ArticleBiological psychiatry2017
Genome-wide Regional Heritability Mapping Identifies a Locus Within the TOX2 Gene Associated With Major Depressive Disorder.
Article in Biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Research trend of epigenetics and depression: adolescents' research needs to strengthen.Frontiers in neuroscience · 2023Pooled it
- Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled it
- The long noncoding RNA Peanut (Gm11454) biases progenitors towards neurogenesis and rod photoreceptor differentiation during postnatal retinal development.Developmental biology · 2026Article
- Optimization of potential targets for antidepressant Chinese medicines: AI and multi-omics methods.Chinese medicine · 2026Review
- The long noncoding RNAbioRxiv : the preprint server for biology · 2025Article
- Non-pharmacological therapeutic paradigms in stress-induced depression: from novel therapeutic perspective with focus on cell-based strategies.Acta neuropsychiatrica · 2025Review
- Drug-drug interaction of paroxetine on olanzapine and initial dosage optimization in patients with major depressive disorder based on population pharmacokinetics.Frontiers in psychiatry · 2025Article
- Integrating mitoepigenetics into research in mood disorders: a state-of-the-art review.Frontiers in physiology · 2024Review
- Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.Signal transduction and targeted therapy · 2023Review
- Correlation between variants of the CREB1 and GRM7 genes and risk of depression.BMC psychiatry · 2023Article
- Association Between Single Nucleotide Polymorphisms Within lncRNA NONHSAT102891 and Depression Susceptibility in a Chinese Population.Neuropsychiatric disease and treatment · 2023Article
- Review
- ElevatedProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Shared genetic loci between depression and cardiometabolic traits.PLoS genetics · 2022Article
- The Molecular Basis of Depression: Implications of Sex-Related Differences in Epigenetic Regulation.Frontiers in molecular neuroscience · 2021Article
- Article
- Machine learning in major depression: From classification to treatment outcome prediction.CNS neuroscience & therapeutics · 2018Review
- Global long non-coding RNA expression in the rostral anterior cingulate cortex of depressed suicides.Translational psychiatry · 2018Article
- A genetic perspective on the relationship between eudaimonic -and hedonic well-being.Scientific reports · 2018Article
- Genetic risk of major depressive disorder: the moderating and mediating effects of neuroticism and psychological resilience on clinical and self-reported depression.Psychological medicine · 2018Article
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Authors and funding
40 authors at 17 institutions in 7 countries.
Funding
Abstract
backgroundMajor depressive disorder (MDD) is the second largest cause of global disease burden. It has an estimated heritability of 37%, but published genome-wide association studies have so far identified few risk loci. Haplotype-block-based regional heritability mapping (HRHM) estimates the localized genetic variance explained by common variants within haplotype blocks, integrating the effects of multiple variants, and may be more powerful for identifying MDD-associated genomic regions.
methodsWe applied HRHM to Generation Scotland: The Scottish Family Health Study, a large family- and population-based Scottish cohort (N = 19,896). Single-single nucleotide polymorphism (SNP) and haplotype-based association tests were used to localize the association signal within the regions identified by HRHM. Functional prediction was used to investigate the effect of MDD-associated SNPs within the regions.
resultsA haplotype block across a 24-kb region within the TOX2 gene reached genome-wide significance in HRHM. Single-SNP- and haplotype-based association tests demonstrated that five of nine genotyped SNPs and two haplotypes within this block were significantly associated with MDD. The expression of TOX2 and a brain-specific long noncoding RNA RP1-269M15.3 in frontal cortex and nucleus accumbens basal ganglia, respectively, were significantly regulated by MDD-associated SNPs within this region. Both the regional heritability and single-SNP associations within this block were replicated in the UK-Ireland group of the most recent release of the Psychiatric Genomics Consortium (PGC), the PGC2-MDD (Major Depression Dataset). The SNP association was also replicated in a depressive symptom sample that shares some individuals with the PGC2-MDD.
conclusionsThis study highlights the value of HRHM for MDD and provides an important target within TOX2 for further functional studies.
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