Simon Kebede Merid

• Bioinformatician at Karolinska Institutet

Background Protein quantitative trait loci (pQTLs) remain underexplored in asthma but might provide valuable insights into the underlying molecular mechanisms. This study aimed to investigate associations between genetic variation and inflammation‐related plasma proteins and to assess differences in the levels of genetically determined proteins in...

Background Few studies showed associations of childhood allergic diseases with epigenetic aging using traditional clocks trained mainly on adults. Tracking DNA methylation variation early in life has suggested poor performance of these clocks in children. Therefore, we aim to elucidate the association between allergic diseases and epigenetic age us...

Background DNA methylation (DNAm) is a developmentally dynamic epigenetic process; yet, most epigenome-wide association studies (EWAS) have examined DNAm at only one timepoint or without systematic comparisons between timepoints. Thus, it is unclear whether DNAm alterations during certain developmental periods are more informative than others for h...

Background Asthma exacerbations (AEs) represent the major contributor to the global asthma burden. Although genetic and environmental factors have been associated with AEs, the role of epigenetics remains uncovered. Objective This study aimed to identify whole blood DNA methylation (DNAm) markers associated with AEs in Europeans. Methods DNAm was...

The recent COVID-19 pandemic has posed major health challenges. To expand our molecular understanding beyond those seeking medical care, we conducted a cross-sectional survey targeting random residents from Sweden’s two largest cities. Two thousand participants were invited during 2021 to self-sample dried blood spots (DBS) and provide health infor...

Background In COPD, the balance between matrix metalloproteinases (MMPs) and their natural inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] is shifted towards excessive degradation, reflected in bronchoalveolar lavage (BAL) as increased MMP concentrations. Because of their critical role in lung homeostasis, MMP activity is tightly regul...

Background Numerous studies have investigated links between body mass index (BMI) trajectories and cardiovascular risk, yet discrepancies in BMI measurement duration and timing of the cardiovascular-related outcome evaluation have led to inconsistent findings. Methods We included participants from the Swedish birth cohort (BAMSE) and applied laten...

Background Limited studies have investigated the influence of body mass index (BMI) trajectories on lung function covering the entire growth period. Methods We conducted a prospective study utilizing data from the Swedish BAMSE birth cohort. Latent class mixture modelling was employed to examine the diversity in BMI z-scores from birth to 24 years...

Background Asthma is associated with impaired lung function; however, it is uncertain if a lower childhood lung function is associated with asthma onset and persistence during adolescence. Aims To investigate the association between childhood lung function and onset and persistence of asthma during adolescence. Methods In the population-based BAM...

Background Noninvasive biomarkers for diagnosing and monitoring eosinophilic esophagitis (EoE) are currently lacking. This study evaluates 20 biomarkers in serum and saliva, aiming to assess their diagnostic potential in pediatric EoE patients and healthy individuals. Methods Blood and saliva from children undergoing upper endoscopy were analyzed...

Background Chronic obstructive pulmonary disease (COPD) is caused by interactions between many factors across the life course, including genetics. A proportion of COPD may be due to reduced lung growth in childhood. We hypothesized that a polygenic risk score (PRS) for COPD is associated with lower lung function already in childhood and up to adult...

Rationale The benefits of improved air quality on asthma remain understudied. Objectives Our aim was to investigate associations of changes in ambient air pollution with incident asthma from school age until young adulthood in an area with mostly low air pollution levels. Methods Participants in the BAMSE (Swedish abbreviation for Children, Aller...

Background & aim: Clinical trials supplementing the long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) to preterm infants have shown positive effects on inflammation-related morbidities, but the molecular mechanisms underlying these effects are not fully elucidated. This study aimed to determine as...

DNA methylation (DNAm) is a developmentally dynamic epigenetic process, yet we still know little about how epigenetic effects on health outcomes vary over time; whether DNAm alterations during certain periods of development are more informative than others; and whether epigenetic timing effects differ by outcome. To address these questions, we appl...

Background Moderate-to-late preterm birth (32- <37 weeks of gestation) has been associated with impaired lung function in adolescence, but data in adulthood and physiologic phenotyping beyond spirometry are scarce. We aimed to investigate lung function development from adolescence into young adulthood and to provide physiologic phenotyping in indiv...

Background: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. Methods: We carried...

Flash Talk

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (n = 2,420) or c...

Background: The beneficial effect of improving air quality on lung function development remains understudied. We assessed associations of changes in ambient air pollution levels with lung function growth from childhood until young adulthood in a Swedish cohort study. Methods: In the prospective birth cohort BAMSE (Children, Allergy, Environment, S...

Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Pre-bronchodilator FEV1 z-scores determined at age 8, 16 and 24 years in the Swedish population-based birth cohort BAMS...

Background DNA methylation (DNAm) is considered a plausible pathway through which genetic and environmental factors may influence the development of allergies. However, causality has yet to be determined as it is unknown whether DNAm is rather a cause or consequence of allergic sensitization. Here, we investigated the direction of the observed asso...

Rationale: The identification of novel molecules associated with asthma may provide insights into mechanisms of disease and their potential clinical implications. Objectives: To conduct a screening of circulating proteins in childhood asthma and to study proteins emerged from human studies in a mouse model of asthma. Methods: We included 2,264...

DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on bronchoalveolar lavage (BAL) cells. Bronchoscopies were performed in 18 COPD subjects and 15 controls (ex- and...

Peanut allergy is a common food allergy and the main cause of anaphylaxis among children1. In recent years, oral immunotherapy has emerged as a promising treatment for children with different IgE‐mediated food allergies, although safety issues must be considered2. The main aim of immunotherapy is to induce tolerance or desensitization to an allerge...

A digital multidisciplinary European expert meeting took place on the 9 July 2020 to identify the unmet needs of paediatric severe asthma patients, and set the priorities for clinical and research activities ahead https://bit.ly/3CeLBHB.

Aim We aimed to assess prevalence of IgG antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and factors associated with seropositivity in a large cohort of healthcare workers (HCWs). Methods From 11 May until 11 June 2020, 3981 HCWs at a large Swedish emergency care hospital provided serum samples and questionnaire data. Pr...

Obesity-related inflammation is associated with cardiovascular, metabolic, and pulmonary diseases. The aim of this study was to demonstrate associations between adiposity measurements and levels of inflammation-related plasma proteins in a population of young adults. Subjects from a population-based birth cohort with a mean age of 22.5 years were i...

Aim: We aimed to assess the risk for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in a large cohort of healthcare workers (HCWs). Methods: From May 11 until June 11, 2020, 3,981 HCWs at a large Swedish Emergency Care hospital provided serum samples and questionnaire data. Exposure was measured by assaying IgG antibodies to...

Purpose of review: Asthma is a common disease worldwide, however, its pathogenesis has not been fully elucidated. Emerging evidence suggests that epigenetic modifications may play a role in the development and natural history of asthma. The aim of this review is to highlight recent progress in research on epigenetic mechanisms in asthma. Recent f...

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle...

Air pollution has been associated with adverse health effects across the life-course. Although underlying mechanisms are unclear, several studies suggested pollutant-induced changes in transcriptomic profiles. In this meta-analysis of transcriptome-wide association studies of 656 children and adolescents from three European cohorts participating in...

Background: Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related...

Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's...

There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregn...

Background Response to inhaled corticosteroids is highly variable, and the association between DNA methylation and treatment response is not known. Objective To examine the association between peripheral blood DNA methylation and inhaled corticosteroid response in children with persistent asthma. Methods Epigenome‐wide DNA methylation was analyze...

Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula:...

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweigh...

Early allergic sensitisation (atopy) is the first step in the development of allergic diseases such as atopic asthma later in life. Genes and pathways associated with atopy and atopic asthma in children and adolescents have not been well characterised. A transcriptome-wide association study of atopy and atopic asthma in white blood cells or whole b...

Background The presence of allergic sensitization has a major influence on the development and course of common childhood conditions such as asthma and rhinitis. The etiology of allergic sensitization is poorly understood, and its underlying biological mechanisms are not well established. Several studies showed that DNA methylation (DNAm) at some C...

Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood...

Our hypothesis was that children with mutations in genes coding for glutathione S-transferases (GST) have worse asthma outcomes compared with children with active type genotype. Data were collected in five populations. The rs1695 single nucleotide polymorphism (GSTP1) was determined in all cohorts (3692 children) and GSTM1 and GSTT1 null genotype w...

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of...

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweigh...

Silver-Russell syndrome (SRS) is a growth retardation syndrome in which loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy for chromosome 7 [UPD(7)mat] explain 20–60% and 10% of the syndrome, respectively. To search for a molecular cause for the remaining SRS cases, and to find a possible common epigenetic change, w...

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Epigenetic modifications such as DNA methylation could contribute, but data are scarce. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over...

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methy...

Background: Long-term exposure to ambient air pollution can lead to adverse health effects in children; however, underlying biological mechanisms are not fully understood. Objectives: We evaluated the effect of air pollution exposure during different time periods on mRNA expression as well as circulating levels of inflammatory cytokines in child...

Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107)Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) in Neuropeptide S (NPS) encodes a Val(6)Leu substitution on the mature peptide that results in reduced bioactivity. We s...

Predicted changes in transcription factor binding sites encoded by the SNPs implicated in the epistasis between NPS and NPSR1 as determined by the Genomatix Software Suite. (XLS)

Interactions between NPS and NPSR1 on the risk of asthma under the multiplicative model. (DOCX)

Primers used for qPCR analysis in the human cell lines and mice experiments. (DOCX)