GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia

Lin, Yi; Wang, Chia-Chun; Chen, Cho-Yi

doi:10.3390/genes12101506

Cited by 9 publications

(8 citation statements)

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“…For example, Santiago et al reported that changes in cortisol are the modulator between sleep disturbances and depression ( 6 ). Lin et al found 719 shared genes between MD and insomnia, which provide insight into the genetic substrates in depression individuals' comorbid insomnia symptoms ( 7 ). Yan et al proposed that dysfunctional glymphatic pathway may serve as a bridge between sleep disturbance and depression ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

The Function and Structure of Precuneus Is Associated With Subjective Sleep Quality in Major Depression

Zhang

2022

Front. Psychiatry

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BackgroundPoor sleep quality is related to depression. However, the investigation of the neural basis for poor sleep quality in individuals with major depression (MD) is limited.MethodsResting state functional and structural MRI data were derived from 114 MD individuals and 74 normal controls (NCs). Fractional amplitude of low-frequency fluctuation (fALFF) and gray matter volume (GMV) were used to measure function and structure of the brain. Pittsburgh Sleep Quality Index (PSQI) was performed to evaluate subjective sleep quality. Correlations were carried out to investigate links of PSQI score with brain imaging indices in MD and NCs, separately. We also examined the differences in fALFF and GMV of brain regions related to PSQI score between MD and NCs.ResultsIn contrast to NCs, MD individuals had higher PSQI score. The higher PSQI score was associated with lower fALFF and lower GMV in bilateral precuneus in MD individuals. Moreover, the MD individuals exhibited increased fALFF in bilateral precuneus compared with NCs. However, the correlation between subjective sleep quality and neuroimaging parameters was not significant in NCs.ConclusionThe implication of these findings is that the function and structure of precuneus provides a neural basis for subjective poor sleep quality in MD. Understanding this may lead to better intervention of depression and associated sleep complaints.

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Section: Introductionmentioning

confidence: 99%

The Function and Structure of Precuneus Is Associated With Subjective Sleep Quality in Major Depression

Zhang

2022

Front. Psychiatry

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“…The next strongest signal observed on Butyrophilin (BTN) family genes was another common finding in the genome-wide cross-trait meta-analysis of DCC and MDD (index SNP rs67777156, P meta = 2.20 × 10 −15 ). Among its related pathways are Butyrophilin (BTN) family interactions and Class I MHC-mediated antigen processing and presentation ( 20 ).…”

Section: Resultsmentioning

confidence: 99%

“…Reactome enrichment of HATs acetylate histones, HDACs deacetylate histones, HDMs demethylate histones, DNA methylation, and developmental biology together suggested the effects of both genetic and epigenetics on DCC/MDD and DCC/neuroticism. A study has revealed the shared pathway including DNA methylation between MDD and Insomnia ( 20 ). Inhibition of DNA methyltransferase 3a by polyphenol from coffee was also confirmed ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

“…The GWAS summary statistics of insomnia and neuroticism items scores are available at https://ctg.cncr.nl/software/summary_ statistics. We also could download GWAS summary statistics of AD (71,880 cases and 383,378 controls), BIP (20,352 and Project MinE, an international collaboration of investigators aiming to unravel the genetic basis of ALS, respectively (Available online: http://databrowser.projectmine.com/). For all the metaanalyses of GWAS included in this study, we only focused on the data generated from the analysis of individuals from Europe.…”

Section: Study Design and Data Sourcesmentioning

confidence: 99%

“…For different neuropsychiatric diseases, heritability has been estimated at varying between 50 and 80% (13)(14)(15)(16)(17). Recently, A GWAS of caffeine consumption in coffee consumers detected one susceptibility loci rs13107325 (SLC39A8) (18), which was also significantly identified in the GWAS of mental diseases (19,20), suggesting potential shared genetic components between caffeine coffee consumption and neuropsychiatric diseases. Nevertheless, coffee is more than caffeine, and many other substances were found in amounts much more than that of caffeine and were thought to be responsible for health conditions (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis

et al. 2022

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Coffee or caffeine consumption has been associated with neuropsychiatric disorders, implying a shared etiology. However, whether these associations reflect causality remains largely unknown. To understand the genetic structure of the association between decaffeinated coffee consumption (DCC) and neuropsychiatric traits, we examined the genetic correlation, causality, and shared genetic structure between DCC and neuropsychiatric traits using linkage disequilibrium score regression, bidirectional Mendelian randomization (MR), and genome-wide cross-trait meta-analysis in large GWAS Consortia for coffee consumption (N = 329,671) and 13 neuropsychiatric traits (sample size ranges from 36,052 to 500,199). We found strong positive genetic correlations between DCC and lifetime cannabis use (LCU; Rg = 0.48, P = 8.40 × 10−19), alcohol use disorder identification test (AUDIT) total score (AUDIT_T; Rg = 0.40, P = 4.63 × 10−13), AUDIT_C score (alcohol consumption component of the AUDIT; Rg = 0.40, P = 5.26 × 10−11), AUDIT_P score (dependence and hazardous-use component of the AUDIT; Rg = 0.28, P = 1.36 × 10−05), and strong negative genetic correlations between DCC and neuroticism (Rg = −0.15, P = 7.27 × 10−05), major depressed diseases (MDD; Rg = −0.15, P = 0.0010), and insomnia (Rg= −0.15, P = 0.0007). In the cross-trait meta-analysis, we identified 6, 5, 1, 1, 2, 31, and 27 shared loci between DCC and Insomnia, LCU, AUDIT_T, AUDIT_C, AUDIT_P, neuroticism, and MDD, respectively, which were mainly enriched in bone marrow, lymph node, cervix, uterine, lung, and thyroid gland tissues, T cell receptor signaling pathway, antigen receptor-mediated signaling pathway, and epigenetic pathways. A large of TWAS-significant associations were identified in tissues that are part of the nervous system, digestive system, and exo-/endocrine system. Our findings further indicated a causal influence of liability to DCC on LCU and low risk of MDD (odds ratio: 0.90, P = 9.06 × 10−5 and 1.27, P = 7.63 × 10−4 respectively). We also observed that AUDIT_T and AUDIT_C were causally related to DCC (odds ratio: 1.83 per 1-SD increase in AUDIT_T, P = 1.67 × 10−05, 1.80 per 1-SD increase in AUDIT_C, P = 5.09 × 10−04). Meanwhile, insomnia and MDD had a causal negative influence on DCC (OR: 0.91, 95% CI: 0.86–0.95, P = 1.51 × 10−04 for Insomnia; OR: 0.93, 95% CI: 0.89–0.99, P = 6.02 × 10−04 for MDD). These findings provided evidence for the shared genetic basis and causality between DCC and neuropsychiatric diseases, and advance our understanding of the shared genetic mechanisms underlying their associations, as well as assisting with making recommendations for clinical works or health education.

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Genomic and epigenomic signature at the branch-point among genome, phenome, and sexome in health and disease: A multiomics approach

Gemmati¹,

Tisato²

2023

Principles of Gender-Specific Medicine

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GWAS Meta-Analysis Reveals Shared Genes and Biological Pathways between Major Depressive Disorder and Insomnia

Cited by 9 publications

References 93 publications

The Function and Structure of Precuneus Is Associated With Subjective Sleep Quality in Major Depression

The Function and Structure of Precuneus Is Associated With Subjective Sleep Quality in Major Depression

Shared Genetics and Causality Between Decaffeinated Coffee Consumption and Neuropsychiatric Diseases: A Large-Scale Genome-Wide Cross-Trait Analysis and Mendelian Randomization Analysis

Genomic and epigenomic signature at the branch-point among genome, phenome, and sexome in health and disease: A multiomics approach

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