A Systematic Review of Candidate Genes for Major Depression

Abstract

Background and Objectives: The aim of this systematic review was to analyse which candidate genes were examined in genetic association studies and their association with major depressive disorder (MDD). Materials and Methods: We searched PUBMED for relevant studies published between 1 July 2012 and 31 March 2019, using combinations of keywords: “major depressive disorder” OR “major depression” AND “gene candidate”, “major depressive disorder” OR “major depression” AND “polymorphism”. Synthesis focused on assessing the likelihood of bias and investigating factors that may explain differences between the results of studies. For selected gene list after literature overview, functional enrichment analysis and gene ontology term enrichment analysis were conducted. Results: 141 studies were included in the qualitative review of gene association studies focusing on MDD. 86 studies declared significant results (p < 0.05) for 172 SNPs in 85 genes. The 13 SNPs associations were confirmed by at least two studies. The 18 genetic polymorphism associations were confirmed in both the previous and this systematic analysis by at least one study. The majority of the studies (68.79 %) did not use or describe power analysis, which may have had an impact over the significance of their results. Almost a third of studies (N = 54) were conducted in Chinese Han population. Conclusion: Unfortunately, there is still insufficient data on the links between genes and depression. Despite the reported genetic associations, most studies were lacking in statistical power analysis, research samples were small, and most gene polymorphisms have been confirmed in only one study. Further genetic research with larger research samples is needed to discern whether the relationship is random or causal. Summations: This systematic review had summarized all reported genetic associations and has highlighted the genetic associations that have been replicated. Limitations: Unfortunately, most gene polymorphisms have been confirmed only once, so further studies are warranted for replicating these genetic associations. In addition, most studies included a small number of MDD cases that could be indicative for false positive. Considering that polymorphism loci and associations with MDD is also vastly dependent on interpersonal variation, extensive studies of gene interaction pathways could provide more answers to the complexity of MDD.

Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims

“…A multi-locus GWAS study demonstrated that several allelic variations in glutamatergic synaptic signaling, such as GRIK1, GRIK2, GRIK3, GRIN1, GRIN2A, GRIN2C or GRM7, were associated with MDD [77]. A subsequent systematic review revealed that several crucial candidate genes for MDD are involved in glutamate neurotransmission, [45]. Moreover, several studies found decreases in mRNA expression of NMDA and AMPA receptor subunits associated with schizophrenia in the frontal cortex [121][122][123].…”

“…Genetic variants of serotonergic, dopaminergic and adrenergic genes are the most extensively studied genes in relation to both depression and suicidal behavior; however, to date, only few candidate gene variants have been reliably associated with suicidality [43]. A recent meta-analysis identified novel depression-associated variants involved in the development and maintenance of cognitive processes [44]; moreover, a systematic review revealed that the most crucial candidate genes for major depressive disorder (MDD) are involved in glutamate neurotransmission, regulation of calcium channel activity and apoptosis [45]. A cell-type-specific methylome study pointed to the role of the innate immune responses via p75NTR/neurotrophic growth factor and Toll-like receptor signaling in MDD [46].…”

Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) – a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich

“…In addition, it has been of great interest to identify the specific determinants among such genetic influences, first in large general population samples and subsequently more narrowly defined smaller clinical samples. In this context, candidate gene studies have proposed a long list of common polymorphisms that are related to depressive disorders 19…”

Protein-coding mutation inAdcy3increases adiposity and alters emotional behaviors sex-dependently in rats

“…Nevertheless, genetic factors have been shown to play an important role in the development of both diseases. 5,6 Adenylate cyclase 3 (Adcy3) has been established as an important gene for both obesity and MDD, supported by both human [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] and rodent [22][23][24][25][26][27][28] studies. 29 ADCY3 is a plasma membraneassociated protein that catalyzes the synthesis of cAMP, a secondary messenger that has itself been linked to the development and treatment of obesity and MDD.…”