No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples
Open accessAbstract
OBJECTIVE: Interest in candidate gene and candidate gene-by-environment interaction hypotheses regarding major depressive disorder remains strong despite controversy surrounding the validity of previous findings. In response to this controversy, the present investigation empirically identified 18 candidate genes for depression that have been studied 10 or more times and examined evidence for their relevance to depression phenotypes. METHODS: Utilizing data from large population-based and case-control samples (Ns ranging from 62,138 to 443,264 across subsamples), the authors conducted a series of preregistered analyses examining candidate gene polymorphism main effects, polymorphism-by-environment interactions, and gene-level effects across a number of operational definitions of depression (e.g., lifetime diagnosis, current severity, episode recurrence) and environmental moderators (e.g., sexual or physical abuse during childhood, socioeconomic adversity). RESULTS: No clear evidence was found for any candidate gene polymorphism associations with depression phenotypes or any polymorphism-by-environment moderator effects. As a set, depression candidate genes were no more associated with depression phenotypes than noncandidate genes. The authors demonstrate that phenotypic measurement error is unlikely to account for these null findings. CONCLUSIONS: The study results do not support previous depression candidate gene findings, in which large genetic effects are frequently reported in samples orders of magnitude smaller than those examined here. Instead, the results suggest that early hypotheses about depression candidate genes were incorrect and that the large number of associations reported in the depression candidate gene literature are likely to be false positives.
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?
Erroneous results from SNP-chips used in research biobanks can lead to false associations and wasted resource in the development of new treatments against the wrong targets.
“However, erroneous results from SNP-chips used in research biobanks can also lead to false associations [32] and wasted resource in the development of new treatments against the wrong targets [33].”
From Assessing the analytical validity of SNP-chips for detecting very rare pathogenic variants: implications for direct-to-consumer genetic testing (2019) · cites this paper as [33]
The Conclusions discuss a potentially high false-discovery rate among published candidate-gene associations, so the paper supports the possibility of false associations. It does not attribute those associations to erroneous SNP-chip results in research biobanks; it discusses small samples, analytic methods and publication bias instead. The treatment-development claim has a separate citation [33] and is not attributed to this source. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe trade-off between phenotype depth and sample size may be effective for gene discovery.
“Though resulting measures are typically crude compared to the measures included in smaller studies [240], the trade-off between phenotype depth and sample size may be effective for gene discovery [241], as demonstrated by a recent preliminary report [242] of a GWAS for the Common CC factor.”
From The role of prefrontal cortex in cognitive control and executive function (2022) · cites this paper as [241]
The “Sensitivity of Results to Measurement Error” section (pp. 381–383) reports simulations in which a large sample retained approximately 100% power to detect specified candidate-gene effects despite severe measurement error. This supports the possibility that sample size can offset less precise phenotyping, but the paper does not show that this trade-off produced gene discoveries; its candidate-gene results were largely null. (LLM, conf=0.80)
Experimental — accuracy not yet measuredErroneous results from SNP chips used in research biobanks can lead to false associations and wasted resource in the development of new treatments against the wrong targets.
“However, erroneous results from SNP chips used in research biobanks can also lead to false associations and wasted resource in the development of new treatments against the wrong targets.33 34 35”
From Use of SNP chips to detect rare pathogenic variants: retrospective, population based diagnostic evaluation (2021) · cites this paper as [35]
The Discussion (p. 385) concludes that earlier positive associations between candidate genes and depression were false positives. It does not attribute those false associations to erroneous SNP-chip results in biobanks or discuss wasted resources developing treatments against wrong targets. (LLM, conf=0.84)
Experimental — accuracy not yet measuredOne study indicated no support for depression candidate gene findings.
“One study indicated no support for depression candidate gene findings [122].”
From Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature (2021) · cites this paper as [122]
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
The PHQ-9: Validity of a brief depression severity measure
Kroenke, K., Spitzer, R. L., & Williams, J. B. W. (2001) · Journal of General Internal Medicine · doi:10.1046/j.1525-1497.2001.016009606.x · Cited by 44,910 · see citing works
Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728 · see citing works
Spitzer, R. L. (1999) · JAMA · doi:10.1001/jama.282.18.1737 · Cited by 9,802 · see citing works
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · 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
Biopython: freely available python tools for computational molecular biology and bioinformatics
Cock, P. J. A., Antao, T., Chang, J. T., Chapman, B. A., Cox, C. J., Dalke, A., Friedberg, I., Hamelryck, T., Kauff, F., Wilczynski, B., et al. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp163 · Cited by 6,080 · see citing works
Role of genotype in the cycle of violence in maltreated children
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., Taylor, A., & Poulton, R. (2002) · Science · doi:10.1126/science.1072290 · Cited by 4,842 · see citing works
An atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255 · 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
Genetic Epidemiology of Major Depression: Review and Meta-Analysis
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.10.1552 · Cited by 3,431 · see citing works
Self-citationGenetic Dissection of Complex Traits
Lander, E. S., & Schork, N. J. (1994) · Science · doi:10.1126/science.8091226 · Cited by 3,425 · 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
Allelic Variation of Human Serotonin Transporter Gene Expression
Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., & Lesch, K. P. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66062621.x · Cited by 2,221 · see citing works
Reference-based phasing using the Haplotype Reference Consortium panel
Loh, P.-R., Danecek, P., Palamara, P. F., Fuchsberger, C., A Reshef, Y., K Finucane, H., Schoenherr, S., Forer, L., McCarthy, S., Abecasis, G. R., et al. (2016) · Nature Genetics · doi:10.1038/ng.3679 · Cited by 1,894 · see citing works
Increasing Transparency Through a Multiverse Analysis
Steegen, S., Tuerlinckx, F., Gelman, A., & Vanpaemel, W. (2016) · Perspectives on Psychological Science · doi:10.1177/1745691616658637 · Cited by 1,388 · see citing works
Problems of reporting genetic associations with complex outcomes
Colhoun, H. M., McKeigue, P., & Smith, G. D. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12715-8 · Cited by 1,203 · see citing works
Gene-environment interplay and psychopathology: multiple varieties but real effects
Rutter, M., Moffitt, T. E., & Caspi, A. (2006) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2005.01557.x · Cited by 1,058 · see citing works
Duncan, L. E., & Keller, M. C. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020191 · Cited by 1,032 · see citing works
Self-citationGenetic Heterogeneity in Human Disease
McClellan, J., & King, M.-C. (2010) · Cell · doi:10.1016/j.cell.2010.03.032 · Cited by 981 · see citing works
Kapur, S., Phillips, A. G., & Insel, T. R. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.105 · Cited by 980 · see citing works
Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter
Owens, M. J., & Nemeroff, C. B. (1994) · Clinical Chemistry · doi:10.1093/clinchem/40.2.288 · Cited by 934 · see citing works
Ramamoorthy, S., Bauman, A. L., Moore, K. R., Han, H. J., Yang‐Feng, T. L., Chang, A. S., Ganapathy, V., & Blakely, R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2542 · Cited by 880 · see citing works
The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
the Alzheimer’s Disease Neuroimaging Initiative, E. C., Thompson, P. M., Stein, J. L., Medland, S. E., Hibar, D. P., Vasquez, A. A., Renteria, M. E., Toro, R., Jahanshad, N., Schumann, G., et al. (2014) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9269-5 · Cited by 838 · see citing works
Collider scope: when selection bias can substantially influence observed associations
Munafò, M. R., Tilling, K., Taylor, A. E., Evans, D. M., & Davey Smith, G. (2018) · International Journal of Epidemiology · doi:10.1093/ije/dyx206 · Cited by 813 · see citing works
Health and deprivation. Inequality and the North
Mackenbach, J. P. (1988) · Health Policy · doi:10.1016/0168-8510(88)90006-1 · Cited by 672 · see citing works
Keller, M. C. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.006 · Cited by 627 · see citing works
Self-citationWendland, J. R., Martin, B. J., Kruse, M. R., Lesch, K., & Murphy, D. L. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001789 · Cited by 561 · see citing works
Linkage disequilibrium mapping of complex disease: fantasy or reality?
Terwilliger, J., & Weiss, K. (1998) · Current Opinion in Biotechnology · doi:10.1016/s0958-1669(98)80135-3 · Cited by 382 · see citing works
Smıth, D. J., Nicholl, B. I., Cullen, B., Martin, D. J., Haq, Z. U., Evans, J. J., Gill, J. M. R., Roberts, B. A., Gallacher, J., Mackay, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075362 · Cited by 361 · see citing works
Candidate Gene–Environment Interaction Research
Dick, D. M., Arpana Agrawal, A., Keller, M. C., Adkins, A. E., Alıev, F., Monroe, S. M., Hewitt, J. K., Kendler, K. S., & Sher, K. J. (2015) · Perspectives on Psychological Science · doi:10.1177/1745691614556682 · Cited by 358 · see citing works
Self-citationAdjusting researchers’ approach to adjustment: On the use of covariates when testing interactions
Yzerbyt, V. Y., Müller, D., & Judd, C. M. (2003) · Journal of Experimental Social Psychology · doi:10.1016/j.jesp.2003.10.001 · Cited by 332 · see citing works
Culverhouse, R., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., Burmeister, M., Cohen‐Woods, S., Étain, B., Fisher, H. L., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.44 · Cited by 321 · see citing works
Self-citationEvaluating historical candidate genes for schizophrenia
Farrell, M. S., Werge, T., Sklar, P., Owen, M. J., Ophoff, R. A., O'Donovan, M. C., Corvin, A., Cichon, S., & Sullivan, P. F. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.16 · Cited by 315 · see citing works
Self-citationPoor replication of candidate genes for major depressive disorder using genome-wide association data
Bosker, F. J., Hartman, C. A., Nolte, I. M., Prins, B. P., Terpstra, P., Posthuma, D., van Veen, T., Willemsen, G., DeRijk, R. H., de Geus, E. J., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.38 · Cited by 309 · see citing works
Self-citationGene-environment interaction and psychiatric disorders: Review and future directions
Assary, E., Vincent, J. P., Keers, R., & Pluess, M. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.10.016 · Cited by 275 · see citing works
Burton, P. R., Hansell, A., Fortier, I., Manolio, T. A., Khoury, M. J., Little, J., & Elliott, P. (2008) · International Journal of Epidemiology · doi:10.1093/ije/dyn147 · Cited by 258 · see citing works
Gene–Environment Interactions in Severe Mental Illness
Uher, R. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00048 · Cited by 251 · see citing works
Johnson, E. C., Border, R., Melroy-Greif, W. E., de Leeuw, C., Ehringer, M. A., & Keller, M. C. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.06.033 · Cited by 201 · see citing works
Self-citationUher, R., Caspi, A., Houts, R., Sugden, K., Williams, B. S., Poulton, R., & Moffitt, T. E. (2011) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.03.010 · Cited by 154 · see citing works
Recent progress in psychiatric genetics--some hope but no hype
Stoltenberg, S. F. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.6.927 · Cited by 103 · see citing works
Stallings, M. C., Corley, R. P., Hewitt, J. K., Krauter, K. S., Lessem, J. M., Mikulich, S. K., Rhee, S. H., Smolen, A., Young, S. E., & Crowley, T. J. (2003) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(03)00031-0 · Cited by 96 · see citing works
Self-citationIntergenerational Continuity and Discontinuity in Harsh Parenting
Conger, R., Schofield, T., & Neppl, T. (2012) · Parenting, science and practice · doi:10.1080/15295192.2012.683360 · Cited by 80 · see citing works
Genome‐wide gene‐environment interaction in depression: A systematic evaluation of candidate genes
der Auwera, S. V., Peyrot, W. J., Milaneschi, Y., Hertel, J., Baune, B. T., Breen, G. D., Byrne, E. M., Dunn, E. C., Fisher, H. L., Homuth, G., et al. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32593 · Cited by 69 · see citing works
Self-citationGenetic association studies of alcoholism -- problems with the candidate gene approach
Buckland, P. R. (2001) · Alcohol and Alcoholism · doi:10.1093/alcalc/36.2.99 · Cited by 61 · see citing works
Genome-wide association study of behavioral disinhibition in a selected adolescent sample
Derringer, J., Corley, R., Haberstick, B. C., Young, S., Demmitt, B. A., Howrigan, D., Kirkpatrick, R. M., Iacono, W., McGue, M., Keller, M. C., et al. (2015) · Behavior Genetics · doi:10.1007/s10519-015-9705-y · Cited by 60 · see citing works
Self-citationCandidate gene studies in the 21st century: meta‐analysis, mediation, moderation
Munafo, M. R. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00188.x · Cited by 55 · see citing works
Munafo, M. R., Zammit, S., & Jonathan Flint, C. (2014) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12261 · Cited by 51 · see citing works
The VNTR in complex disorders: The forgotten polymorphisms? A functional way forward?
Brookes, K. J. (2013) · Genomics · doi:10.1016/j.ygeno.2013.03.003 · Cited by 47 · see citing works
Moore, S. R. (2017) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12697 · Cited by 44 · see citing works
Reliability and replicability of genetic association studies
Munafo, M. R. (2009) · Addiction · doi:10.1111/j.1360-0443.2009.02662.x · Cited by 43 · see citing works
Border, R., & Keller, M. C. (2017) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12669 · Cited by 34 · see citing works
Self-citationMapping genes for psychiatric disorders and behavioral traits
McInnes, L. A., Reus, V. I., & Freimer, N. B. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80083-x · Cited by 25 · see citing works
Improving the reliability and reporting of genetic association studies
Munafo, M. R., & Gage, S. H. (2013) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2013.03.023 · Cited by 21 · see citing works
Jahanshad, N., Ganjgahi, H., Bralten, J., den Braber, A., Faskowitz, J., Knodt, A. R., Lemaître, H., Nir, T. M., Patel, B., Richie, S., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/107987 · Cited by 19 · see citing works
Border, R., Smolen, A., Corley, R. P., Stallings, M. C., Brown, S. A., Conger, R. D., Derringer, J. L., Donnellan, M. B., Haberstick, B. C., Hewitt, J. K., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0349-x · Cited by 18 · see citing works
Self-citationColeman, J. R. I., Purves, K. L., Davis, K. A. S., Rayner, C., Choi, S. W., Hübel, C., Gaspar, H. A., Kan, C., der Auwera, S. V., Adams, M. J., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/247353 · Cited by 18 · see citing works
Gonda, X., Eszlári, N., Kovács, D., Anderson, I. M., Deakin, J. F. W., Juhász, G., & Bagdy, G. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.57 · Cited by 17 · see citing works
Mapping genes for psychiatric disorders and behavioral traits
McInnes, L. A., & Freimer, N. B. (1995) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(95)80054-9 · Cited by 16 · see citing works
DISCovery in psychiatric genetics
Niculescu, A. B. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.176 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [35]35. Munafò MR, Zammit S, Flint J: Limitations of gene 3 environment interaction models in psychiatry. J Child Psychol Psychiatry 2014; 55:1092-1101
- [57]57. Miller S, Wain L, Shrine N, et al: The UK BiLEVE study: the first genetic study in UK Biobank identifies novel regions associated with airway obstruction and smoking behaviour. Presented at the American Thoracic Society 2015 International Conference. Avail- able in American Thoracic Society International Conference Abstracts, B31 Inflammation and COPD, 2015, p A2714. https:// www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2015.191.1_ MeetingAbstracts.A2714 · DOI
Cited by
Sorted by citations
The Bidirectional Relationship of Depression and Inflammation: Double Trouble
Beurel, E., Toups, M., & Nemeroff, C. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.002 · Cited by 2,136 · see citing works
Reproducible brain-wide association studies require thousands of individuals
Marek, S. A., Tervo‐Clemmens, B., Calabro, F. J., Montez, D. F., Kay, B. P., Hatoum, A. S., Donohue, M. R., Foran, W., Miller, R. L., Hendrickson, T. J., et al. (2022) · Nature · doi:10.1038/s41586-022-04492-9 · Cited by 1,949 · see citing works
The role of prefrontal cortex in cognitive control and executive function
Friedman, N. P., & Robbins, T. W. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01132-0 · Cited by 1,737 · see citing works
“Though resulting measures are typically crude compared to the measures included in smaller studies [240], the trade-off between phenotype depth and sample size may be effective for gene discovery [241], as demonstrated by a recent preliminary report [242] of a GWAS for the Common CC factor.”
BackgroundThe serotonin theory of depression: a systematic umbrella review of the evidence
Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01661-0 · Cited by 960 · see citing works
Thompson, P. M., Jahanshad, N., Ching, C. R. K., Salminen, L. E., Thomopoulos, S. I., Bright, J. K., Baune, B. T., Bertolín, S., Bralten, J., Bruin, W. B., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0705-1 · Cited by 638 · see citing works
Malhi, G. S., Bell, E., Bassett, D., Boyce, P., Bryant, R., Hazell, P., Hopwood, M., Lyndon, B., Mulder, R., Porter, R., et al. (2021) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867420979353 · Cited by 614 · see citing works
Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders
Sullivan, P. F., & Geschwind, D. H. (2019) · Cell · doi:10.1016/j.cell.2019.01.015 · Cited by 452 · see citing works
Self-citationBiological, Psychological, and Social Determinants of Depression: A Review of Recent Literature
Remes, O., Mendes, J. F., & Templeton, P. (2021) · Brain Sciences · doi:10.3390/brainsci11121633 · Cited by 482 · see citing works
Depression Heterogeneity and Its Biological Underpinnings: Toward Immunometabolic Depression
Milaneschi, Y., Lamers, F., Berk, M., & Penninx, B. W. J. H. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.01.014 · Cited by 433 · see citing works
Gender Differences in Depression: Biological, Affective, Cognitive, and Sociocultural Factors
Hyde, J. S., & Mezulis, A. H. (2020) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000230 · Cited by 385 · see citing works
Nosek, B. A., & Errington, T. M. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000691 · Cited by 401 · see citing works
Hare, B. D., & Duman, R. S. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0685-9 · Cited by 366 · see citing works
On the limits of fitting complex models of population history to f-statistics
Maier, R., Flegontov, P., Flegontova, O., Işıldak, U., Changmai, P., & Reich, D. (2023) · eLife · doi:10.7554/elife.85492 · Cited by 274 · see citing works
Dissecting diagnostic heterogeneity in depression by integrating neuroimaging and genetics
Buch, A. M., & Liston, C. M. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00789-3 · Cited by 271 · see citing works
Hayes, S. C., & Hofmann, S. G. (2021) · World Psychiatry · doi:10.1002/wps.20884 · Cited by 260 · see citing works
Quintana, D. S., Lischke, A., Grace, S., Scheele, D., Ma, Y., & Becker, B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00864-7 · Cited by 263 · see citing works
Andreassen, O. A., Hindley, G., Frei, O., & Smeland, O. B. (2023) · World Psychiatry · doi:10.1002/wps.21034 · Cited by 255 · see citing works
Central 5-HT receptors and their function; present and future
Sharp, T., & Barnes, N. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108155 · Cited by 227 · see citing works
How genome-wide association studies (GWAS) made traditional candidate gene studies obsolete
Duncan, L. E., Ostacher, M. J., & Ballon, J. S. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0389-5 · Cited by 230 · see citing works
The genetic basis of major depression
Kendall, K. M., Van Assche, E., Andlauer, T. F. M., Choi, K. W., Luykx, J. J., Schulte, E. C., & Lu, Y. (2021) · Psychological Medicine · doi:10.1017/s0033291721000441 · Cited by 213 · see citing works
Towards Reproducible Brain-Wide Association StudiesPreprint
Marek, S. A., Tervo‐Clemmens, B., Calabro, F. J., Montez, D. F., Kay, B. P., Hatoum, A. S., Donohue, M. R., Foran, W., Miller, R. L., Feczko, E., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.21.257758 · Cited by 185 · see citing works
Protecting against researcher bias in secondary data analysis: challenges and potential solutions
Baldwin, J. R., Pingault, J.-B., Schoeler, T., Sallis, H. M., & Munafò, M. R. (2022) · European Journal of Epidemiology · doi:10.1007/s10654-021-00839-0 · Cited by 178 · see citing works
The Past, Present, and Future of Ego Depletion
Inzlicht, M., & Friese, M. (2019) · Social Psychology · doi:10.1027/1864-9335/a000398 · Cited by 180 · see citing works
Childhood maltreatment and DNA methylation: A systematic review
Cecil, C. A. M., Zhang, Y., & Nolte, T. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.02.019 · Cited by 171 · see citing works
Genetics of restless legs syndrome
Winkelmann, J., Schormair, B., Xiong, L., Dion, P. A., Rye, D. B., & Rouleau, G. A. (2002) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-008-0033-y · Cited by 173 · see citing works
Mechanisms of ketamine and its metabolites as antidepressants
Hess, E. M., Riggs, L. M., Michaelides, M., & Gould, T. D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114892 · Cited by 169 · see citing works
Uncovering the Genetic Architecture of Major Depression
McIntosh, A. M., Sullivan, P. F., & Lewis, C. M. (2019) · Neuron · doi:10.1016/j.neuron.2019.03.022 · Cited by 160 · see citing works
Self-citationThe complex neurobiology of resilient functioning after childhood maltreatment
Ioannidis, K., Askelund, A. D., Kievit, R., & van Harmelen, A. (2020) · BMC Medicine · doi:10.1186/s12916-020-1490-7 · Cited by 163 · see citing works
The genetic basis of major depressive disorder
Jonathan Flint, C. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01957-9 · Cited by 141 · see citing works
Resilience and Disaster: Flexible Adaptation in the Face of Uncertain Threat
Bonanno, G. A., Chen, S., Bagrodia, R., & Galatzer‐Levy, I. R. (2023) · Annual Review of Psychology · doi:10.1146/annurev-psych-011123-024224 · Cited by 153 · see citing works
Anxiety, Depression, and Suicide in Youth
Kalin, N. H. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.21020186 · Cited by 131 · see citing works
Lüscher, B., & Möhler, H. (2019) · F1000Research · doi:10.12688/f1000research.18758.1 · Cited by 105 · see citing works
“Reports of My Death Were Greatly Exaggerated”: Behavior Genetics in the Postgenomic Era
Harden, K. P. (2020) · Annual Review of Psychology · doi:10.1146/annurev-psych-052220-103822 · Cited by 120 · see citing works
Schweizer-Schubert, S., Gordon, J. L., Eisenlohr-Moul, T. A., Meltzer-Brody, S. E., Schmalenberger, K. M., Słopień, R., Zietlow, A., Ehlert, U., & Ditzen, B. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2020.479646 · Cited by 118 · see citing works
Genome-wide association study of musical beat synchronization demonstrates high polygenicity
Niarchou, M., Gustavson, D. E., Sathirapongsasuti, J. F., Anglada-Tort, M., Eising, E., Bell, E., McArthur, E., Straub, P., Aslibekyan, S. W., Auton, A., et al. (2022) · Nature Human Behaviour · doi:10.1038/s41562-022-01359-x · Cited by 113 · see citing works
Sperm microRNAs confer depression susceptibility to offspring
Wang, Y., Chen, Z., Hu, H., Lei, J., Zhou, Z., Yao, B., Chen, L., Liang, G., Zhan, S., Zhu, X., et al. (2021) · Science Advances · doi:10.1126/sciadv.abd7605 · Cited by 108 · 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
(2022) · doi:10.1016/j.biopsych.2022.06.034 · Cited by 115 · see citing works
Self-citationDissecting polygenic signals from genome-wide association studies on human behaviour
Abdellaoui, A., & Verweij, K. J. H. (2021) · Nature Human Behaviour · doi:10.1038/s41562-021-01110-y · Cited by 95 · see citing works
Pathways to well-being: Untangling the causal relationships among biopsychosocial variables
Karunamuni, N. D., Imayama, I., & Goonetilleke, D. (2020) · Social Science & Medicine · doi:10.1016/j.socscimed.2020.112846 · Cited by 102 · see citing works
Sariola, S., & Gilbert, S. F. (2020) · Microorganisms · doi:10.3390/microorganisms8050746 · Cited by 97 · see citing works
The Burden of Antipsychotic-Induced Weight Gain and Metabolic Syndrome in Children
Libowitz, M. R., & Nurmi, E. L. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.623681 · Cited by 99 · see citing works
Elbau, I., Cruceanu, C., & Binder, E. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.04.025 · Cited by 91 · see citing works
Davies, M. R., Kalsi, G., Armour, C., Jones, I. R., McIntosh, A. M., Smıth, D. J., Walters, J., Bradley, J. R., Kingston, N., Ashford, S. E., et al. (2019) · Behaviour Research and Therapy · doi:10.1016/j.brat.2019.103503 · Cited by 91 · see citing works
Twin studies to GWAS: there and back again
Friedman, N. P., Banich, M. T., & Keller, M. C. (2021) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2021.06.007 · Cited by 83 · see citing works
Self-citationDNA methylation and brain structure and function across the life course: A systematic review
Wheater, E., Stoye, D. Q., Cox, S. R., Wardlaw, J. M., Drake, A. J., Bastin, M. E., & Boardman, J. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.03.007 · Cited by 82 · see citing works
de Vries, L. P., van de Weijer, M. P., & Bartels, M. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104733 · Cited by 81 · see citing works
American psychiatry in the new millennium: a critical appraisal
Scull, A. T. (2021) · Psychological Medicine · doi:10.1017/s0033291721001975 · Cited by 77 · see citing works
Robinson, M. C., Glen, R. C., & Lee, A. A. (2020) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-019-00274-0 · Cited by 75 · see citing works
Illusory Essences: A Bias Holding Back Theorizing in Psychological Science
Brick, C., Hood, B. M., Ekroll, V., & de‐Wit, L. (2021) · Perspectives on Psychological Science · doi:10.1177/1745691621991838 · Cited by 72 · see citing works
Early Life Stress, Physiology, and Genetics: A Review
Fogelman, N., & Canli, T. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.01668 · Cited by 72 · see citing works
Syme, K., & Hagen, E. H. (2019) · American Journal of Physical Anthropology · doi:10.1002/ajpa.23965 · Cited by 75 · see citing works
Boba: Authoring and Visualizing Multiverse Analyses
Liu, Y., Kale, A. M., Althoff, T., & Heer, J. (2020) · IEEE Transactions on Visualization and Computer Graphics · doi:10.1109/tvcg.2020.3028985 · Cited by 73 · see citing works
A review of Mendelian randomization in amyotrophic lateral sclerosis
Julian, T. H., Boddy, S. L., Islam, M., Kurz, J. M., Whittaker, K. J., Moll, T., Harvey, C., Zhang, S., Snyder, M. P., McDermott, C. J., et al. (2021) · Brain · doi:10.1093/brain/awab420 · Cited by 68 · see citing works
Replicable brain–phenotype associations require large-scale neuroimaging data
Liu, S., Abdellaoui, A., Verweij, K. J. H., & van Wingen, G. A. (2023) · Nature Human Behaviour · doi:10.1038/s41562-023-01642-5 · Cited by 64 · see citing works
Putting Psychology to the Test: Rethinking Model Evaluation Through Benchmarking and Prediction
Rocca, R., & Yarkoni, T. (2021) · Advances in Methods and Practices in Psychological Science · doi:10.1177/25152459211026864 · Cited by 59 · see citing works
Mindsets in the clinic: Applying mindset theory to clinical psychology
Schroder, H. S. (2020) · Clinical Psychology Review · doi:10.1016/j.cpr.2020.101957 · Cited by 63 · see citing works
Precision psychiatry in clinical practice
Zanardi, R., Prestifilippo, D., Fabbri, C., Colombo, C., Maron, E., & Serretti, A. (2020) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2020.1809680 · Cited by 57 · see citing works
MN, W., L, J., JW, H., KS, R., J, T., AT, H., & CF, W. (2021) · BMJ · doi:10.1136/bmj.n214 · Cited by 51 · see citing works
The role of serotonin in depression—A historical roundup and future directions
Bremshey, S., Groß, J., Renken, K., & Masseck, O. A. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16097 · Cited by 60 · see citing works
Montag, C., Ebstein, R. P., Jawinski, P., & Markett, S. A. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.06.020 · Cited by 55 · see citing works
Wendt, F. R., Pathak, G. A., Levey, D. F., Nuñez, Y. Z., Overstreet, C. M., Tyrrell, C., Adhikari, K., Angelis, F. D., Tylee, D. S., Goswami, A., et al. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100309 · Cited by 55 · see citing works
Genetic Architecture and Molecular Neuropathology of Human Cocaine Addiction
Huggett, S. B., & Stallings, M. C. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2879-19.2020 · Cited by 47 · see citing works
Multivariable G-E interplay in the prediction of educational achievement
Allegrini, A. G., Karhunen, V., Coleman, J. R. I., Selzam, S., Rimfeld, K., von Stumm, S., Pingault, J., & Plomin, R. J. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1009153 · Cited by 48 · see citing works
The Role of Eating Behaviours in Genetic Susceptibility to Obesity
Herle, M., Smith, A. D., Kininmonth, A. R., & Llewellyn, C. H. (2020) · Current Obesity Reports · doi:10.1007/s13679-020-00402-0 · Cited by 53 · see citing works
Biological correlates of early life stressful events in major depressive disorder
Silva, R. C., Maffioletti, E., Gennarelli, M., Baune, B. T., & Minelli, A. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.105103 · Cited by 53 · see citing works
Inflamed brain: Targeting immune changes and inflammation for treatment of depression
Sakamoto, S., Zhu, X., Hasegawa, Y., Karma, S., Obayashi, M., Alway, E., & Kamiya, A. (2021) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13286 · Cited by 51 · see citing works
The Genetically Informed Neurobiology of Addiction (GINA) model
Bogdan, R., Hatoum, A. S., Johnson, E. C., & Arpana Agrawal, A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00656-8 · Cited by 54 · see citing works
Self-citationSchroder, H. S., Duda, J. M., Christensen, K., Beard, C., & Björgvinsson, Þ. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.07.061 · Cited by 54 · see citing works
Psychiatric Genetics Begins to Find Its Footing
Smoller, J. W. (2019) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19060643 · Cited by 49 · see citing works
Molecular genetic overlap between posttraumatic stress disorder and sleep phenotypes
Lind, M. J., Brick, L. A. D., Gehrman, P., Duncan, L. E., Gelaye, B., Maihofer, A. X., Nievergelt, C. M., Nugent, N. R., Stein, M. B., Amstadter, A. B., et al. (2019) · SLEEP · doi:10.1093/sleep/zsz257 · Cited by 48 · see citing works
Self-citationBiomarkers of suicidal behaviors: A comprehensive critical review
Capuzzi, E., Caldiroli, A., Capellazzi, M., Tagliabue, I., Buoli, M., & Clerici, M. (2019) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.11.005 · Cited by 48 · see citing works
The interaction of biopsychological and socio-environmental influences on criminological outcomes
Barnes, J. C., Raine, A., & Farrington, D. P. (2020) · Justice Quarterly · doi:10.1080/07418825.2020.1730425 · Cited by 47 · see citing works
Barriers to Implementing Clinical Pharmacogenetics Testing in Sub-Saharan Africa. A Critical Review
Tata, E. B., Ambele, M. A., & Pepper, M. S. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12090809 · Cited by 47 · see citing works
Applying an evolutionary mismatch framework to understand disease susceptibility
Lea, A. J., Clark, A. G., Dahl, A., Devinsky, O., García, A. R., Golden, C. D. W., Kamau, J., Kraft, T. S., Lim, Y. A. L., Martins, D. J., et al. (2023) · PLoS Biology · doi:10.1371/journal.pbio.3002311 · Cited by 54 · see citing works
Genome-wide association study and polygenic risk score analysis of esketamine treatment response
Li, Q. S., Wajs, E., Ochs-Ross, R., Singh, J. B., & Drevets, W. C. (2020) · Scientific Reports · doi:10.1038/s41598-020-69291-6 · Cited by 47 · see citing works
Fried, E. I., Rieble, C., & Rieble, C. (2023) · Clinical Psychology in Europe · doi:10.32872/cpe.10075 · Cited by 52 · see citing works
Polygenic Scores in Developmental Psychology: Invite Genetics In, Leave Biodeterminism Behind
Raffington, L., Mallard, T. T., & Harden, K. P. (2020) · Annual Review of Developmental Psychology · doi:10.1146/annurev-devpsych-051820-123945 · Cited by 42 · see citing works
Liu, Y., Althoff, T., & Heer, J. (2020) · CHI Conference on Human Factors in Computing Systems · doi:10.1145/3313831.3376533 · Cited by 44 · see citing works
Social Factors in the Personality Disorders
Paris, J. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108867542 · Cited by 43 · see citing works
The Genetics of Externalizing Problems
Barr, P. B., & Dick, D. M. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2019_120 · Cited by 41 · see citing works
Wand, T., Glover, S., & Paul, D. (2021) · International Journal of Mental Health Nursing · doi:10.1111/inm.12947 · Cited by 46 · see citing works
Mineka, S., Williams, A. L., Wolitzky-Taylor, K. B., Vrshek‐Schallhorn, S., Craske, M. G., Hammen, C. L., & Zinbarg, R. E. (2020) · Journal of Abnormal Psychology · doi:10.1037/abn0000530 · Cited by 42 · see citing works
Milosavljević, F., Molden, E., Ingelman‐Sundberg, M., & Jukić, M. M. (2024) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2024.01.005 · Cited by 41 · see citing works
Willoughby, E. A., Polderman, T. J. C., & Boutwell, B. B. (2023) · Nature Reviews Methods Primers · doi:10.1038/s43586-022-00191-x · Cited by 40 · see citing works
Genetic Variants Associated With Resilience in Human and Animal Studies
Cahill, S., Chandola, T., & Hager, R. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.840120 · Cited by 43 · see citing works
Examining the shared etiology of psychopathology with genome-wide association studies
Mallard, T. T., Grotzinger, A. D., & Smoller, J. W. (2023) · Physiological Reviews · doi:10.1152/physrev.00016.2022 · Cited by 38 · see citing works
Toward Open and Reproducible Epidemiology
Mathur, M. B., & Fox, M. P. (2023) · American Journal of Epidemiology · doi:10.1093/aje/kwad007 · Cited by 46 · see citing works
Baverstock, K. F. (2021) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2021.04.005 · Cited by 38 · see citing works
Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders
Göver, T., & Ślęzak, M. (2024) · Pharmacological Reports · doi:10.1007/s43440-024-00654-w · Cited by 40 · see citing works
D’Souza, T., & Rajkumar, A. P. (2019) · Acta Neuropsychiatrica · doi:10.1017/neu.2019.28 · Cited by 37 · see citing works
Kelly, C. A., Freeman, K. B., & Schumacher, J. A. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104578 · Cited by 37 · see citing works
Treble‐Barna, A., Heinsberg, L. W., Stec, Z., Breazeale, S., Davis, T. S., Kesbhat, A., Chattopadhyay, A., VonVille, H. M., Ketchum, A., Yeates, K. O., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105078 · Cited by 37 · see citing works
Tomasi, J., Lisoway, A. J., Zai, C. C. H., Harripaul, R., Müller, D. J., Zai, G. C., McCabe, R. E., Richter, M. A., Kennedy, J. L., & Tiwari, A. K. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.09.002 · Cited by 36 · see citing works
Newbury, D. F., Gibson, J. L., Conti‐Ramsden, G., Pickles, A. R., Durkin, K., & Toseeb, U. (2019) · Journal of Speech Language and Hearing Research · doi:10.1044/2019_jslhr-l-19-0001 · Cited by 35 · see citing works
Ikegame, T., Bundo, M., Okada, N., Murata, Y., Koike, S., Sugawara, H., Saito, T., Ikeda, M., Owada, K., Fukunaga, M., et al. (2020) · Schizophrenia Bulletin · doi:10.1093/schbul/sbaa075 · Cited by 35 · see citing works
Genetic Approaches for Sports Performance: How Far Away Are We?
Joyner, M. J. (2019) · Sports Medicine · doi:10.1007/s40279-019-01164-z · Cited by 33 · see citing works
Arends, R. M., Pasman, J. A., Verweij, K. J. H., Derks, E. M., Gordon, S. D., Hickie, I. B., Thomas, N., Alıev, F., Zietsch, B. P., van der Zee, M. D., et al. (2021) · Addiction Biology · doi:10.1111/adb.13015 · Cited by 32 · see citing works
Polygenic Scores for Plasticity: A New Tool for Studying Gene–Environment Interplay
Johnson, R., Sotoudeh, R., & Conley, D. (2022) · Demography · doi:10.1215/00703370-9957418 · Cited by 33 · see citing works
Lehto, K., Hägg, S., Lu, D., Karlsson, R., Pedersen, N. L., & Mosing, M. A. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.10.016 · Cited by 34 · see citing works
- Authors
- Border, R., Johnson, E. C., Evans, L. M., Smolen, A., Berley, N., Sullivan, P. F., & Keller, M. C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2019-05-01
- Volume
- 176
- Issue
- 5
- Pages
- 376-387
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC6548317
- OpenAlex
- W2919957599
- Semantic Scholar
- 204d532eea4e3f20bc61ae2250587ad86fc82ebf
- Cited by
- 629
- References
- 57
- Citations by year
- 2026: 53 · 2025: 49 · 2024: 68 · 2023: 84 · 2022: 87 · 2021: 111 · 2020: 118 · 2019: 56 · 2017: 1
- FWCI
- 55.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- American Journal of Psychiatry (publishedVersion, other-oa)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (1532235, 1532236)
- Pfizer
- H. Lundbeck A/S
- National Institute of Mental Health (U01MH109528, R01MH100141, U01MH109536, T32MH016880)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, candidate genes, gene-environment interaction, genetic polymorphism, depression subtypes, childhood abuse, socioeconomic adversity, false positives, measurement error
- MeSH terms
- Psychological Trauma, Adverse Childhood Experiences, Major Depressive Disorder, Humans, Phenotype, Polymorphism, Genetic, Recurrence, Severity of Illness Index, Socioeconomic Factors, Reproducibility of Results, Genetic Association Studies, Gene-Environment Interaction
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
