DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication

Lower fine motor performance in childhood has been associated with poorer cognitive development and neurodevelopmental conditions such as autism spectrum disorder, yet, biological underpinnings remain unclear. DNA methylation (DNAm), an essential process for healthy neurodevelopment, is a key molecular system of interest. In this study, we conducted the first epigenome-wide association study of neonatal DNAm with childhood fine motor ability and further examined the replicability of epigenetic markers in an independent cohort. The discovery study was embedded in Generation R, a large population-based prospective cohort, including a subsample of 924 ~ 1026 European-ancestry singletons with available data on DNAm in cord blood and fine motor ability at a mean (SD) age of 9.8 (0.4) years. Fine motor ability was measured using a finger-tapping test (3 subtests including left-, right-hand and bimanual), one of the most frequently used neuropsychological instruments of fine motor function. The replication study comprised 326 children with a mean (SD) age of 6.8 (0.4) years from an independent cohort, the INfancia Medio Ambiente (INMA) study. Four CpG sites at birth were prospectively associated with childhood fine motor ability after genome-wide correction. Of these, one CpG (cg07783800 in GNG4) was replicated in INMA, showing that lower levels of methylation at this site were associated with lower fine motor performance in both cohorts. GNG4 is highly expressed in the brain and has been implicated in cognitive decline. Our findings support a prospective, reproducible association between DNAm at birth and fine motor ability in childhood, pointing to GNG4 methylation at birth as a potential biomarker of fine motor ability

DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication

Lower fine motor performance in childhood has been associated with poorer cognitive development and neurodevelopmental conditions such as autism spectrum disorder, yet, biological underpinnings remain unclear. DNA methylation (DNAm), an essential process for healthy neurodevelopment, is a key molecular system of interest. In this study, we conducted the first epigenome-wide association study of neonatal DNAm with childhood fine motor ability and further examined the replicability of epigenetic markers in an independent cohort. The discovery study was embedded in Generation R, a large population-based prospective cohort, including a subsample of 924 ~ 1026 European-ancestry singletons with available data on DNAm in cord blood and fine motor ability at a mean (SD) age of 9.8 (0.4) years. Fine motor ability was measured using a finger-tapping test (3 subtests including left-, right-hand and bimanual), one of the most frequently used neuropsychological instruments of fine motor function. The replication study comprised 326 children with a mean (SD) age of 6.8 (0.4) years from an independent cohort, the INfancia Medio Ambiente (INMA) study. Four CpG sites at birth were prospectively associated with childhood fine motor ability after genome-wide correction. Of these, one CpG (cg07783800 in GNG4) was replicated in INMA, showing that lower levels of methylation at this site were associated with lower fine motor performance in both cohorts. GNG4 is highly expressed in the brain and has been implicated in cognitive decline. Our findings support a prospective, reproducible association between DNAm at birth and fine motor ability in childhood, pointing to GNG4 methylation at birth as a potential biomarker of fine motor ability

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Background Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Abstract Background Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases

Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases

Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement