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Summary statistics for the article "Fathers’ preconception smoking and offspring DNA methylation: A two generation study'
Summary statistics for Fathers’ preconception smoking and offspring DNA methylation: A two generation study of Rhinessa Cohort to be published in Clinical Epigenetics</span
Summary statistics in support of the article 'Father’s adolescent body silhouette is associated with offspring asthma, lung function and BMI through DNA methylation '
The summary statistics for 13 Epigenome Wide Association studies (EWAS) for Father body Silhouette and DNA methylation of RHINESSA Offsprings
1. FBS-8_ Father body silhouette at age 8 years.xlsx
2. FBS-V_ Father body silhouette at voice break.xlsx
3. FBS-Vm_ Father body silhouette at voice break in male.xlsx
4. FBS-Vf_ Father body silhouette at voice break in female.xlsx
5. FBS-30_ Father body silhouette at age 30 years.xlsx
6. FBS-V8c_ Father body silhouette change between voice break and age 8.xlsx
7. FBS-V8gr_Father body silhouette gain or reduced between age 8 and voice break.xlsx
8. FBS-V8rs_ Father body silhouette retain or swap between age 8 and voice break.xlsx
9. FBS-V30c_ Father body silhouette change between voice break and age 30.xlsx
10. FBS-V30gr_Father body silhouette gain or reduced between voice break and age 30.xlsx
11. FBS-V30rs_ Father body silhouette retain or swap between voice break and age 30.xlsx
12. Offspring current BMI.xlsx
13. Offspring Current body Silhouette.xlsx
Supplementary data
Data 1A EWAS dmCpGs.xlsx Data 1B EWAS dmCpGs Mvalue and beta compared_VB.xlsx
Data 2 DMR.xlsx
Data 3 TF.xlsx
Data 4 eQTL.xlsx
Data 5 methylRR.xlsx
Data 6 Gene ontology terms.xlsx
Data 7 KEGG Wikipathway.xls
Data 8 Overlab GWAS Catalague.xlsx
Data 9 Overlap EWASatlas.xlsx
Data 10A meQTL goDMC.xlsx
Data 10B meQTL EPIC_Database.xlsx
Data 11 imprinted gene and metastable epialleles.xlsx
Data 12A BMI.xlsx
Data 12B Asthma.xlsx
Data 12C Lung function.xlsx
Data 13 offspring BMI and body silhouette.xlsx
Data 14 Obesity related dmCpG Open Targets and DisGeNET.xlsx
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A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation
Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted
Immune transcriptomic differences in paediatric patients with SARS-CoV-2 compared to other lower respiratory tract infections
The clinical severity of SARS-CoV-2 infection in children varies, with asymptomatic or mild illness predominating and a minority developing severe disease. Understanding the immunological responses that underlie severity of disease may guide future development of preventive or therapeutic interventions. This study compared whole blood transcriptomes of healthy children (N=127), children with mild/asymptomatic SARS-CoV-2 infection (N=71) and children hospitalised with severe SARS-COV-2 (N=41), lower respiratory tract illness (LRTI) or LRTI due to Respiratory Syncytial Virus (RSV-LRTI) (N=47) or Pulmonary Tuberculosis (PTB) (N=47). We identified >5000 differentially expressed genes including: OLFM4, IFI27, CBX7, IGF2BP3, OTOF for severe SARS-CoV-2; IFI27, OTOF, SIGLEC1, IFI44L and USP18 for RSV-LRTI, and MMP8, LTF, IGF2BP3, GPR84, CD177, C1QC and DEFA4 for PTB, at false discovery rate (FDR) <0.05. Pathway analysis identified enrichment for neutrophil degranulation, interferon gamma signalling, overexpression of ribosomal proteins and depletion of immune response in severe SARS-CoV-2 compared to healthy (SAR-COV-2 uninfected) children. Weighted Gene Co-expression Network Analysis ( WGCNA ) identified 10 correlated gene modules shared between LRTI showing similar underlying response mechanisms. Cellular decomposition analysis identified the depletion of 22 cell types in severe SARS-CoV-2, 16 for RSV-LRTI and 21 for PTB compared to healthy SARS-CoV-2 uninfected control children. We identified 82 genes important for discriminating asymptomatic/mild from severe SARS-CoV-2 including CBX7, TRAF1, ZNF324 and CASS4 ; 93 healthy from severe SARS-CoV-2 including RORC, CBX7, NR3C2, MID2 and ADAMTS2 ; 110 genes for RSV-LRTI and 95 for PTB children which can be used for future therapeutic targets. </p
Development of Models for the Action of Novel Anti-apoptotic Proteins using Gene Regulation, Pathway Analysis and Protein Structure Prediction
Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity
Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (β = 0.031, 95% CI 0.001-0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.</p
DNA methylation signatures in cord blood associated with birthweight are enriched for dmCpGs previously associated with maternal hypertension or pre-eclampsia, smoking and folic acid intake
Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women’s Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10−8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: −241, −149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10−255), maternal smoking (7.71%, p = 1.50 x 10−57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCD
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Ascaris exposure and its association with lung function, asthma, and DNA methylation in Northern Europe
BackgroundAscaris infections, with a worldwide prevalence above 10%, can cause respiratory pathology. However, long-term effects on lung function in humans are largely unknown.ObjectiveWe investigated the associations of Ascaris exposure with lung function, asthma, and DNA methylation.MethodsSerum Ascaris IgG antibodies were measured in 671 adults aged 18 to 47 years (46% women) from Aarhus, Bergen, and Tartu RHINESSA study centers. Seropositivity was defined as IgG above the 90th percentile. Linear and logistic regressions were used to analyze Ascaris seropositivity as associated with lung function and asthma, adjusted for age, height, and smoking and clustered by center. DNA methylation in blood was profiled by a commercial methylation assay.ResultsAscaris seropositivity was associated with lower FEV1 (−247 mL; 95% CI, −460, −34) and higher odds for asthma (adjusted odds ratio, 5.84; 95% CI, 1.67, 20.37) among men but not women, also after further adjusting for house dust mite sensitivity, consistent across study centers. At a genome-wide level, Ascaris exposure was associated with 23 differentially methylated sites in men and 3 in women. We identified hypermethylation of the MYBPC1 gene, which can regulate airway muscle contraction. We also identified genes linked to asthma pathogenesis such as CRHR1 and GRK1, as well as a differentially methylated region in the PRSS22 gene linked to nematode infection.ConclusionAscaris exposure was associated with substantially lower lung function and increased asthma risk among men. Seropositive participants had sex-specific differences in DNA methylation compared to the unexposed, thus suggesting that exposure may lead to sex-specific epigenetic changes associated with lung pathology
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