bioRxiv 2020.04.19.049254 (2020) doi: 10.1101/2020.04.19.049254. · DOI
  34. [45]Cheng JB Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution. Cell Rep. 25, 871 (2018). 30355494 PMC6367716
  35. [47]Braga F A cellular census of human lungs identifies novel cell states in health and in asthma. Nat. Med 25, (2019). 31209336
  36. [48]Liao M Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med 26, 842– 844 (2020). 32398875
  37. [49]Ulirsch JC Interrogation of human hematopoiesis at single-cell and single-variant resolution. Nat. Genet 51, 683– 693 (2019). 30858613 PMC6441389
  38. [51]Biedermann T, Skabytska Y, Kaesler S & Volz T Regulation of T Cell Immunity in Atopic Dermatitis by Microbes: The Yin and Yang of Cutaneous Inflammation. Front. Immunol 6, (2015). PMC4500098 26217343
  39. [52]Hennino A Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions. J. Immunol 178, 5571– 5577 (2007). 17442939
  40. [53]Thériault P, ElAli A & Rivest S The dynamics of monocytes and microglia in Alzheimer’s disease. Alzheimers Res. Ther 7, (2015). PMC4397873 25878730
  41. [54]Nuyts AH, Lee WP, Bashir-Dar R, Berneman ZN & Cools N Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies? Mult. Scler. Houndmills Basingstoke Engl 19, 995– 1002 (2013). 23369893
  42. [55]Haschka D Expansion of Neutrophils and Classical and Nonclassical Monocytes as a Hallmark in Relapsing-Remitting Multiple Sclerosis. Front. Immunol 11, 594 (2020). 32411125 PMC7202453
  43. [56]Momeni A Fingolimod and changes in hematocrit, hemoglobin and red blood cells of patients with multiple sclerosis. Am. J. Clin. Exp. Immunol 8, 27– 31 (2019). 31497380 PMC6726974
  44. [57]Yeung M Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-γδ expression. Gut 47, 215– 227 (2000). 10896913 PMC1728017
  45. [58]Mouly E The Ets-1 transcription factor controls the development and function of natural regulatory T cells. J. Exp. Med 207, 2113 (2010). 20855499 PMC2947068
  46. [59]Mayassi T Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease. Cell 176, 967– 981.e19 (2019). 30739797 PMC6667191
  47. [60]Pandey A Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat. Immunol 1, 59– 64 (2000). 10881176
  48. [61]Gao P-S Genetic Variants in TSLP are Associated with Atopic Dermatitis and Eczema Herpeticum. J. Allergy Clin. Immunol 125, 1403– 1407.e4 (2010). 20466416 PMC2925504
  49. [62]Altin JA Ndfip1 mediates peripheral tolerance to self and exogenous antigen by inducing cell cycle exit in responding CD4+ T cells. Proc. Natl. Acad. Sci 111, 2067– 2074 (2014). 24520172 PMC3926078
  50. [63]Yip KH The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation. Nat. Commun 7, (2016). PMC5095291 27786273
  51. [65]Efthymiou AG & Goate AM Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk. Mol. Neurodegener 12, (2017). PMC5446752 28549481
  52. [66]Luscher B, Shen Q & Sahir N The GABAergic Deficit Hypothesis of Major Depressive Disorder. Mol. Psychiatry 16, 383– 406 (2011). 21079608 PMC3412149
  53. [68]Li L Disruption of TCF4 regulatory networks leads to abnormal cortical development and mental disabilities. Mol. Psychiatry 24, (2019). PMC11019556 30705426
  54. [69]Mbarek H Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder. Twin Res. Hum. Genet. Off. J. Int. Soc. Twin Stud 20, (2017). 28540843
  55. [70]Ciarimboli G Proximal Tubular Secretion of Creatinine by Organic Cation Transporter OCT2 in Cancer Patients. Clin. Cancer Res 18, 1101 (2012). 22223530 PMC3288323
  56. [71]Zhang X Tubular secretion of creatinine and kidney function: an observational study. BMC Nephrol. 21, (2020). PMC7104490 32228497
  57. [72]Cui C, J K, I L, U B & D K Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J. Biol. Chem 276, (2001). 11134001
  58. [74]Barth AS & Tomaselli GF Cardiac metabolism and arrhythmias. Circ. Arrhythm. Electrophysiol 2, 327– 335 (2009). 19808483 PMC2744981
  59. [75]Yamazaki T & Mukouyama Y Tissue Specific Origin, Development, and Pathological Perspectives of Pericytes. Front. Cardiovasc. Med 5, (2018). PMC6030356 29998128
  60. [76]Deckers J, Hammad H & Hoste E Langerhans Cells: Sensing the Environment in Health and Disease. Front. Immunol 9, (2018). PMC5799717 29449841
  61. [77]Hsieh KH, Chou CC & Huang SF Interleukin 2 therapy in severe atopic dermatitis. J. Clin. Immunol 11, 22– 28 (1991). 1673687
  62. [78]Kuleshov MV Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 44, W90– 97 (2016). 27141961 PMC4987924
  63. [79]Attie AD & Scherer PE Adipocyte metabolism and obesity. J. Lipid Res 50, S395– S399 (2009). 19017614 PMC2674728
  64. [80]Heneka MT An immune-cell signature marks the brain in Alzheimer’s disease. Nature 577, 322– 323 (2020). 31937952
  65. [81]Rossi S Inflammation inhibits GABA transmission in multiple sclerosis. Mult. Scler. Houndmills Basingstoke Engl 18, 1633– 1635 (2012). 22419673
  66. [82]Cannella B The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A 95, 10100– 10105 (1998). 9707607 PMC21468
  67. [83]Horstmann L Inflammatory demyelination induces glia alterations and ganglion cell loss in the retina of an experimental autoimmune encephalomyelitis model. J. Neuroinflammation 10, 120 (2013). 24090415 PMC3851328
  68. [84]Healy LM MerTK-mediated regulation of myelin phagocytosis by macrophages generated from patients with MS. Neurol. Neuroimmunol. Neuroinflammation 4, (2017). PMC5777663 29379818
  69. [86]Hemonnot A-L, Hua J, Ulmann L & Hirbec H Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities. Front. Aging Neurosci 11, (2019). PMC6730262 31543810
  70. [87]Cromer WE, Mathis JM, Granger DN, Chaitanya GV & Alexander JS Role of the endothelium in inflammatory bowel diseases. World J. Gastroenterol. WJG 17, 578– 593 (2011). 21350707 PMC3040330
  71. [89]Graham DB & Xavier RJ Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature 578, 527– 539 (2020). 32103191 PMC7871366
  72. [90]Bianco AM, Girardelli M & Tommasini A Genetics of inflammatory bowel disease from multifactorial to monogenic forms. World J. Gastroenterol 21, 12296– 12310 (2015). 26604638 PMC4649114
  73. [92]Jin X In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes. Science 370, (2020). PMC7985844 33243861
  74. [1]Travaglini KJ A molecular cell atlas of the human lung from single cell RNA sequencing. bioRxiv 742320 (2020) doi: 10.1101/742320. PMC7704697 33208946 · DOI
  75. [2]Zheng GXY Massively parallel digital transcriptional profiling of single cells. Nat. Commun 8, (2017). PMC5241818 28091601
  76. [4]Sunkin SM Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system. Nucleic Acids Res. 41, D996 (2013). 23193282 PMC3531093
  77. [5]Stewart BJ Spatio-temporal immune zonation of the human kidney. Science 365, 1461 (2019). 31604275 PMC7343525
  78. [6]Muus C Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells. bioRxiv 2020.04.19.049254 (2020) doi: 10.1101/2020.04.19.049254. · DOI
  79. [7]Schirmer L Neuronal vulnerability and multilineage diversity in multiple sclerosis. Nature 573, 75 (2019). 31316211 PMC6731122
  80. [8]Mathys H Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332 (2019). 31042697 PMC6865822
  81. [9]Smillie CS Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell 178, 714– 730.e22 (2019). 31348891 PMC6662628
  82. [10]Habermann AC Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci. Adv 6, (2020). PMC7439444 32832598
  83. [11]Tucker N Transcriptional and Cellular Diversity of the Human Heart. Circulation (2020) doi: 10.1161/CIRCULATIONAHA.119.045401. PMC7666104 32403949 · DOI · Paper page
  84. [12]Braga F A cellular census of human lungs identifies novel cell states in health and in asthma. Nat. Med 25, (2019). 31209336
  85. [13]Liao M Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat. Med 26, 842– 844 (2020). 32398875
  86. [14]Cheng JB Transcriptional Programming of Normal and Inflamed Human Epidermis at Single-Cell Resolution. Cell Rep. 25, 871 (2018). 30355494 PMC6367716
  87. [16]Korsunsky I Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289– 1296 (2019). 31740819 PMC6884693
  88. [17]Traag VA, Waltman L & van Eck NJ From Louvain to Leiden: guaranteeing well-connected communities. Sci. Rep 9, 5233 (2019). 30914743 PMC6435756
  89. [19]Fang H A genetics-led approach defines the drug target landscape of 30 immune-related traits. Nat. Genet 51, 1082 (2019). 31253980 PMC7124888
  90. [20]Lee DD & Seung HS Algorithms for non-negative matrix factorization. in Proceedings of the 13th International Conference on Neural Information Processing Systems 535– 541 (MIT Press, 2000).
  91. [22]Liu Y, Sarkar A, Kheradpour P, Ernst J & Kellis M Evidence of reduced recombination rate in human regulatory domains. Genome Biol. 18, 193 (2017). 29058599 PMC5651596
  92. [23]Kundaje A Integrative analysis of 111 reference human epigenomes. Nature 518, 317– 330 (2015). 25693563 PMC4530010
  93. [24]Fulco CP Activity-by-Contact model of enhancer-promoter regulation from thousands of CRISPR perturbations. Nat. Genet 51, 1664 (2019). 31784727 PMC6886585
  94. [25]Nasser J Genome-wide maps of enhancer regulation connect risk variants to disease genes. bioRxiv 2020.09.01.278093 (2020) doi: 10.1101/2020.09.01.278093. · DOI
  95. [26]Dey KK Unique contribution of enhancer-driven and master-regulator genes to autoimmune disease revealed using functionally informed SNP-to-gene linking strategies. bioRxiv 2020.09.02.279059 (2020) doi: 10.1101/2020.09.02.279059. · DOI
  96. [27]Finucane HK Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet 50, 621 (2018). 29632380 PMC5896795
  97. [28]Zhu X & Stephens M Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes. Nat. Commun 9, (2018). PMC6195536 30341297
  98. [29]Gazal S Linkage disequilibrium dependent architecture of human complex traits shows action of negative selection. Nat. Genet 49, 1421 (2017). 28892061 PMC6133304
  99. [30]Gazal S, Marquez-Luna C, Finucane HK & Price AL Reconciling S-LDSC and LDAK functional enrichment estimates. Nat. Genet 51, 1202 (2019). 31285579 PMC7006477
  100. [31]Finucane HK Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet 47, 1228 (2015). 26414678 PMC4626285
  101. [32]Hormozdiari F Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits. Nat. Genet 50, 1041 (2018). 29942083 PMC6030458
  102. [34]van de Geijn B Annotations capturing cell type-specific TF binding explain a large fraction of disease heritability. Hum. Mol. Genet 29, 1057– 1067 (2020). 31595288 PMC7206853
  103. [35]The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur. J. Hum. Genet 1– 4 (2020) doi: 10.1038/s41431-020-0636-6. PMC7220587 32404885 · DOI
  104. [36]Ulirsch JC Interrogation of human hematopoiesis at single-cell and single-variant resolution. Nat. Genet 51, 683– 693 (2019). 30858613 PMC6441389
  105. [37]Chen M-H Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations. Cell 182, 1198– 1213.e14 (2020). 32888493 PMC7480402

Cited by

Sorted by citations

Authors
Jagadeesh, K. A., Dey, K. K., Montoro, D. T., Mohan, R., Gazal, S., Engreitz, J. M., Xavier, R. J., Price, A. L., & Regev, A.
Affiliations
  • Broad Institute (US)
  • Harvard University (US)
Corresponding author
  • Jagadeesh, Karthik A.
  • Dey, Kushal K.
  • Price, Alkes L.
  • Regev, Aviv
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2022-09-29
Volume
54
Issue
10
Pages
1479-1492
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/s41588-022-01187-9
PMC
PMC9910198
OpenAlex
W4297977428
Cited by
239
References
19
Citations by year
2026: 48 · 2025: 70 · 2024: 65 · 2023: 46 · 2022: 10
FWCI
30.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (HG009379, MH101244, F32)
  • Howard Hughes Medical Institute (HHMI)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
single-cell RNA sequencing, genome-wide association study, genetic variants, cell types, cellular processes, disease risk, major depressive disorder, ulcerative colitis, multiple sclerosis, autoimmune disease, M cells, complement system, GABAergic neurons, epithelial cells
MeSH terms
Human Genetics, Depressive Disorder, Major, Major Depressive Disorder, gamma-Aminobutyric Acid, Humans, RNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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