ArticleThe American journal of psychiatry2019
No Support for Historical Candidate Gene or Candidate Gene-by-Interaction Hypotheses for Major Depression Across Multiple Large Samples.
Article in The American journal of psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers, 15 of them syntheses that pooled it.
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Who cites it
253 citing papers in PubMed, 15 syntheses or guidelines pooled it.
- Biological and neurocognitive correlates of comorbid post-traumatic stress disorder and alcohol use disorder: a systematic review.European journal of psychotraumatology · 2026Pooled it
- Oxytocin dysfunction in severe mental illnesses following adverse childhood experiences: a systematic review.BMC psychiatry · 2026Pooled it
- Japanese Cohort Study Identifies an Association Between the Serotonin Transporter-Linked Polymorphic Region and Suicide Death.Neuropsychopharmacology reports · 2026Pooled it
- A systematic review of methylome-wide associations with anxiety disorders.Translational psychiatry · 2026Pooled it
- Genetic association studies in critically ill patients: a systematic review.EBioMedicine · 2025Pooled it
- The genetics of trichotillomania and excoriation disorder: A systematic review.Comprehensive psychiatry · 2024Pooled it
- Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers.The international journal of neuropsychopharmacology · 2023Pooled it
- Polygenicity of Comorbid Depression in Multiple Sclerosis.Neurology · 2023Pooled it
- The serotonin theory of depression: a systematic umbrella review of the evidence.Molecular psychiatry · 2023Pooled it
- Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review.Neuroscience and biobehavioral reviews · 2023Pooled it
- Differential Relations of Parental Behavior to Children's Early Executive Function as a Function of Child Genotype: A Systematic Review.Clinical child and family psychology review · 2022Pooled it
- A Systematic Review of Candidate Genes for Major Depression.Medicina (Kaunas, Lithuania) · 2022Pooled it
- Genetic Variants Associated With Resilience in Human and Animal Studies.Frontiers in psychiatry · 2022Pooled it
- A systematic review of gene-by-intervention studies of alcohol and other substance use.Development and psychopathology · 2021Pooled it
- Population genetic considerations for using biobanks as international resources in the pandemic era and beyond.BMC genomics · 2021Pooled it
- Novel GxE effects and resilience: A case:control longitudinal study of psychosocial stress with war-affected youth.PloS one · 2022Trial
- Identifying differential interactions of potentially traumatic experiences with genetic risk for posttraumatic stress disorder.European journal of psychotraumatology · 2026Article
- Effects of Serotonin Transporter Genotype and (Un)Predictable Maternal Separation on Affective, Cognitive, and Social Behaviors in Female Rats.Genes, brain, and behavior · 2026Article
- Integrating NRG1 and OXT Polymorphisms, Maternal Psychological Vulnerability, and Obstetric-Neonatal Outcomes: A Genotype-Phenotype Pilot Study.Journal of clinical medicine · 2026Article
- The choice-wide behavioral association study: data-driven identification of interpretable behavioral components.Nature communications · 2026Article
193 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
objectiveInterest 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.
methodsUtilizing 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).
resultsNo 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.
conclusionsThe 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.
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