Epigenetic clock analysis reveals increased plasma cystatin C levels based on DNA methylation in major depressive disorder

Tanifuji, Takaki; Okazaki, Kenji; Otsuka, Ikuo; Mouri, Kentaro; Horai, Tadasu; Shindo, Ryota; Shirai, Toshiyuki; Hishimoto, Akitoyo

doi:10.1016/j.psychres.2023.115103

Cited by 14 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, low lung function that disrupts the exchange of oxygen and carbon dioxide could engender both conditions [ 38 ], causing metabolic dysregulation in brain cells and ultimately triggering depressive symptoms [ 39 ]. Moreover, the increased risk of depression ascribed to impaired lung function might be partially explained by the deterioration in the liver and renal functions, in line with prior studies [ 13 , 14 , 40 , 41 ]. For instance, a cohort study involving more than 370,000 participants revealed a significant association between liver function markers, such as ALT, TBIL, ALB, TP, GGT, and ALP, and an elevated risk of lung disease [ 13 ].…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants

Hu,

Liu,

Jia

2024

BMC Med

View full text Add to dashboard Cite

Background Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. Methods This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank. Lung function was assessed through the forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1). Cox proportional hazard models were applied to estimate the associations between lung function and incident depression. Mediation analyses were fitted to investigate the potential mediating role of biomarkers and metabolites in the association. Results A total of 9514 participants (3.4%) developed depression during a median follow-up of 13.91 years. Individuals in the highest quartile had a lower risk of depression (FVC % predicted: HR = 0.880, 95% CI = 0.830–0.933; FEV1% predicted: HR = 0.854, 95% CI = 0.805–0.905) compared with those in the lowest quartile of the lung function indices. Additionally, the restricted cubic splines suggested lung function indices had reversed J-shaped associations with incident depression (nonlinear P < 0.05 for FVC % predicted and FEV1% predicted). Impaired lung function yielded similar risk estimates (HR = 1.124, 95% CI = 1.074–1.176). Biomarkers involving systemic inflammation, erythrocytes, and liver and renal function may be potential mediators in the lung function-depression association. Conclusions This study revealed that the higher risk of developing depression was associated with impaired lung function. Also, the association might be partially mediated by biomarkers including systemic inflammation, erythrocytes, and liver and renal function, though these mediation findings should be interpreted with caution due to potential temporal ambiguity.

show abstract

Section: Discussionsupporting

confidence: 85%

“…Also, a MR study supported a causal relationship between lung diseases and renal function [ 14 ]. Remarkably, the relationship between liver and renal dysfunction and depression has been well established [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants

Hu,

Liu,

Jia

2024

BMC Med

View full text Add to dashboard Cite

show abstract

“…For example, the pathophysiology of schizophrenia, as well as alcohol dependency, has been linked to dysfunction of central dopaminergic neurotransmission [29]. MDD is also associated with DNA methylation changes that may regulate gene expression [30]. However, the relationship between alcohol‐related DNA methylation and the risk of psychiatric disorders is not clear, and no reported study has investigated whether alcohol‐related DNA methylation is causally associated with psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

Alcohol drinking, DNA methylation and psychiatric disorders: A multi‐omics Mendelian randomization study to investigate causal pathways

Shi,

Li,

Yao

et al. 2024

Addiction

View full text Add to dashboard Cite

Background and aimsWhether alcohol‐related DNA methylation has a causal effect on psychiatric disorders has not been investigated. Furthermore, a comprehensive investigation into the causal relationship and underlying mechanisms linking alcohol consumption and psychiatric disorders has been lacking. This study aimed to evaluate the causal effect of general alcohol intake and pathological drinking behaviors on psychiatric disorders, alcohol‐associated DNA methylation on gene expression and psychiatric disorders, and gene expression on psychiatric disorders.DesignTwo‐sample design Mendelian randomization (MR) analysis. Various sensitivity and validation analyses, including colocalization analysis, were conducted to test the robustness of the results.SettingGenome‐wide association study (GWAS) data mainly from GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), Genetics of DNA Methylation Consortium (GoDMC) and Psychiatric Genomics Consortium (PGC) with European ancestry.ParticipantsThe GWAS summary data on general alcohol intake (drinks per week, n = 941 280), pathological drinking behaviors (including alcohol use disorder [AUD, n = 313 959] and problematic alcohol use [PAU, n = 435 563]) and psychiatric disorders (including schizophrenia, major depressive disorder and bipolar disorder, n = 51 710–500 199) were included. Alcohol‐related DNA methylation CpG sites (n = 9643) and mQTL data from blood (n = 27 750) and brain (n = 1160), BrainMeta v2 and GTEx V8 eQTL summary data (n = 73–2865) were also included.MeasurementsGenetic variants were selected as instrumental variables for exposures, including drinks per week, AUD, PAU, alcohol‐related DNA methylation CpG sites (mQTL) and genes selected (eQTL).FindingsPathological drinking behaviors were associated with an increased risk of psychiatric disorders after removing outliers or controlling for alcohol consumption. MR analysis identified 10 alcohol‐related CpG sites with colocalization evidence that were causally associated with psychiatric disorders (P = 1.65 × 10−4–7.52 × 10−22). Furthermore, the expression of genes (RERE, PTK6, GATAD2B, COG8, PDF and GAS5) mapped to these CpG sites in the brain, led by the cortex, were significantly associated with psychiatric disorders (P = 1.19 × 10−2–3.51 × 10−7).ConclusionsPathological drinking behavior and alcohol‐related DNA methylation appear to have a causal effect on psychiatric disorders. The expression of genes regulated by the alcohol‐related DNA methylation sites may underpin this association.

show abstract

Biological aging analysis based on DNA methylation status for social anxiety disorder

Noguchi,

Shirai,

Suda

et al. 2024

Neuropsychopharm Rep

View full text Add to dashboard Cite

AimSocial anxiety disorder (SAD) is a common disorder characterized by excessive fear of scrutiny and embarrassment, leading to severe distress and avoidance behaviors or dysfunctions. SAD and other relevant diseases have been reported to be associated with a higher risk of aging‐related diseases, such as Alzheimer's disease, Parkinson's disease, and diabetes mellitus. Recently, epigenetic clock analysis, which measures biological aging based on comprehensive DNA methylation (DNAm) status, has been widely conducted. We conducted epigenetic clock analyses in patients with SAD and controls, examining various epigenetic age acceleration and DNAm‐based predictive values of aging‐related proteins (GrimAge components and GrimAge2 components), including leptin level.MethodsWe used the publicly available DNAm dataset, GSE164056, which consists of 66 patients with SAD and 77 controls of Caucasian descent aged between 18 and 50 years. We conducted regression analyses investigating the association between SAD and various indices of epigenetic aging, using age and sex as covariates.ResultsNone of the epigenetic clocks showed significant differences in age acceleration. Of the DNAm‐based predictive values of aging‐related proteins, leptin level in GrimAge components (q = 0.0123) and GrimAge2 components (q = 0.0123) were significantly lower in patients with SAD than in controls.ConclusionsThe results of this study suggested that leptin may be involved in SAD pathogenesis as an aging‐related protein. Therefore, further studies with different designs are required.

show abstract

Epigenetic clock analysis reveals increased plasma cystatin C levels based on DNA methylation in major depressive disorder

Cited by 14 publications

References 47 publications

Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants

Association and biological pathways between lung function and incident depression: a prospective cohort study of 280,032 participants

Alcohol drinking, DNA methylation and psychiatric disorders: A multi‐omics Mendelian randomization study to investigate causal pathways

Biological aging analysis based on DNA methylation status for social anxiety disorder

Contact Info

Product

Resources

About