scholarly journals Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills

2020 ◽  
Author(s):  
Doretta Caramaschi ◽  
Alexander Neumann ◽  
Andres Cardenas ◽  
Gwen Tindula ◽  
Silvia Alemany ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Cognitive Abilities ◽  
Cognitive Skills ◽  
Strong Predictor ◽  
Meta Analysis ◽  
Later Life ◽  
Life Outcomes ◽  
Cognitive Domains ◽  
Wide Range

ABSTRACTCognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts (N=2196-3798) within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall, verbal and non-verbal cognitive scores. The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that cord blood DNA methylation at single CpGs can predict cognitive skills and further studies are needed to confirm regional differences.

scholarly journals Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Simon Kebede Merid ◽  
Alexei Novoloaca ◽  
Gemma C. Sharp ◽  
Leanne K. Küpers ◽  
Alvin T. Kho ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Health Effects ◽  
Gestational Age ◽  
Meta Analysis ◽  
Fetal Brain ◽  
Later Life ◽  
Childhood And Adolescence ◽  
Pathway Analyses

Abstract 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 HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P < 1.06 × 10− 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

scholarly journals Polygenic Scores for Cognitive Abilities and their Association with Different Aspects of General Intelligence – a Deep Phenotyping Approach

2020 ◽  
Author(s):  
Erhan Genç ◽  
Caroline Schlüter ◽  
Christoph Fraenz ◽  
Larissa Arning ◽  
Huu Phuc Nguyen ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Large Scale ◽  
Short Term Memory ◽  
Life Outcomes ◽  
Short Term ◽  
Polygenic Scores ◽  
Wide Range ◽  
Dna Variants ◽  
Trait Prediction ◽  
Deep Phenotyping

AbstractIntelligence is a highly polygenic trait and GWAS have identified thousands of DNA variants contributing with small effects. Polygenic scores (PGS) can aggregate those effects for trait prediction in independent samples. As large-scale light-phenotyping GWAS operationalized intelligence as performance in rather superficial tests, the question arises which intelligence facets are actually captured. We used deep-phenotyping to investigate the molecular determinantes of individual differences in cognitive ability. We therefore studied the association between PGS of educational attainment (EA-PGS) and intelligence (IQ-PGS) with a wide range of intelligence facets in a sample of 320 healthy adults. EA-PGS and IQ-PGS had the highest incremental R2s for general (3.25%; 1.78%), verbal (2.55%; 2.39%) and numerical intelligence (2.79%; 1.54%) and the weakest for non-verbal intelligence (0.50%; 0.19%) and short-term memory (0.34%; 0.22%). These results indicate that PGS derived from light-phenotyping GWAS do not reflect different facets of intelligence equally well, and thus should not be interpreted as genetic indicators of intelligence per se. The findings refine our understanding of how PGS are related to other traits or life outcomes.

scholarly journals Genetic Underpinnings of Increased BMI and Its Association With Late Midlife Cognitive Abilities

2020 ◽  
Vol 6 ◽  
pp. 233372142092526
Author(s):  
Hong Xian ◽  
Brian Boutwell ◽  
Chandra A. Reynolds ◽  
Daphne Lew ◽  
Mark Logue ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Cognitive Abilities ◽  
Later Life ◽  
Risk Scores ◽  
Linear Regression Models ◽  
Cognitive Domains ◽  
Memory Processing ◽  
Visual Spatial ◽  
Bmi Trajectories ◽  
Multilevel Linear Regression

Objectives: First, we test for differences in various cognitive abilities across trajectories of body mass index (BMI) over the later life course. Second, we examine whether genetic risk factors for unhealthy BMIs—assessed via polygenic risk scores (PRS)—predict cognitive abilities in late-life. Methods: The study used a longitudinal sample of Vietnam veteran males to explore the associations between BMI trajectories, measured across four time points, and later cognitive abilities. The sample of 977 individuals was drawn from the Vietnam Era Twin Study of Aging. Cognitive abilities evaluated included executive function, abstract reasoning, episodic memory, processing speed, verbal fluency, and visual spatial ability. Multilevel linear regression models were used to estimate the associations between BMI trajectories and cognitive abilities. Then, BMI PRS was added to the models to evaluate polygenic associations with cognitive abilities. Results: There were no significant differences in cognitive ability between any of the BMI trajectory groups. There was a significant inverse relationship between BMI-PRS and several cognitive ability measures. Discussion: While no associations emerged for BMI trajectories and cognitive abilities at the phenotypic levels, BMI PRS measures did correlate with key cognitive domains. Our results suggest possible polygenic linkages cutting across key components of the central and peripheral nervous system.

Visual Literacy

2017 ◽  
Author(s):  
Frank Serafini
Keyword(s):  
Social Sciences ◽  
Cognitive Abilities ◽  
Cognitive Skills ◽  
Social Practice ◽  
Visual Literacy ◽  
Social Contexts ◽  
Visual Images ◽  
Design Elements ◽  
The Social ◽  
Wide Range

Visual literacy was originally defined as a set of visual competencies or cognitive skills and strategies one needs to make sense of visual images. These visual competencies were seen as universal cognitive abilities that were used for understanding visual images regardless of the contexts of production, reception, and dissemination. More contemporary definitions suggest visual literacy is a contextualized, social practice as much as an individualized, cognitively based set of competencies. Visual literacy is more aptly defined as a process of generating meanings in transaction with multimodal ensembles that include written text, visual images, and design elements from a variety of perspectives to meet the requirements of particular social contexts. Theories of visual literacy and associated research and pedagogy draw from a wide range of disciplines including art history, semiotics, media and cultural studies, communication studies, visual ethnography and anthropology, social semiotics, new literacies studies, cognitive psychology, and critical theory. Understanding the various theories, research methodologies, and pedagogical approaches to visual literacy requires an investigation into how the various paradigm shifts that have occurred in the social sciences have affected this field of study. Cognitive, linguistic, sociocultural, multimodal, and postmodern “turns” in the social sciences each bring different theories, perspectives, and approaches to the field of visual literacy. Visual literacy now incorporates sociocultural, semiotic, critical, and multimodal perspectives to understand the meaning potential of the visual and verbal ensembles encountered in social environments.

Neurocognitive impairment in deficit and non-deficit schizophrenia: a meta-analysis

2017 ◽  
Vol 47 (14) ◽  
pp. 2401-2413 ◽  
Author(s):  
E. Bora ◽  
B. Binnur Akdede ◽  
K. Alptekin
Keyword(s):  
Cognitive Abilities ◽  
Meta Analysis ◽  
Healthy Controls ◽  
Cognitive Domains ◽  
Deficit Syndrome ◽  
Deficit Schizophrenia ◽  
Analytic Review ◽  
Severe Impairment ◽  
Neurocognitive Profiles ◽  
The Relationship

BackgroundMost studies suggested that patients with deficit schizophrenia have more severe impairment compared with patients with non-deficit schizophrenia. However, it is not clear whether deficit and non-deficit schizophrenia are associated with differential neurocognitive profiles.MethodsThe aim of this meta-analytic review was to compare cognitive performances of deficit and non-deficit patients with each other and with healthy controls. In the current meta-analysis, differences in cognitive abilities between 897 deficit and 1636 non-deficit patients with schizophrenia were examined. Cognitive performances of 899 healthy controls were also compared with 350 patients with deficit and 592 non-deficit schizophrenia.ResultsBoth deficit (d= 1.04–1.53) and non-deficit (d= 0.68–1.19) schizophrenia were associated with significant deficits in all cognitive domains. Deficit patients underperformed non-deficit patients in all cognitive domains (d= 0.24–0.84) and individual tasks (d= 0.39–0.93). The relationship between deficit syndrome and impairment in olfaction, social cognition, verbal fluency, and speed-based cognitive tasks were relatively stronger.ConclusionsOur findings suggest that there is consistent evidence for a significant relationship between deficit syndrome and more severe cognitive impairment in schizophrenia.

Sport als Prävention von Demenz und ­funktionellem Verlust im Alter

2014 ◽  
Vol 62 (4) ◽  
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Cognitive Abilities ◽  
Lifestyle Changes ◽  
Cognitive Domains ◽  
Dementia Prevalence ◽  
Positive Effects ◽  
Preventative Measures ◽  
Wide Range ◽  
Study Designs

As a consequence of the demographically related increase of dementia prevalence, modifiable risk factors are gaining in importance as possible preventative measures. Medical treatment cannot yet heal dementia. The effects of vascular risk factors as well as behaviour and lifestyle changes on cognitive decline are the subject of a wide range of current literature. The role of physical activity has proved to be especially beneficial. Multiple studies with different study designs describe direct or indirect positive effects of physical activity on cognitive abilities. The positive effects of physical activity are particularly notable in cognitive domains such as attention or executive functions, which are often impaired in dementia. However, ideal training sessions in terms of type, duration and intensity are currently unknown.

scholarly journals DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins

2015 ◽  
Vol 18 (6) ◽  
pp. 635-646 ◽  
Author(s):  
Pei-Chien Tsai ◽  
Jenny Van Dongen ◽  
Qihua Tan ◽  
Gonneke Willemsen ◽  
Lene Christiansen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Random Effects ◽  
Meta Analysis ◽  
Monozygotic Twins ◽  
Positive Association ◽  
Later Life ◽  
Significant Positive Association ◽  
Association Analyses ◽  
A Genome

Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10−8), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.

scholarly journals Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys

2014 ◽  
Vol 5 (4) ◽  
pp. 288-298 ◽  
Author(s):  
K. Broberg ◽  
S. Ahmed ◽  
K. Engström ◽  
M. B. Hossain ◽  
S. Jurkovic Mlakar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
De Novo ◽  
Arsenic Exposure ◽  
Later Life ◽  
Linear Regression Models ◽  
Early Gestation ◽  
Cpg Sites ◽  
Genome Wide

Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov–Smirnov test, P-value<10–15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (rS-values>−0.62), but in girls only 207 (41%) showed inverse correlation (rS-values>−0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.

scholarly journals DNA methylation signatures of aggression and closely related constructs: A meta-analysis of epigenome-wide studies across the lifespan

2020 ◽  
Author(s):  
Jenny van Dongen ◽  
Fiona A. Hagenbeek ◽  
Matthew Suderman ◽  
Peter Roetman ◽  
Karen Sugden ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Aggressive Behavior ◽  
Peripheral Blood ◽  
Association Studies ◽  
Meta Analysis ◽  
Risk Tolerance ◽  
Blood Samples ◽  
Chemical Exposures ◽  
Starting Point

AbstractDNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N=15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha=1.2×10−7; Bonferroni correction). In cord blood samples of 2,425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r=0.74, p=0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripherl blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range=3-82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

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