ArticleTranslational psychiatry2019
The genetics of depression: successful genome-wide association studies introduce new challenges.
Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Genome-wide association meta-analysis and rare copy number variant analysis of treatment-resistant depression.Molecular psychiatry · 2025Pooled it
- Body mass index interacts with a genetic-risk score for depression increasing the risk of the disease in high-susceptibility individuals.Translational psychiatry · 2022Pooled it
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- [Embryonic origin of temperament: notochord and early signaling].Revista medica del Instituto Mexicano del Seguro Social · 2026Review
- The relevance of phenotypic definition in treatment resistant forms of major depressive disorder: a narrative review.Frontiers in pharmacology · 2026Review
- Childhood maltreatment and adult diseases in the general population: the mediating role of smoking and overweight in a time-sequence design.BMC public health · 2025Article
- Increased individual variability in functional connectivity of the default mode network and its genetic correlates in major depressive disorder.Scientific reports · 2025Article
- Factors Associated with the Development of Depression and the Influence of Obesity on Depressive Disorders: A Narrative Review.Biomedicines · 2024Review
- Identification of a strong genetic risk factor for major depressive disorder in the human virome.iScience · 2024Article
- Genetic influences on depression and selection into adverse life experiences.Social science & medicine (1982) · 2024Article
- Using an Interpretable Amino Acid-Based Machine Learning Method to Enhance the Diagnosis of Major Depressive Disorder.Journal of clinical medicine · 2024Article
- Menin Reduces Parvalbumin Expression and is Required for the Anti-Depressant Function of Ketamine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Investigating the genetic relationship of intracranial and subcortical brain volumes with depression and other psychiatric disorders.Imaging neuroscience (Cambridge, Mass.) · 2024Article
- The nucleus accumbens in reward and aversion processing: insights and implications.Frontiers in behavioral neuroscience · 2024Review
- Shared genetic architecture highlights the bidirectional association between major depressive disorder and fracture risk.General psychiatry · 2024Article
- Evaluating 17 methods incorporating biological function with GWAS summary statistics to accelerate discovery demonstrates a tradeoff between high sensitivity and high positive predictive value.Communications biology · 2023Article
- Polygenic predisposition, sleep duration, and depression: evidence from a prospective population-based cohort.Translational psychiatry · 2023Article
- Exome-wide association study of treatment-resistant depression suggests novel treatment targets.Scientific reports · 2023Article
- Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Updated Results From a Prospective, Longitudinal Study.Biological psychiatry global open science · 2023Article
- Stress-related exposures amplify the effects of genetic susceptibility on depression and anxiety.Translational psychiatry · 2023Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recent successful genome-wide association studies (GWASs) for depression have yielded more than 80 replicated loci and brought back the excitement that had evaporated during the years of negative GWAS findings. The identified loci provide anchors to explore their relevance for depression, but this comes with new challenges. Using the watershed model of genotype-phenotype relationships as a conceptual aid and recent genetic findings on other complex phenotypes, we discuss why it took so long and identify seven future challenges. The biggest challenge involves the identification of causal mechanisms since GWAS associations merely flag genomic regions without a direct link to underlying biological function. Furthermore, the genetic association with the index phenotype may also be part of a more extensive causal pathway (e.g., from variant to comorbid condition) or be due to indirect influences via intermediate traits located in the causal pathways to the final outcome. This challenge is highly relevant for depression because even its narrow definition of major depressive disorder captures a heterogeneous set of phenotypes which are often measured by even more broadly defined operational definitions consisting of a few questions (minimal phenotyping). Here, Mendelian randomization and future discovery of additional genetic variants for depression and related phenotypes will be of great help. In addition, reduction of phenotypic heterogeneity may also be worthwhile. Other challenges include detecting rare variants, determining the genetic architecture of depression, closing the "heritability gap", and realizing the potential for personalized treatment. Along the way, we identify pertinent open questions that, when addressed, will advance the field.
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