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Article ; Online: Developmental epigenomic effects of maternal financial problems.

Holuka, Cyrielle / Menta, Giorgia / Caro, Juan Carlos / Vögele, Claus / D'Ambrosio, Conchita / Turner, Jonathan D

2024 , Page(s) 1–14

Abstract: Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in ...

Abstract	Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in epigenetic markers that are retained for many years.We investigated the effect of maternal major financial problems (MFP) and material deprivation (MD) on their children's epigenome in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Epigenetic aging, measured with epigenetic clocks, was weakly accelerated with increased MFP. In subsequent EWAS, MFP, and MD showed strong, independent programing effects on children's genomes. MFP in the period from birth to age seven was associated with genome-wide epigenetic modifications on children's genome visible at age 7 and partially remaining at age 15.These results support the hypothesis that physiological processes at least partially explain associations between early-life adversity and health problems later in life. Both maternal stressors (MFP/MD) had similar effects on biological pathways, providing preliminary evidence for the mechanisms underlying the effects of low socioeconomic status in early life and disease outcomes later in life. Understanding these associations is essential to explain disease susceptibility, overall life trajectories and the transition from health to disease.
Language	English
Publishing date	2024-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	1036173-x
ISSN	1469-2198 ; 0954-5794
ISSN (online)	1469-2198
ISSN	0954-5794
DOI	10.1017/S095457942400083X
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Article ; Online: Children's internalizing behavior development is heterogeneously associated with the pace of epigenetic aging.

Caro, Juan Carlos / Holuka, Cyrielle / Menta, Giorgia / Turner, Jonathan D / Vögele, Claus / D'Ambrosio, Conchita

Biological psychology

2022 Volume 176, Page(s) 108463

Abstract: Background: Internalizing behaviors are an indicator of children's psychological and emotional development, predicting future mental disorders. Recent studies have identified associations between DNA methylation (DNAm) and internalizing behaviors. This ... ...

Abstract	Background: Internalizing behaviors are an indicator of children's psychological and emotional development, predicting future mental disorders. Recent studies have identified associations between DNA methylation (DNAm) and internalizing behaviors. This prospective study aimed at exploring the associations between pace of biological aging and the developmental trajectories of internalizing behaviors. Methods: Participants were children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N = 974). Measures of DNA methylation were collected at birth, age 7 and ages 15-17. The pace of aging was estimated using the DunedinPoAm algorithm (PoAm). Internalizing behaviors reported by caregivers between ages 4 and 16 using the Strengths and Difficulties Questionnaire. To explore heterogeneity in the association between PoAm and internalizing behaviors we use Poisson quantile regression in cross-section heterogeneity and longitudinal latent class analysis over the childhood and adolescence. Results: Internalizing behavior trajectories were identified: low-risk, childhood limited, late onset and early onset (persistent). Accelerated aging at birth was negatively associated with internalizing behaviors in early childhood but positively correlated during adolescence. Higher PoAm at birth increased chance of low-risk profile, while decreasing likelihood of childhood limited trajectory. PoAm at age 15 was negatively associated with childhood limited profile and positively linked to late onset trajectories. Associations were larger at higher values of internalizing symptoms. Conclusions: The heterogeneity in the association between biological age acceleration and internalizing behaviors suggests a complex dynamic relationship, particularly in children with high or increased risk of adverse mental health outcomes.
MeSH term(s)	Adolescent ; Infant, Newborn ; Child ; Humans ; Child, Preschool ; Longitudinal Studies ; Prospective Studies ; Mental Disorders ; Aging/genetics ; Epigenesis, Genetic
Language	English
Publishing date	2022-11-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185105-6
ISSN	1873-6246 ; 0301-0511
ISSN (online)	1873-6246
ISSN	0301-0511
DOI	10.1016/j.biopsycho.2022.108463
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Zs.A 1544: Show issues

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Article ; Online: Mode of birth and DNA methylation at birth, in childhood, and in adolescence: Uncovering the relationship using ALSPAC data.

Jaramillo, Isabel / Bergunde, Luisa / Holuka, Cyrielle / Schuengel, Carlo / Štefulj, Jasminka / Steudte-Schmiedgen, Susann / Kaźmierczak, Maria / Menta, Giorgia / D'Ambrosio, Conchita / Lalor, Joan G / Turner, Jonathan D / Garthus-Niegel, Susan

Developmental psychology

2024

Abstract: Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal ... ...

Abstract	Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal birth compared with elective or emergency cesarean section) affects DNAm at birth, in childhood, and adolescence and whether these effects are modified by the postnatal care environment, specifically by breastfeeding and mother-infant bonding. Using data from 876 mother-infant dyads from the U.K. Avon Longitudinal Study of Parents and Children, we examined differentially methylated cytosine-phosphate-guanine dinucleotides and regions associated with mode of birth. DNAm was quantified using Illumina Infinium Human Methylation 450 K BeadChip in cord blood (at birth) and in peripheral blood (at 7 and 15-17 years). Analyses controlled for maternal age, education, smoking during pregnancy, child sex, gestational week at birth, and batch effects. We also examined interactions of mode of birth with breastfeeding practices and mother-infant bonding. In cord blood, two cytosine-phosphate-guanine dinucleotides (cg05230316; cg13230077) were linked to mode of birth (
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2066223-3
ISSN	1939-0599 ; 0012-1649
ISSN (online)	1939-0599
ISSN	0012-1649
DOI	10.1037/dev0001722
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Article ; Online: 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, Ivona / Horvatiček, Marina / Perić, Maja / Nikolić, Barbara / Holuka, Cyrielle / Klasić, Marija / Ivanišević, Marina / Starčević, Mirta / Desoye, Gernot / Hranilović, Dubravka / Turner, Jonathan D / Štefulj, Jasminka

Clinical epigenetics

2024 Volume 16, Issue 1, Page(s) 4

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Male ; Infant, Newborn ; Pregnancy ; Female ; Adolescent ; DNA Methylation ; Serotonin/metabolism ; Fetal Blood/metabolism ; Cesarean Section ; Diabetes, Gestational/genetics ; Blood Cells/metabolism ; Glucose/metabolism ; Serotonin Plasma Membrane Transport Proteins/genetics ; Serotonin Plasma Membrane Transport Proteins/metabolism
Chemical Substances	Serotonin (333DO1RDJY) ; Glucose (IY9XDZ35W2) ; SLC6A4 protein, human ; Serotonin Plasma Membrane Transport Proteins
Language	English
Publishing date	2024-01-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553921-8
ISSN	1868-7083 ; 1868-7075
ISSN (online)	1868-7083
ISSN	1868-7075
DOI	10.1186/s13148-023-01610-w
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Article ; Online: Methylation of serotonin regulating genes in cord blood cells

Ivona Bečeheli / Marina Horvatiček / Maja Perić / Barbara Nikolić / Cyrielle Holuka / Marija Klasić / Marina Ivanišević / Mirta Starčević / Gernot Desoye / Dubravka Hranilović / Jonathan D. Turner / Jasminka Štefulj

Clinical Epigenetics, Vol 16, Iss 1, Pp 1-

association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

2024 Volume 18

Abstract: Abstract 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 ... ...

Abstract	Abstract 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 ...
Keywords	Early-life adversity ; Maternal obesity ; ALSPAC ; Epigenetic ; DoHAD ; Sex differences ; Medicine ; R ; Genetics ; QH426-470
Subject code	570 ; 610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: A Holistic View of the Goto-Kakizaki Rat Immune System: Decreased Circulating Immune Markers in Non- Obese Type 2 Diabetes.

Seal, Snehaa V / Henry, Mathilde / Pajot, Clémentine / Holuka, Cyrielle / Bailbé, Danielle / Movassat, Jamileh / Darnaudéry, Muriel / Turner, Jonathan D

Frontiers in immunology

2022 Volume 13, Page(s) 896179

Abstract: Type-2 diabetes is a complex disorder that is now considered to have an immune component, with functional impairments in many immune cell types. Type-2 diabetes is often accompanied by comorbid obesity, which is associated with low grade inflammation. ... ...

Abstract	Type-2 diabetes is a complex disorder that is now considered to have an immune component, with functional impairments in many immune cell types. Type-2 diabetes is often accompanied by comorbid obesity, which is associated with low grade inflammation. However,the immune status in Type-2 diabetes independent of obesity remains unclear. Goto-Kakizaki rats are a non-obese Type-2 diabetes model. The limited evidence available suggests that Goto-Kakizaki rats have a pro-inflammatory immune profile in pancreatic islets. Here we present a detailed overview of the adult Goto-Kakizaki rat immune system. Three converging lines of evidence: fewer pro-inflammatory cells, lower levels of circulating pro-inflammatory cytokines, and a clear downregulation of pro-inflammatory signalling in liver, muscle and adipose tissues indicate a limited pro-inflammatory baseline immune profile outside the pancreas. As Type-2 diabetes is frequently associated with obesity and adipocyte-released inflammatory mediators, the pro-inflammatory milieu seems not due to Type-2 diabetes
MeSH term(s)	Animals ; Biomarkers ; Diabetes Mellitus, Type 2 ; Immune System ; Obesity ; Rats ; Rats, Wistar
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-05-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.896179
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Article ; Online: The epigenetic hallmark of early-life α-hexabromocyclododecane exposure: From cerebellar 6-mA levels to locomotor performance in adulthood.

Holuka, Cyrielle / Morel, Chloé / Roth, Sarah / Lamartinière, Yordenca / Mériaux, Sophie B / Paoli, Justine / Guébels, Pauline / Duca, Radu C / Godderis, Lode / van Nieuwenhuyse, An / Kremarik-Bouillaud, Pascaline / Cariou, Ronan / Emond, Claude / Schroeder, Henri / Turner, Jonathan D / Grova, Nathalie

Environment international

2023 Volume 178, Page(s) 108103

Abstract: There is a growing evidence that methylation at the ... ...

Abstract	There is a growing evidence that methylation at the N
MeSH term(s)	Male ; Animals ; Rats ; Female ; Pregnancy ; Chromatography, Liquid ; Rats, Wistar ; Placenta/metabolism ; Tandem Mass Spectrometry ; Hydrocarbons, Brominated/toxicity ; Hydrocarbons, Brominated/metabolism ; Flame Retardants/toxicity ; Flame Retardants/metabolism ; Cerebellum/metabolism ; Epigenesis, Genetic
Chemical Substances	hexabromocyclododecane (5I9835JO3M) ; Hydrocarbons, Brominated ; Flame Retardants
Language	English
Publishing date	2023-07-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	554791-x
ISSN	1873-6750 ; 0160-4120
ISSN (online)	1873-6750
ISSN	0160-4120
DOI	10.1016/j.envint.2023.108103
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Article: Adverse Life Trajectories Are a Risk Factor for SARS-CoV-2 IgA Seropositivity.

Holuka, Cyrielle / Snoeck, Chantal J / Mériaux, Sophie B / Ollert, Markus / Krüger, Rejko / Turner, Jonathan D / The Con-Vince Consortium

Journal of clinical medicine

2021 Volume 10, Issue 10

Abstract: Asymptomatic individuals, called "silent spreaders" spread SARS-CoV-2 efficiently and have complicated control of the ongoing COVID-19 pandemic. As seen in previous influenza pandemics, socioeconomic and life-trajectory factors are important in disease ... ...

Abstract	Asymptomatic individuals, called "silent spreaders" spread SARS-CoV-2 efficiently and have complicated control of the ongoing COVID-19 pandemic. As seen in previous influenza pandemics, socioeconomic and life-trajectory factors are important in disease progression and outcome. The demographics of the asymptomatic SARS-CoV-2 carriers are unknown. We used the CON-VINCE cohort of healthy, asymptomatic, and oligosymptomatic individuals that is statistically representative of the overall population of Luxembourg for age, gender, and residency to characterise this population. Gender (male), not smoking, and exposure to early-life or adult traumatic experiences increased the risk of IgA seropositivity, and the risk associated with early-life exposure was a dose-dependent metric, while some other known comorbidities of active COVID-19 do not impact it. As prior exposure to adversity is associated with negative psychobiological reactions to external stressors, we recorded psychological wellbeing during the study period. Exposure to traumatic events or concurrent autoimmune or rheumatic disease were associated with a worse evolution of anxiety and depressive symptoms throughout the lockdown period. The unique demographic profile of the "silent spreaders" highlights the role that the early-life period plays in determining our lifelong health trajectory and provides evidence that the developmental origins of health and disease is applicable to infectious diseases.
Language	English
Publishing date	2021-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10102159
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Article ; Online: Adverse Life Trajectories Are a Risk Factor for SARS-CoV-2 IgA Seropositivity

Cyrielle Holuka / Chantal J. Snoeck / Sophie B. Mériaux / Markus Ollert / Rejko Krüger / Jonathan D. Turner / the CON-VINCE Consortium

Journal of Clinical Medicine, Vol 10, Iss 2159, p

2021 Volume 2159

Abstract: Asymptomatic individuals, called “silent spreaders” spread SARS-CoV-2 efficiently and have complicated control of the ongoing COVID-19 pandemic. As seen in previous influenza pandemics, socioeconomic and life-trajectory factors are important in disease ... ...

Abstract	Asymptomatic individuals, called “silent spreaders” spread SARS-CoV-2 efficiently and have complicated control of the ongoing COVID-19 pandemic. As seen in previous influenza pandemics, socioeconomic and life-trajectory factors are important in disease progression and outcome. The demographics of the asymptomatic SARS-CoV-2 carriers are unknown. We used the CON-VINCE cohort of healthy, asymptomatic, and oligosymptomatic individuals that is statistically representative of the overall population of Luxembourg for age, gender, and residency to characterise this population. Gender (male), not smoking, and exposure to early-life or adult traumatic experiences increased the risk of IgA seropositivity, and the risk associated with early-life exposure was a dose-dependent metric, while some other known comorbidities of active COVID-19 do not impact it. As prior exposure to adversity is associated with negative psychobiological reactions to external stressors, we recorded psychological wellbeing during the study period. Exposure to traumatic events or concurrent autoimmune or rheumatic disease were associated with a worse evolution of anxiety and depressive symptoms throughout the lockdown period. The unique demographic profile of the “silent spreaders” highlights the role that the early-life period plays in determining our lifelong health trajectory and provides evidence that the developmental origins of health and disease is applicable to infectious diseases.
Keywords	SARS-CoV-2 ; COVID-19 ; early-life adversity ; adult traumatic events ; psychosocial adversity ; relative risk ; Medicine ; R
Subject code	360
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

Holuka, Cyrielle / Merz, Myriam P / Fernandes, Sara B / Charalambous, Eleftheria G / Seal, Snehaa V / Grova, Nathalie / Turner, Jonathan D

International journal of molecular sciences

2020 Volume 21, Issue 14

Abstract: A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, ... ...

Abstract	A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.
MeSH term(s)	Betacoronavirus/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Disease Susceptibility/immunology ; Healthcare Disparities ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Risk Factors ; SARS-CoV-2 ; Social Class ; Socioeconomic Factors ; Stress, Psychological/immunology
Keywords	covid19
Language	English
Publishing date	2020-07-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21145094
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