The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

/pdf/integrative-analysis-of-111-reference-human-epigenomes-4bavnjaon6.pdf

Integrative analysis of 111 reference human epigenomes

The genomes of many animals, plants and fungi are tagged by methylation of DNA cytosine. To understand the biological significance of this epigenetic mark it is essential to know where in the genome it is located. New techniques are making it easier to map DNA methylation patterns on a large scale and the results have already provided surprises. In particular, the conventional view that DNA methylation functions predominantly to irreversibly silence transcription is being challenged. Not only is promoter methylation often highly dynamic during development, but many organisms also seem to target DNA methylation specifically to the bodies of active genes.

https://birdlab.bio.ed.ac.uk/bird/sites/sbsweb2.bio.ed.ac.uk.bird/files/20.pdf

DNA methylation landscapes: provocative insights from epigenomics

To gain insight into the function of DNA methylation at cis-regulatory regions and its impact on gene expression, we measured methylation, RNA polymerase occupancy and histone modifications at 16,000 promoters in primary human somatic and germline cells. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in male gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes are methylated in somatic cells, suggesting additional functional selection. These results show that promoter sequence and gene function are major predictors of promoter methylation states. Moreover, we observe that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation.

Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome.

http://www.uniroma2.it/didattica/Genomica_BTI/deposito/Mamm_Epigenome_rev_Cell.pdf

The mammalian epigenome.

Abstract Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with presence and severity of suicidal ideation were found within 18 and 3 co-expressed modules respectively (p < 0.05), not explained by severity of depression. Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified, and tested using RNA-seq data from postmortem brain that revealed gene expression differences in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity is associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability.

/pdf/functional-architecture-of-brain-and-blood-transcriptome-42yymyez.pdf

Functional Architecture of Brain and Blood Transcriptome Delineate Biological Continuity Between Suicidal Ideation and Suicide

Background: Complementary and integrative health (CIH) interventions show promise in improving overall wellness and engaging Veterans at risk of suicide. Methods: An intensive 4-week telehealth CIH intervention programming was delivered motivated by the COVID-19 pandemic, and outcomes were measured pre–post program completion. Results: With 93% program completion (121 Veterans), significant reduction in depression and posttraumatic stress disorder symptoms were observed pre–post telehealth CIH programing, but not in sleep quality. Improvements in pain symptoms, and stress management skills were observed in Veterans at risk of suicide. Discussion: Telehealth CIH interventions show promise in improving mental health symptoms among at-risk Veterans, with great potential to broaden access to care toward suicide prevention.

JICM-2022-0614-ver9-Ganesh_3P 127..130

Abstract The COVID-19 pandemic altered work environments of nurses, yielding high rates of stress and burnout. Potential protective factors, including effective sleep, may influence psychological health and wellbeing. Evidence about sleep in nurses may help develop interventions that mitigate burnout and poor psychological outcomes. A cross sectional survey was distributed across three hospitals to nurses in New York City (NYC). During the first wave of the pandemic (March–April 2020), NYC had the highest incidence of laboratory-confirmed COVID-19 cases (915/100 000) and half of all COVID-related deaths nationwide. Multivariable logistic regression was used to determine associations between Pittsburgh Sleep Quality Index (PSQI) global sleep score, PSQI sleep dimensions, and psychological health (burnout, depression, anxiety, and compassion fatigue), unadjusted and then controlling for individual and professional characteristics. More than half of the participants reported burnout (64%), depression, (67%), and anxiety (77%). Eighty percent of participants had PSQI global scores >5 (poor sleep) (mean 9.27, SD 4.14). Respondents reporting good sleep (PSQI ≤ 5) had over five times the odds of no burnout (OR: 5.65, 95% CI: 2.60, 12.27); increased odds of screening negative for depression (OR: 6.91, 95% CI: 3.24, 14.72), anxiety (OR: 10.75, 95% CI: 4.22, 27.42), and compassion fatigue (OR: 7.88, 95% CI: 1.97, 31.51). Poor subjective sleep quality PSQI subcomponent was associated with burnout (OR: 2.21, 95% CI: 1.41, 3.48) but sleep duration subcomponent was not (OR: 0.84, 95% CI: 0.59, 1.19). Daytime dysfunction was significantly associated with all psychological outcomes. Sleep disturbances and medications yielded higher anxiety odds. Overall, sleep quality appears more strongly related to burnout than sleep duration in nurses working during the COVID-19 pandemic. Sleep interventions should target individual sleep dimensions in nurses.

/pdf/assessing-sleep-health-dimensions-in-frontline-registered-1l74mynd.pdf

Assessing sleep health dimensions in frontline registered nurses during the COVID-19 pandemic: implications for psychological health and wellbeing

Background: Complementary and integrative health (CIH) interventions show promise in improving overall wellness and engaging Veterans at risk of suicide. Methods: An intensive 4-week telehealth CIH intervention programming was delivered motivated by the COVID-19 pandemic, and outcomes were measured pre–post program completion. Results: With 93% program completion (121 Veterans), significant reduction in depression and post-traumatic stress disorder symptoms were observed pre–post telehealth CIH programing, but not in sleep quality. Improvements in pain symptoms, and stress management skills were observed in Veterans at risk of suicide. Discussion: Telehealth CIH interventions show promise in improving mental health symptoms among at-risk Veterans, with great potential to broaden access to care toward suicide prevention.

Delivery of Telehealth Complementary and Integrated Health Interventions Improves Mental Health and Overall Wellness to Broaden Veterans' Access to Care

Fatemeh Haghighi

Papers

Functional Architecture of Brain and Blood Transcriptome Delineate Biological Continuity Between Suicidal Ideation and Suicide

JICM-2022-0614-ver9-Ganesh_3P 127..130

Assessing sleep health dimensions in frontline registered nurses during the COVID-19 pandemic: implications for psychological health and wellbeing

Delivery of Telehealth Complementary and Integrated Health Interventions Improves Mental Health and Overall Wellness to Broaden Veterans' Access to Care

Role of Peripheral Inflammation in Risk of Suicide