Children’s internalizing behavior development is heterogeneously associated with the pace of epigenetic aging

Carlos, Juan; Holuka, Cyrielle; Menta, Giorgia; Turner, Jonathan D.; Vögele, Claus; D’Ambrosio, Conchita

doi:10.1016/j.biopsycho.2022.108463

Cited by 4 publications

(3 citation statements)

References 54 publications

(59 reference statements)

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“…This assay covers over 450,000 CpG sites across the human genome, including 16 CpG sites in SLC6A4 and 27 CpG sites in HTR2A , which were of interest in our study. Procedures for blood sample collection and storage, DNA extraction, DNA methylation analysis, and details of data pre-processing, normalization, and correction for batch effects and cellular heterogeneity have been described elsewhere [ 78 , 79 ]. Statistical analyses were performed using beta (β) value, the ratio between the intensity of the methylated probe and the total intensity, where 0 represents an unmethylated cytosine and 1 represents a fully methylated cytosine.…”

Section: Methodsmentioning

confidence: 99%

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Bečeheli,

Horvatiček,

Perić

et al. 2024

Clin Epigenet

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Background Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database. Results None of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites. Conclusions Methylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

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Section: Methodsmentioning

confidence: 99%

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Bečeheli,

Horvatiček,

Perić

et al. 2024

Clin Epigenet

Self Cite

View full text Add to dashboard Cite

show abstract

“…CpG sites across the human genome, including 16 CpG sites in SLC6A4 and 27 CpG sites in HTR2A, which were of interest in our study. Procedures for blood sample collection and storage, DNA extraction, DNA methylation analysis, and details of data pre-processing, normalization, and correction for batch effects and cellular heterogeneity have been described elsewhere[78,79]. The degree of methylation is reported as beta (β) value, the ratio between the intensity of the methylated probe and the total intensity, where 0 represents an unmethylated cytosine and 1 represents a fully methylated cytosine.ARIES is a sub-study of the Avon Longitudinal Study of Parents and Children (ALSPAC)[78].…”

mentioning

confidence: 99%

Methylation of serotonin regulating genes in cord blood cells: modulation by maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Bečeheli,

Horvatiček,

Perić

et al. 2023

Preprint

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Background Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters – pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) vs. normal glucose tolerance (NGT) – and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database. Results None of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site − 1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites. Conclusions Methylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

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“…Among these are the Strengths and Difficulties Questionnaires (SDQ) 348 and the Child Behaviour Checklist (CBCL) 349 . However, a NonCog PGS based on our GWAS was reported to not be associated with measures of internalizing behaviour in ALSPAC 350,351 , measured with SDQ. In adulthood, NonCog PGS was not associated with neuroticism in NTR, Texas Twins and WLS cohorts (Chapter 2)…”

Section: Can We Further Separate Noncognitive Skills From Cognitive S...mentioning

confidence: 63%

Intergenerational transmission of education and mental health

Demange

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Education and mental health shape individuals’ wellbeing and their opportunities in life. Understanding the relationship between these two domains and their intergenerational transmission is valuable for researchers, policy makers, and society as a whole. With this doctoral dissertation, I tried to further our understanding of the causes of individual differences in educational outcomes, their relationship with mental health, and their co-intergenerational transmission. In my research I worked with observational data in large samples, triangulating across several genetically-informed designs to study genetic and environmental transmissions.

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Children’s internalizing behavior development is heterogeneously associated with the pace of epigenetic aging

Cited by 4 publications

References 54 publications

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Methylation of serotonin regulating genes in cord blood cells: modulation by maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

Intergenerational transmission of education and mental health

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