A compendium of chromatin contact maps reveals spatially active regions in the human genome

The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues. We also discover genomic regions that exhibit unusually high levels of local chromatin interactions. These frequently interacting regions (FIREs) are enriched for super-enhancers and are near tissue specifically expressed genes. They display strong tissue-specificity in local chromatin interactions. Additionally, FIRE formation is partially dependent on CTCF and the Cohesin complex. We further show that FIREs can help annotate the function of non-coding sequence variants

Interactions between the FTO rs9939609 polymorphism, body mass index, and lifestyle-related factors on metabolic syndrome risk

Whether the FTO polymorphisms interact with environmental factors has not yet been evaluated in associations with metabolic syndrome (MS) risk. The present study investigated the association of the FTO rs9939609 genotypes, body mass index (BMI), and lifestyle-related factors including smoking, alcohol drinking, physical activity, and diet with MS incidence. A population-based prospective cohort study comprised 3,504 male and female Koreans aged 40 to 69 years. At the beginning of the study, all individuals were free of MS and known cardiovascular disease. Incident cases of MS were identified by biennial health examinations during a follow-up period from April 17, 2003 to April 15, 2009. Pooled logistic regression analysis was applied to obtain relative odds (RO) of MS with its 95% confidence interval (CI). After controlling for potential MS risk factors, we observed no association between the rs9939609 genotypes and MS incidence. In analysis stratified by BMI, however, carriers with the FTO risk allele whose BMI is 29 kg/m2 or greater showed an approximately 6-fold higher RO (95% CI: 3.82 to 9.30) compared with non-carriers with BMI less than 25 kg/m2. In particular, the association between the rs9939609 variants and MS risk was significantly modified by high BMI (P-value for interaction < 0.05). Such significant interaction appeared in associations with central obesity and high blood pressure among the MS components. Because carriers of the FTO risk alleles who had BMI of 29 kg/m2 or greater are considered a high risk population, we suggest that they may need intensive weight loss regimens to prevent MS development

Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19

Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1 beta-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1 beta-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19

Associations of green tea, coffee, and soft drink consumption with longitudinal changes in leukocyte telomere length

Abstract Whether beverage consumption is associated with longitudinal observation of telomere length remains unclear. We evaluated the association of green tea, coffee, and soft drink consumption with 6-year changes in leukocyte telomere length (LTL). The study included 1952 participants who provided whole blood samples for LTL assays during the baseline (year 2011–2012) and follow-up (year 2017–2018) periods and reported baseline information on consumption of green tea, coffee, and soft drinks. Robust regression analysis was used to analyze the association adjusted for potential confounding variables. In the results, an inverse association between green tea consumption and LTL changes from baseline, which indicate telomere shortening, was found; regression coefficient [95% confidence interval] was − 0.097 [− 0.164, − 0.029] for participants who daily consumed at least 1 cup of green tea compared with non-consumers (p value = 0.006). This association was stronger among women (versus men) and younger participants aged 50–64 years (versus older). However, a positive association between soft drink consumption and LTL shortening was observed among women (p value < 0.05). Coffee consumption was not associated with LTL changes. These findings suggested that green tea consumption may be protective against telomere shortening reflecting biological aging whereas coffee and soft drink consumption may not

Association of blood pressure measurements in sitting, supine, and standing positions with the 10-year risk of mortality in Korean adults

OBJECTIVES This prospective cohort study investigated the association between blood pressure (BP) as measured in different body postures and all-cause and cardiovascular (CV) mortality risk. METHODS This population-based investigation included 8,901 Korean adults in 2001 and 2002. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured sequentially in the sitting, supine, and standing positions and classified into 4 categories: (1) normal, SBP <120 mmHg and DBP <80 mmHg; (2) high normal/prehypertension, SBP 120-129 mmHg and DBP <80 mmHg/SBP 130-139 mmHg or DBP 80-89 mmHg; (3) grade 1 hypertension (HTN), with SBP 140-159 mmHg or DBP 90-99 mmHg; and (4) grade 2 HTN, SBP ≥160 mmHg or DBP ≥100 mmHg. The date and cause of individual deaths were confirmed in the death record data compiled until 2013. Data were analyzed using Cox proportional hazard regression. RESULTS Significant associations were found between the BP categories and all-cause mortality, but only when BPs were measured in the supine position. The multivariate hazard ratios (95% confidence intervals, [CIs]) were 1.36 (95% CI, 1.06 to 1.75) and 1.59 (95% CI, 1.06 to 2.39) for grade 1 HTN and grade 2 HTN, respectively, compared with the normal category. The associations between the BP categories and CV mortality were significant regardless of body posture among participants ≥65 years, whereas they were significant for supine BP measurements only in those <65 years. CONCLUSIONS BP measured in the supine position predicted all-cause mortality and CV mortality better than BP measured in other postures