Newborn DNA methylation and asthma acquisition across adolescence and early adulthood

Abstract The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.

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Genome‐wide analysis of DNA methylation in relation to socioeconomic status during development and early adulthood

American Journal of Physical Anthropology ◽

10.1002/ajpa.23800 ◽

2019 ◽

Vol 169 (1) ◽

pp. 3-11 ◽

Cited By ~ 26

Author(s):

Thomas W. McDade ◽

Calen P. Ryan ◽

Meaghan J. Jones ◽

Morgan K. Hoke ◽

Judith Borja ◽

...

Keyword(s):

Dna Methylation ◽

Socioeconomic Status ◽

Early Adulthood ◽

Genome Wide Analysis ◽

Genome Wide

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DNA methylation at birth is associated with lung function development till age 26 years

European Respiratory Journal ◽

10.1183/13993003.03505-2020 ◽

2020 ◽

pp. 2003505

Author(s):

Nandini Mukherjee ◽

Ryan Arathimos ◽

Su Chen ◽

Parnian Kheirkhah Rahimabad ◽

Luhang Han ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Lung Function ◽

Early Adulthood ◽

Forced Expiratory Volume ◽

Parents And Children ◽

Forced Expiratory Flow ◽

Heel Prick ◽

F2 Generation ◽

Preventative Interventions

Little is known about whether DNA methylation (DNAm) of cytosine-phosphate-guanine (CpG) sites at birth predicts patterns of lung function development. We used heel prick DNAm from the F1-generation of Isle of Wight birth cohort (IOWBC-F1) for discovery of CpGs associated with lung function trajectories (Forced Expiratory Volume, Forced Vital Capacity, their ratio, and Forced Expiratory Flow at 25–75%) over the first 26 years, stratified by sex. We replicated the findings in the Avon Longitudinal Study of Parents and Children (ALSPAC) using cord blood DNAm.Epigenome-wide screening was applied to identify CpGs associated with lung function trajectories in 396 boys, and 390 girls of IOWBC-F1. Replication in ALSPAC focused on lung function at ages 8, 15 and 24 years. Statistically significantly replicated CpGs were investigated for consistency in direction of association between cohorts, stability of DNAm over time in IOWBC-F1, relevant biological processes, and for association with gene expression (n=161) in IOWBC F2-generation (IOWBC-F2).Differential DNAm of 8 CpGs on genes GLUL, MYCN, HLX, LHX1, COBL, COL18A1, STRA6, and WNT11 involved in developmental processes, were significantly associated with lung function in the same direction in IOWBC-F1 and ALSPAC, and showed stable patterns at birth, age 10 and 18 years between high and low lung function trajectories in IOWBC-F1. CpGs on LHX1 and COL18A1 were linked to gene expression in IOWBC-F2.In two large cohorts, novel DNAm at birth were associated with patterns of lung function in adolescence and early adulthood providing possible targets for preventative interventions against adverse pulmonary function development.

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Brain expressed FKBP5 delineates a therapeutic subtype of severe mental illness

10.1101/2021.01.27.428487 ◽

2021 ◽

Author(s):

Natalie Matosin ◽

Janine Arloth ◽

Silvia Martinelli ◽

Darina Czamara ◽

Malosree Maitra ◽

...

Keyword(s):

Dna Methylation ◽

Psychiatric Disorders ◽

Dorsolateral Prefrontal Cortex ◽

Large Scale ◽

Early Adulthood ◽

Pyramidal Cells ◽

Later Life ◽

Superficial Layer ◽

Treatment Development ◽

Dorsolateral Prefrontal

SUMMARYDeducing genes capable of classifying biologically-distinct psychiatric subtypes, and their targets for treatment, is a priority approach in psychiatry. FKBP5 is one such gene with strong evidence of utility to delineate a trans-diagnostic psychiatric subtype. Yet how brain-expressed FKBP5 is affected in psychiatric disorders in humans is not fully understood and critical for propelling FKBP5-targeting treatment development. We performed a large-scale postmortem study (n=895) of FKBP5 using dorsolateral prefrontal cortex samples derived from individuals with severe psychiatric disorders with a comprehensive battery of bulk/single-cell omics and histological analyses. We observed consistently heightened FKBP5 mRNA and protein in psychopathology, moderated by genotype and age, and accompanied by DNA methylation changes in key enhancers. These effects were most prominent in superficial-layer pyramidal cells. Heightened FKBP5 was also differentially associated with downstream pathways according to age, being specifically associated with synaptic transmission in early adulthood, and neuroinflammation and neurodegeneration in later life.

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Perinatal polychlorinated biphenyls and polychlorinated dibenzofurans exposure are associated with DNA methylation changes lasting to early adulthood: Findings from Yucheng second generation

Environmental Research ◽

10.1016/j.envres.2019.01.001 ◽

2019 ◽

Vol 170 ◽

pp. 481-486 ◽

Cited By ~ 5

Author(s):

Kang-Yi Su ◽

Ming-Chieh Li ◽

Nian-Wei Lee ◽

Bing-Ching Ho ◽

Chiou-Ling Cheng ◽

...

Keyword(s):

Dna Methylation ◽

Polychlorinated Biphenyls ◽

Second Generation ◽

Early Adulthood ◽

Polychlorinated Dibenzofurans

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DNA methylation in satellite repeats disorders

Essays in Biochemistry ◽

10.1042/ebc20190028 ◽

2019 ◽

Vol 63 (6) ◽

pp. 757-771 ◽

Cited By ~ 4

Author(s):

Claire Francastel ◽

Frédérique Magdinier

Keyword(s):

Dna Methylation ◽

Human Genome ◽

Repetitive Dna ◽

Dna Sequences ◽

Satellite Repeats ◽

Tremendous Progress ◽

Genes Encoding ◽

Dna Elements ◽

Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_pers-sig5-2019-0002 ◽

2019 ◽

Vol 4 (4) ◽

pp. 633-640 ◽

Cited By ~ 1

Author(s):

Canice E. Crerand ◽

Ari N. Rabkin

Keyword(s):

Cognitive Abilities ◽

Psychotic Disorders ◽

Developmental Stages ◽

Early Adulthood ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Psychosocial Risks ◽

Empirically Supported ◽

Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

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Inflammational Animal Models for Schizophrenia

Zeitschrift für Psychologie ◽

10.1027/2151-2604/a000216 ◽

2015 ◽

Vol 223 (3) ◽

pp. 157-164 ◽

Cited By ~ 1

Author(s):

Georg Juckel

Keyword(s):

Animal Model ◽

Animal Models ◽

Immune Activation ◽

Microglial Activation ◽

Treatment Options ◽

Early Adulthood ◽

Brain Regions ◽

Synaptic Connections ◽

Preventive Interventions ◽

Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

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