SynthesisPloS one2018
Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder.
Synthesis in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Genetics, epigenetics, and neurobiology of childhood-onset depression: an umbrella review.Molecular psychiatry · 2024Pooled it
- Identifying genome-by-childhood trauma interactions for depression using a forest-based approach in the UK Biobank and Adolescent Brain Cognitive Development Study.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Polygenic scores in the study of gene-environment interplay and stress-related psychopathology.Frontiers in psychiatry · 2026Review
- Intergenerational continuity of depressive symptoms: genetic and environmental pathways.Psychological medicine · 2025Article
- Endophenotype 2.0: updated definitions and criteria for endophenotypes of psychiatric disorders, incorporating new technologies and findings.Translational psychiatry · 2024Review
- The Interaction of Polygenic Susceptibility to Stress and Childhood Adversity Dimensions Predicts Longitudinal Trajectories of Stress-Sensitivity.Stress and health : journal of the International Society for the Investigation of Stress · 2024Article
- Investigating the shared genetic architecture between depression and subcortical volumes.Nature communications · 2024Article
- Estimating the direct effects of the genetic liabilities to bipolar disorder, schizophrenia, and behavioral traits on suicide attempt using a multivariable Mendelian randomization approach.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Association of polygenic scores for depression and neuroticism with perceived stress in daily life during a long-lasting stress period.Genes, brain, and behavior · 2023Article
- To what extent do social support and mastery mediate the association between childhood maltreatment and depression? A sequential causal mediation analysis.Epidemiology and psychiatric sciences · 2022Article
- Analysis of the effect of daily stress on the skin and search for genetic loci involved in the perceived stress of an individual.Skin health and disease · 2022Article
- The stressed synapse 2.0: pathophysiological mechanisms in stress-related neuropsychiatric disorders.Nature reviews. Neuroscience · 2022Review
- Little Evidence of Modified Genetic Effect of rs16969968 on Heavy Smoking Based on Age of Onset of Smoking.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021Article
- The Role of Protein SUMOylation in the Pathogenesis of Atherosclerosis.Journal of clinical medicine · 2019Review
- Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland.Translational psychiatry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.