Allele-Specific Methylation of SPDEF: A Novel Moderator of Psychosocial Stress and Substance Abuse
Open accessAbstract
OBJECTIVE: Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population. METHODS: A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study. RESULTS: Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use. CONCLUSIONS: Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
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
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?
A large EWAS in 1,287 adolescents found a post-hoc significant positive correlation of a CpG island within the promoter of SPDEF with the frequency of negative stressful life events in the past year.
“A large EWAS in 1,287 adolescents found post-hoc significant positive correlation of a CpG island within the promoter of the SAM pointed domain-containing Ets transcription factor (SPDEF, chromosomal location 6p21.31) with the frequency of negative stressful life events in the past year (Tay et al., 2019).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Tay et al., 2019
The Results section, “Association of Differentially Methylated Regions With Frequency of Stressful Life Events” (page not supplied), reports a genome-wide significant region in the 5′ region of SPDEF and positive, significant correlations at two CpG sites in 1,287 adolescents. The Methods specify that the negative life events occurred in the past year. Our copy does not identify the region as a CpG island or describe the correlation finding as post-hoc; its stated post-hoc step was quality control. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA significant interaction effect between the frequency of stressful life events in the past year and increased methylation was discerned to result in a higher incidence of lifetime binge drinking behavior.
“Moreover, a significant interaction effect between the frequency of stressful life events in the past year and increased methylation was discerned to result in an higher incidence of lifetime binge drinking behavior.”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Tay et al., 2019
The Questionnaire and Interview Data section says stressful events were measured over the past year and binge drinking was measured as lifetime frequency. The results report a significant interaction between stressful-event frequency and cg01395541 methylation for lifetime binge drinking (p=0.023). They describe methylation as moderating an association, however, rather than showing that the interaction resulted in a higher incidence of binge drinking. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA methylation-expression quantitative trait loci (eQTL) analysis suggested that methylation would lead to expression changes in multiple trans-genes enriched for genes previously linked to opioid-related disorders, alcoholism and tobacco use, providing converging evidence for a novel epigenetic risk marker of adolescent substance abuse integrating the molecular effects of psychosocial stress.
“A methylation-expression quantitative trait loci (eQTL) analysis suggested that methylation would lead to expression changes in multiple trans-genes enriched for genes previously linked to opioid-related disorders, alcoholism and tobacco use, providing converging evidence for a novel epigenetic risk marker of adolescent substance abuse integrating the molecular effects of psychosocial stress (Tay”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Tay et al., 2019
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Jaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325 · see citing works
Aryee, M. J., Jaffe, A. E., Bravo, H. C., Ladd‐Acosta, C., Feinberg, A. P., Hansen, K. D., & Irizarry, R. A. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu049 · Cited by 4,423 · see citing works
Why do many psychiatric disorders emerge during adolescence?
Paus, T., Keshavan, M., & Giedd, J. N. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2513 · Cited by 3,123 · see citing works
Self-citationMatrix eQTL: ultra fast eQTL analysis via large matrix operations
Shabalin, A. A. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts163 · Cited by 1,694 · see citing works
For Better <i>and</i> For Worse: Differential Susceptibility to Environmental Influences
Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2007) · Current Directions in Psychological Science · doi:10.1111/j.1467-8721.2007.00525.x · Cited by 1,515 · see citing works
Is there a common molecular pathway for addiction?
Nestler, E. J. (2005) · Nature Neuroscience · doi:10.1038/nn1578 · Cited by 1,388 · see citing works
Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies
Jaffe, A. E., Murakami, P. N., Lee, H.-J., Leek, J. T., Fallin, M. D., Feinberg, A. P., & Irizarry, R. A. (2012) · International Journal of Epidemiology · doi:10.1093/ije/dyr238 · Cited by 687 · see citing works
The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology
Schumann, G., Loth, E., Banaschewski, T., Barbot, A., Barker, G. J., Büchel, C., Conrod, P., Dalley, J. W., Flor, H., Gallinat, J., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.4 · Cited by 618 · see citing works
Self-citationAnalysing and interpreting DNA methylation data
Bock, C. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3273 · Cited by 580 · see citing works
Wang, Y., Song, F., Zhang, B., Zhang, L., Xu, J., Kuang, D., Li, D., Choudhary, M. N. K., Li, Y., Hu, M., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1519-9 · Cited by 552 · see citing works
Hannon, E., Lunnon, K., Schalkwyk, L., & Mill, J. (2015) · Epigenetics · doi:10.1080/15592294.2015.1100786 · Cited by 455 · see citing works
A multidimensional assessment of stressful life events among adolescents: Derivation and correlates
Newcomb, M. D., Huba, G. J., & Bentler, P. M. (1981) · Journal of Health and Social Behavior · doi:10.2307/2136681 · Cited by 359 · see citing works
The Psychiatric GWAS Consortium: Big Science Comes to Psychiatry
Sullivan, P. F. (2010) · Neuron · doi:10.1016/j.neuron.2010.10.003 · Cited by 285 · see citing works
GWAS identifies four novel eosinophilic esophagitis loci
Abou‐Sleiman, P. M., Wang, M., Cianferoni, A., Aceves, S. S., Gonsalves, N. P., Nadeau, K. C., Bredenoord, A. J., Furuta, G. T., Spergel, J. M., & Hakonarson, H. H. (2014) · Nature Communications · doi:10.1038/ncomms6593 · Cited by 241 · see citing works
Quertemont, É. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001497 · Cited by 176 · see citing works
Environmental stress and psychiatric illness
Agid, O., Kohn, Y., & Lerer, B. (2000) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(00)89046-0 · Cited by 169 · see citing works
Epigenetics of Stress, Addiction, and Resilience: Therapeutic Implications
Cadet, J. L. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-9040-y · Cited by 149 · see citing works
OPRM1 SNP (A118G): Involvement in disease development, treatment response, and animal models
Mague, S. D., & Blendy, J. A. (2010) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.12.016 · Cited by 136 · see citing works
Tyrka, A. R., Parade, S. H., Welch, E. S., Ridout, K. K., Price, L. H., Marsit, C., Philip, N. S., & Carpenter, L. L. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.112 · Cited by 135 · see citing works
Barker, E. D., Walton, E., & Cecil, C. A. M. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12782 · Cited by 134 · see citing works
Self-citationTaqi, M. M., Bazov, I., Watanabe, H., Sheedy, D. L., Harper, C. G., Alkass, K., Druid, H., Wentzel, P., Nyberg, F., Yakovleva, T., et al. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00323.x · Cited by 132 · see citing works
Self-citationCpG island methylation pattern in different human tissues and its correlation with gene expression
Fan, S., & Zhang, X. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.04.023 · Cited by 125 · see citing works
Sensory and motor aspects of addiction
Yalachkov, Y., Kaiser, J., & Naumer, M. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.09.015 · Cited by 117 · see citing works
Gender differences in neural correlates of stress-induced anxiety
Seo, D., Ahluwalia, A., Potenza, M. N., & Sinha, R. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23926 · Cited by 114 · see citing works
Roessler, J., Ammerpohl, O., Gutwein, J., Hasemeier, B., Anwar, S. L., Kreipe, H., & Lehmann, U. (2012) · BMC Research Notes · doi:10.1186/1756-0500-5-210 · Cited by 112 · see citing works
The Neurobiology of Intervention and Prevention in Early Adversity
Fisher, P. A., Beauchamp, K. G., Roos, L. E., Noll, L. K., Flannery, J., & Delker, B. C. (2015) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032814-112855 · Cited by 93 · see citing works
Current and Future Prospects for Epigenetic Biomarkers of Substance Use Disorders
Andersen, A. M., Dogan, M. V., Beach, S. R. H., & Philibert, R. A. (2015) · Genes · doi:10.3390/genes6040991 · Cited by 85 · see citing works
Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence
Casement, M. D., Shaw, D. S., Sitnick, S. L., Musselman, S. C., & Forbes, E. E. (2015) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu061 · Cited by 82 · see citing works
Daca‐Roszak, P., Pfeifer, A., Żebracka‐Gala, J., Rusinek, D., Szybińska, A., Jarząb, B., Witt, M., & Ziętkiewicz, E. (2015) · BMC Genomics · doi:10.1186/s12864-015-2202-0 · Cited by 82 · see citing works
Transdiagnostic brain responses to disorder-related threat across four psychiatric disorders
Feldker, K., Heitmann, C. Y., Neumeister, P., Tupak, S. V., Schrammen, E., Moeck, R., Zwitserlood, P., Bruchmann, M., & Straube, T. (2016) · Psychological Medicine · doi:10.1017/s0033291716002634 · Cited by 43 · see citing works
Gene expression profiling in porcine maternal infanticide: A model for puerperal psychosis
Quilter, C. R., Gilbert, C. L., Oliver, G. L., Jafer, O., Furlong, R. A., Blott, S. C., Wilson, A. E., Sargent, C. A., Mileham, A. J., & Affara, N. A. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30734 · Cited by 40 · see citing works
Tomasi, D. G., Wang, G.-J., & Volkow, N. D. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.93 · Cited by 22 · see citing works
Parira, T., Laverde, A., & Agudelo, M. (2017) · Journal of Alcoholism and Drug Dependence · doi:10.4172/2329-6488.1000259 · Cited by 16 · see citing works
Signatures of prostate-derived Ets factor (PDEF) in cancer
Mahajan, N. (2016) · Tumor Biology · doi:10.1007/s13277-016-5326-1 · Cited by 13 · see citing works
TLR4 Methylation Moderates the Relationship Between Alcohol Use Severity and Gray Matter Loss
Karoly, H. C., Thayer, R. E., Hagerty, S. L., & Hutchison, K. E. (2017) · Journal of Studies on Alcohol and Drugs · doi:10.15288/jsad.2017.78.696 · Cited by 7 · see citing works
Flagged first, then by citations
1 of the 37 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Dr. Banaschewski has served as an adviser or consultant for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, and Shire; he has received conference support or speaking fees from Lilly, Medice, Novartis, and Shire; he has participated in clinical trials conducted by Shire and Vifor Pharma; he has received royalties from CIP-Medien, Hogrefe, Kohlhammer, and Oxford University Press.
- Belsky J, Bakermans-Kranenburg M, van IJzendoorn MH: For better and for worse. Curr Dir Psychol Sci 2007; 16:300-304
- Mill J, Davies M, Volta M, et al: Methylomic profiling across brain and blood: Brain area-specific differentially methyl- ated regions, individual differences, and allele-specific DNA methylation, Presented at proceedings of the 12th Interna- tional Congress of Human Genetics/61st Annual Meeting of the American Society of Human Genetics, October 12, 2011, Montreal
Cited by
Sorted by citations
Biological embedding of experience: a primer on epigenetics
Aristizabal, M. J., Anreiter, I., Halldorsdottir, T., Odgers, C. L., McDade, T. W., Goldenberg, A., Mostafavi, S., Kobor, M. S., Binder, E. B., Sokolowski, M. B., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820838116 · Cited by 268 · see citing works
Schiele, M. A., Gottschalk, M. G., & Domschke, K. (2020) · Clinical Psychology Review · doi:10.1016/j.cpr.2020.101830 · Cited by 156 · see citing works
Genetics of substance use disorders in the era of big data
Gelernter, J. E., & Polimanti, R. A. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00377-1 · Cited by 102 · see citing works
Dugué, P., Wilson, R., Lehne, B., Jayasekara, H., Wang, X., Jung, C.-H., Joo, J., Makalic, E., Schmidt, D., Baglietto, L., et al. (2018) · bioRxiv · doi:10.1111/adb.12855 · Cited by 84 · see citing works
Cumulative Stressors and Adolescent Substance Use: A Review of 21st-Century Literature
Hoffmann, J. P., & Jones, M. S. (2020) · Trauma Violence & Abuse · doi:10.1177/1524838020979674 · Cited by 66 · see citing works
Garcia‐Ruiz, B., Moreno, L., Muntané, G., Sánchez‐Gistau, V., Gutiérrez‐Zotes, A., Martorell, L., Labad, J., & Vilella, E. (2020) · Epigenomics · doi:10.2217/epi-2019-0191 · Cited by 17 · see citing works
Zhang, Y., & Liu, C. (2022) · Epigenomics · doi:10.2217/epi-2021-0190 · Cited by 17 · see citing works
Tanabe, M., Kunisawa, K., Saito, I., Kosuge, A., Tezuka, H., Kawai, T., Kon, Y., Yoshidomi, K., Kagami, A., Hasegawa, M., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02826-9 · Cited by 9 · see citing works
Improving Our Understanding of Substance Use Disorders
Brady, K. T. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18121391 · Cited by 6 · see citing works
Psychiatrische Komorbidität bei Hidradenitis suppurativa/Acne inversa
Mavrogiorgou, P., Juckel, G., Reimelt, A., Hessam, S., Scholl, L., Frajkur, J. L., Stockfleth, E., & Bechara, F. G. (2021) · Der Hautarzt · doi:10.1007/s00105-020-04742-9 · Cited by 3 · see citing works
Cross‐Tissue Specificity of Pediatric DNA Methylation Associated With Cumulative Family Stress
Chan, M. H.-M., Merrill, S. M., Fatima, F., MacIsaac, J. L., Obradović, J., Boyce, W. T., & Kobor, M. S. (2025) · Developmental Psychobiology · doi:10.1002/dev.70097 · Cited by 1 · see citing works
Proposed effect of epigenetic alterations on stress-related disorders
Yılmaz, O. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-823039-8.00010-1
Cracking the Code of Neuronal Cell Fate
Morello, G., Cognata, V. L., Guarnaccia, M., D’Agata, V., & Cavallaro, S. (2023) · Cells · doi:10.3390/cells12071057
Feng, Y., & Shen, J. (2023) · Research Square · doi:10.21203/rs.3.rs-3402538/v1
Böhmer, J., Heinz, A., Schumann, G., & Walter, H. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_28
Self-citationAlmodóvar-Payá, C., Moreno, M., Guardiola-Ripoll, M., Latorre-Guardia, M., Morentín, B., Garcia‐Ruiz, B., Pomarol‐Clotet, E., Callado, L. F., Gallego, C., & Fatjó‐Vilas, M. (2024) · medRxiv · doi:10.1101/2024.10.29.24315982
SPDEF-mediated BIRC5 transcriptional activation enhances non-small cell lung cancer progression
Qiao, Z., Lv, Z., Song, X., & He, J. (2025) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2025.111926
Olaoye, O. J., Farrow, S. L., Cooper, A. A., Nyaga, D. M., & O'Sullivan, J. M. (2026) · BMC Medical Genomics · doi:10.1186/s12920-026-02375-w
- Authors
- Tay, N., Macare, C., Liu, Y., Ruggeri, B., Jia, T., Chu, C., Biondo, F., Ing, A., Luo, Q., Sarkysian, D., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Bromberg, U., Büchel, C., Quinlan, E. B., Desrivières, S., Flor, H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Martinot, J.-L., Artiges, E., Nees, F., Orfanos, D. P., Paus, T., Poustka, L., Hohmann, S., Fröhner, J. H., Smolka, M. N., Walter, H., Whelan, R., Frieling, H., Bleich, S., Barker, E. D., Syvänen, A.-C., Rüegg, J., Ekström, T. J., Bakalkin, G., Schumann, G., & the IMAGEN Consortium
- Affiliations
- King's College London (GB)
- The Centre for Population Neuroscience and Stratified Medicine and SGDP Centre, Institute of Psychiatry, King’s College London (Tay, Macare, Ruggeri, Jia, Chu, Biondo, Ing, Quinlan, Desrivières, Barker, Schumann); the Department of Biochemistry and Molecular Biology, MOE Key Laboratory of Metabolism and Molecular Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, China (Liu); the Institute of Science and Technology of Brain-Inspired Intelligence, Fudan University, Shanghai, China ...
- ORCID
- Tay, Nicole
- Liu, Yun
- Ruggeri, Barbara
- Jia, Tianye
- Chu, Congying
- Biondo, Francesca
- Ing, Alex
- Luo, Qiang
- Banaschewski, Tobias
- Barker, Gareth J.
- Bokde, Arun L.W.
- Bromberg, Uli
- Büchel, Christian
- Quinlan, Erin Burke
- Desrivières, Sylvane
- Flor, Herta
- Frouin, Vincent
- Garavan, Hugh
- Gowland, Penny
- Heinz, Andreas
- Ittermann, Bernd
- Martinot, Jean-Luc
- Nees, Frauke
- Orfanos, Dimitri Papadopoulos
- Paus, Tomáš
- Poustka, Luise
- Hohmann, Sarah
- Fröhner, Juliane H.
- Smolka, Michael N.
- Walter, Henrik
- Whelan, Robert
- Frieling, Helge
- Bleich, Stefan
- Barker, Edward D.
- Rüegg, Joëlle
- Ekström, Tomas J.
- Bakalkin, Georgy
- Venue
- American Journal of Psychiatry
- Published
- 2019-02-01
- Volume
- 176
- Issue
- 2
- Pages
- 146-155
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2905516213
- Cited by
- 18
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Eli Lilly and Company
- Fondation de l'Avenir pour la Recherche Médicale Appliquée
- University of Oxford
- Science Foundation Ireland (16/ERCD/3797, RO1 MH085772-01A1)
- Deutsche Forschungsgemeinschaft (SFB) 940/1, FOR1617, SM 80/7–2, 1, SM 80/7, SM 80/7-1, SFB940)
- Agence Nationale de la Recherche (AF12-NEUR0008–01 - WM2NA, AF12-NEUR0008-01, ANR-12-SAMA-0004, WM2NA, ANR-12)
- Fondation pour la Recherche Médicale (DPA20140629802)
- Fondation de France
- Vifor Pharma
- Mission Interministérielle de Lutte Contre les Drogues et les Conduites Addictives
- Servier
- H. Lundbeck A/S
- National Institutes of Health (16/ERCD/3797, EB020403)
- Medical Research Council (MR/N000390/1)
- National Institute of Mental Health (R01MH085772)
- National Institute of Biomedical Imaging and Bioengineering (U54EB020403)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- SPDEF, DNA methylation, psychosocial stress, adolescent substance abuse, alcohol consumption, tobacco use, allele-specific methylation, differentially methylated regions, life events, gray matter volume, cuneus
- MeSH terms
- Underage Drinking, Adolescent, Alcohol Drinking, Alleles, Female, Humans, Male, Occipital Lobe, Organ Size, Stress, Psychological, DNA Methylation, Substance-Related Disorders, Epigenesis, Genetic, Proto-Oncogene Proteins c-ets, Tobacco Use, Gray Matter
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
