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Psychiatric Genetics Jun 2023Neuroticism, alexithymia and emotion dysregulation are key traits and known risk factors for several psychiatric conditions. In this systematic review, the aim is to...
Neuroticism, alexithymia and emotion dysregulation are key traits and known risk factors for several psychiatric conditions. In this systematic review, the aim is to evaluate the genetic contribution to these psychological phenotypes. A systematic review of articles found in PubMed was conducted. Search terms included 'genetic', 'GWAS', 'neuroticism', 'alexithymia' and 'emotion dysregulation'. Risk of bias was assessed utilizing the STREGA checklist. Two hundred two papers were selected from existing literature based on the inclusion and exclusion criteria. Among these, 27 were genome-wide studies and 175 were genetic association studies. Single gene association studies focused on selected groups of genes, mostly involved in neurotransmission, with conflicting results. GWAS studies on neuroticism, on the other hand, found several relevant and replicated intergenic and intronic loci affecting the expression and regulation of crucial and well-known genes (such as DRD2 and CRHR1). Mutations in genes coding for trascriptional factors were also found to be associated with neuroticism (DCC, XKR6, TCF4, RBFOX1), as well as a noncoding regulatory RNA (LINC00461). On the other hand, little GWAS data are available on alexythima and emotional dysregulation.
Topics: Humans; Genetic Predisposition to Disease; Neuroticism; Genetic Association Studies; Phenotype; Genome-Wide Association Study
PubMed: 36729042
DOI: 10.1097/YPG.0000000000000335 -
Frontiers in Psychiatry 2022Resilience is broadly defined as the ability to maintain or regain functioning in the face of adversity and is influenced by both environmental and genetic factors. The...
Resilience is broadly defined as the ability to maintain or regain functioning in the face of adversity and is influenced by both environmental and genetic factors. The identification of specific genetic factors and their biological pathways underpinning resilient functioning can help in the identification of common key factors, but heterogeneities in the operationalisation of resilience have hampered advances. We conducted a systematic review of genetic variants associated with resilience to enable the identification of general resilience mechanisms. We adopted broad inclusion criteria for the definition of resilience to capture both human and animal model studies, which use a wide range of resilience definitions and measure very different outcomes. Analyzing 158 studies, we found 71 candidate genes associated with resilience. OPRM1 (Opioid receptor mu 1), NPY (neuropeptide Y), CACNA1C (calcium voltage-gated channel subunit alpha1 C), DCC (deleted in colorectal carcinoma), and FKBP5 (FKBP prolyl isomerase 5) had both animal and human variants associated with resilience, supporting the idea of shared biological pathways. Further, for OPRM1, OXTR (oxytocin receptor), CRHR1 (corticotropin-releasing hormone receptor 1), COMT (catechol-O-methyltransferase), BDNF (brain-derived neurotrophic factor), APOE (apolipoprotein E), and SLC6A4 (solute carrier family 6 member 4), the same allele was associated with resilience across divergent resilience definitions, which suggests these genes may therefore provide a starting point for further research examining commonality in resilience pathways.
PubMed: 35669264
DOI: 10.3389/fpsyt.2022.840120 -
Scientific Reports May 2021In addition to chronic infection with human papilloma virus (HPV) and exposure to environmental carcinogens, genetic and epigenetic factors act as major risk factors for...
In addition to chronic infection with human papilloma virus (HPV) and exposure to environmental carcinogens, genetic and epigenetic factors act as major risk factors for head and neck cancer (HNC) development and progression. Here, we conducted a systematic review in order to assess whether DNA hypermethylated genes are predictive of high risk of developing HNC and/or impact on survival and outcomes in non-HPV/non-tobacco/non-alcohol associated HNC. We identified 85 studies covering 32,187 subjects where the relationship between DNA methylation, risk factors and survival outcomes were addressed. Changes in DNA hypermethylation were identified for 120 genes. Interactome analysis revealed enrichment in complex regulatory pathways that coordinate cell cycle progression (CCNA1, SFN, ATM, GADD45A, CDK2NA, TP53, RB1 and RASSF1). However, not all these genes showed significant statistical association with alcohol consumption, tobacco and/or HPV infection in the multivariate analysis. Genes with the most robust HNC risk association included TIMP3, DCC, DAPK, CDH1, CCNA1, MGMT, P16, MINT31, CD44, RARβ. From these candidates, we further validated CD44 at translational level in an independent cohort of 100 patients with tongue cancer followed-up beyond 10 years. CD44 expression was associated with high-risk of tumor recurrence and metastasis (P = 0.01) in HPV-cases. In summary, genes regulated by methylation play a modulatory function in HNC susceptibility and it represent a critical therapeutic target to manage patients with advanced disease.
Topics: Carcinoma, Squamous Cell; DNA Methylation; Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Molecular Targeted Therapy
PubMed: 33976322
DOI: 10.1038/s41598-021-89476-x