ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2019
Integrative analyses of major histocompatibility complex loci in the genome-wide association studies of major depressive disorder.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Investigating the relationship between depression and breast cancer: observational and genetic analyses.BMC medicine · 2023Pooled it
- Independent replications and integrative analyses confirm TRANK1 as a susceptibility gene for bipolar disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Pooled it
- Optimization of potential targets for antidepressant Chinese medicines: AI and multi-omics methods.Chinese medicine · 2026Review
- B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression.Frontiers in cellular neuroscience · 2024Review
- Integrating eQTL and GWAS data characterises established and identifies novel migraine risk loci.Human genetics · 2023Article
- Neurobiologically Based Stratification of Recent-Onset Depression and Psychosis: Identification of Two Distinct Transdiagnostic Phenotypes.Biological psychiatry · 2022Article
- Comprehensive and integrative analyses identify TYW5 as a schizophrenia risk gene.BMC medicine · 2022Article
- Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature.Brain sciences · 2021Review
- A Human-Specific Schizophrenia Risk Tandem Repeat Affects Alternative Splicing of a Human-Unique Isoform AS3MTd2d3 and Mushroom Dendritic Spine Density.Schizophrenia bulletin · 2021Article
- Transcriptomic analyses of humans and mice provide insights into depression.Zoological research · 2020Article
- Convergent Functional Genomics approach to prioritize molecular targets of risk in early life stress-related psychiatric disorders.Brain, behavior, & immunity - health · 2020Review
- Immune dysregulation in depression: Evidence from genome-wide association.Brain, behavior, & immunity - health · 2020Article
- Identification of a functional human-unique 351-bp Alu insertion polymorphism associated with major depressive disorder in the 1p31.1 GWAS risk loci.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data.Translational psychiatry · 2020Article
- The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function, and mushroom dendritic spine.Molecular psychiatry · 2020Article
- Depression in patients with spondyloarthritis: prevalence, incidence, risk factors, mechanisms and management.Therapeutic advances in musculoskeletal disease · 2020Review
- The depression GWAS risk allele predicts smaller cerebellar gray matter volume and reduced SIRT1 mRNA expression in Chinese population.Translational psychiatry · 2019Article
- Identification of the primate-specific gene BTN3A2 as an additional schizophrenia risk gene in the MHC loci.EBioMedicine · 2019Article
- Association ofFrontiers in genetics · 2019Article
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent European genome-wide association studies (GWAS) have revealed strong statistical correlations between MDD and numerous zero-to-high linked variants in the genomic region containing major histocompatibility complex (MHC) genes (MHC region), but the underlying biological mechanisms are still unclear. To better understand the roles of this genomic region in the neurobiology of MDD, we applied a convergent functional genomics approach to integrate GWAS data of MDD relevant biological phenotypes, gene-expression analyses results obtained from brain samples, and genetic analyses of independent Chinese MDD samples. We observed that independent MDD risk variants in the MHC region were also significantly associated with the relevant biological phenotypes in the predicted directions, including the emotional and cognitive-related phenotypes. Gene-expression analyses further revealed that mRNA expression levels of several MHC region genes in the human brain were associated with MDD risk SNPs and diagnostic status. For instance, a brain-enriched gene ZNF603P consistently showed lower mRNA levels in the individuals carrying MDD risk alleles and in MDD patients. Remarkably, we further found that independent MDD risk SNPs in the MHC region likely converged to affect the mRNA level(s) of the same gene(s), and Europeans and Han Chinese populations have a substantial shared genetic and molecular basis underlying MDD risk associations in the MHC region. These results highlighted several potential pivotal genes at the MHC region in the pathogenesis of MDD. Their common impacts on multiple psychiatric relevant phenotypes also implicated the neurological processes shared by different psychological processes, such as mood and/or cognition, shedding lights on their potential biological mechanisms.
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