Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers

Background The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. Objective We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. Methods We used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell–derived IL-1β levels were measured by means of ELISA. Results Neonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma-associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1β, an innate inflammatory mediator. Conclusions The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory

Relationship between spatial ability, visuospatial working memory and self-assessed spatial orientation ability: a study in older adults

This paper describes some novel spatial tasks and questionnaires designed to assess spatial and orientation abilities. The new tasks and questionnaires were administered to a sample of 90 older adults (41 males, age range 57–90), along with some other tests of spatial ability (Minnesota Paper Form Board, Mental Rotations Test, and Embedded Figures Test) and tests of visuospatial working memory (Corsi’s Block Test and Visual Pattern Test). The internal reliability of the new tasks and questionnaires was analyzed, as well as their relationship with the spatial and working memory tests. The results showed that the new spatial tasks are reliable, correlate with working memory and spatial ability tests and, compared with the latters, show stronger correlations with the self-report questionnaires referring to orientation abilities. A model was also tested (with reference to Allen et al. in Intelligence 22:327–355, 1996) in which the new tasks were assumed to relate to spatial ability and predict orientation abilities as assessed by the self-report measures