Publications by authors named "Katri Räikkönen"

319 Publications

Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.

Pregnancy Hypertens 2021 Jun 2;25:116-122. Epub 2021 Jun 2.

Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland.

Objectives: Maternal serum inhibin-A, pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine artery pulsatility index (UtA PI) were analysed to study their ability to predict pre-eclampsia (PE).

Study Design: Serial serum samples for the nested case-control study were collected prospectively at 12-14, 18-20 and 26-28 weeks of gestation from 11 women who later developed early-onset PE (EO PE, diagnosis < 34 + 0 weeks of gestation), 34 women who developed late-onset PE (LO PE, diagnosis ≥ 34 + 0 weeks) and 89 controls.

Main Outcome Measures: Gestational age -adjusted multiples of the median (MoM) values were calculated for biomarker concentrations. Multivariate regression analyses were performed to combine first trimester biomarkers, previously reported results on PlGF, maternal risk factors and UtA PI. Area under curve (AUC) values and 95% confidence intervals (CIs) for the prediction of PE and its subtypes were calculated.

Results: A high first trimester inhibin-A predicted PE (AUC 0.618, 95%CI, 0.513-0.724), whereas PAPP-A and PlGF predicted only EO PE (0.701, 0.562-0.840 and 0.798, 0.686-0.909, respectively). At 26-28 weeks PAPP-A2 and inhibin-A predicted all PE subtypes. In the multivariate setting inhibin-A combined with maternal pre-pregnancy body mass index, prior PE and mean UtA PI predicted PE (0.811,0.726-0.896) and LO PE (0.824, 0.733-0.914).

Conclusions: At first trimester inhibin-A show potential ability to predict not only EO PE but also LO PE whereas PlGF and PAPP-A predict only EO PE. At late second trimester inhibin-A and PAPP-A2 might be useful for short-term prediction of PE.
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http://dx.doi.org/10.1016/j.preghy.2021.05.024DOI Listing
June 2021

Association of Very Preterm Birth or Very Low Birth Weight With Intelligence in Adulthood: An Individual Participant Data Meta-analysis.

JAMA Pediatr 2021 May 28. Epub 2021 May 28.

Department of Psychology, University of Warwick, Coventry, United Kingdom.

Importance: Birth before 32 weeks' gestation (very preterm [VPT]) and birth weight below 1500 g (very low birth weight [VLBW]) have been associated with lower cognitive performance in childhood. However, there are few investigations of the association of neonatal morbidities and maternal educational levels with the adult cognitive performance of individuals born VPT or VLBW (VPT/VLBW).

Objective: To assess differences in adult IQ between VPT/VLBW and term-born individuals and to examine the association of adult IQ with cohort factors, neonatal morbidities, and maternal educational level among VPT/VLBW participants.

Data Sources: Systematic review of published data from PubMed and meta-analysis of individual participant data (IPD) of cohorts from 2 consortia (Research on European Children and Adults Born Preterm [RECAP] and Adults Born Preterm International Collaboration [APIC]).

Study Selection: The meta-analysis included prospective longitudinal cohort studies that assessed the full-scale IQ of adults born VPT or VLBW and respective control groups comprising term-born adults.

Data Extraction And Synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for analyses of individual participant data and identified 8 studies that provided data from 2135 adults (1068 VPT/VLBW and 1067 term-born participants) born between 1978 and 1995. Meta-analyses of IPD were performed using a 1-stage approach, treating VPT birth or VLBW and cohort as random effects.

Main Outcomes And Measures: Full-scale IQ scores were converted to z scores within each cohort using the combined SD of VPT/VLBW participants and a control group of term-born participants, with scores centered on the mean of the control group.

Results: A total of 426 records were identified and screened. After exclusions, 13 studies were included in the aggregate meta-analysis. The IPD meta-analysis included 8 of the 9 RECAP and APIC cohorts with adult IQ data. The mean (SD) age among the 8 IPD cohorts was 24.6 (4.3) years, and 1163 participants (54.5%) were women. In unadjusted analyses, VPT/VLBW participants had mean adult IQ scores that were 0.78 SD (95% CI, -0.90 to -0.66 SD) lower than term-born participants, equivalent to a difference of 12 IQ points. Among VPT/VLBW participants, lower gestational age (score difference per week of gestation, 0.11; 95% CI, 0.07-0.14), lower birth weight z scores (score difference per 1.0 SD, 0.21; 95% CI, 0.14-0.28), the presence of neonatal bronchopulmonary dysplasia (score difference, -0.16; 95% CI, -0.30 to -0.02) or any grade of intraventricular hemorrhage (score difference, -0.19; 95% CI, -0.33 to -0.05), and lower maternal educational level (score difference, 0.26; 95% CI, 0.17-0.35) were all significantly associated with lower IQ scores in adulthood.

Conclusions And Relevance: In this IPD meta-analysis, lower gestational age, lower weight for gestational age, neonatal morbidities, and lower maternal educational levels were all important risk factors associated with lower IQ among young adults born VPT or VLBW.
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http://dx.doi.org/10.1001/jamapediatrics.2021.1058DOI Listing
May 2021

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Neuropsychopharmacology 2021 May 25. Epub 2021 May 25.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.
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http://dx.doi.org/10.1038/s41386-021-01023-4DOI Listing
May 2021

Maternal Hypertensive Pregnancy Disorders and Mental and Behavioral Disorders in the Offspring: a Review.

Curr Hypertens Rep 2021 05 13;23(5):30. Epub 2021 May 13.

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Haartmaninkatu 3, P.O. Box 9, FI-00014 University of Helsinki, Helsinki, Finland.

Purpose Of Review: We review here recent original research and meta-analytic evidence on the associations of maternal hypertensive pregnancy disorders and mental and behavioral disorders in the offspring.

Recent Findings: Seven meta-analyses and 11 of 16 original research studies published since 2015 showed significant associations between maternal hypertensive pregnancy disorders and offspring mental and behavioral disorders. Evidence was most consistent in meta-analyses and high-quality cohort studies. The associations, independent of familial confounding, were observed on different mental and behavioral disorders in childhood and schizophrenia in adulthood. Preterm birth and small-for-gestational age birth emerged as possible moderators and mediators of the associations. Cross-sectional and case-control studies yielded inconsistent findings, but had lower methodological quality. Accumulating evidence from methodologically sound studies shows that maternal hypertensive pregnancy disorders are associated with an increased risk of mental and behavioral disorders in the offspring in childhood. More studies on adult mental disorders are needed.
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http://dx.doi.org/10.1007/s11906-021-01141-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116290PMC
May 2021

Characteristics of epigenetic aging across gestational and perinatal tissues.

Clin Epigenetics 2021 Apr 29;13(1):97. Epub 2021 Apr 29.

Department of Translational Psychiatry, Max Planck Institute of Psychiatry, München, Germany.

Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns-especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues.

Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues.

Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.
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http://dx.doi.org/10.1186/s13148-021-01080-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082803PMC
April 2021

Links between television exposure and toddler dysregulation: Does culture matter?

Infant Behav Dev 2021 May 18;63:101557. Epub 2021 Apr 18.

Washington State University, USA. Electronic address:

Television exposure in early childhood has increased, with concerns raised regarding adverse effects on social-emotional development, and emerging self-regulation in particular. The present study addressed television exposure (i.e., amount of time watching TV) and its associations with toddler behavioral/emotional dysregulation, examining potential differences across 14 cultures. The sample consisted of an average of 60 toddlers from each of the 14 countries from the Joint Effort Toddler Temperament Consortium (JETTC; Gartstein & Putnam, 2018). Analyses were conducted relying on the multi-level modeling framework (MLM), accounting for between- and within-culture variability, and examining the extent to which TV exposure contributions were universal vs. variable across sites. Effects of time watching TV were evaluated in relation to temperament reactivity and regulation, as well as measures of emotional reactivity, attention difficulties, and aggression. Results indicated that more time spent watching TV was associated with higher ratings on Negative Emotionality, emotional reactivity, aggression, and attention problems, as well as lower levels of soothability. However, links between TV exposure and both attention problems and soothability varied significantly between cultures. Taken together, results demonstrate that increased time spent watching television was generally associated with dysregulation, although effects were not consistently uniform, but rather varied as a function of culturally-dependent contextual factors.
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http://dx.doi.org/10.1016/j.infbeh.2021.101557DOI Listing
May 2021

An EPIC predictor of gestational age and its application to newborns conceived by assisted reproductive technologies.

Clin Epigenetics 2021 Apr 19;13(1):82. Epub 2021 Apr 19.

Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.

Background: Gestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. DNA methylation at birth has proven to be an accurate predictor of gestational age. Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART).

Methods: We built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)-a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study-a prospective pregnancy cohort of Finnish women.

Results: Our new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks (R = 0.724, median absolute deviation (MAD) = 3.14 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age (R = 0.767, MAD = 3.7 days).

Conclusions: We present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.
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http://dx.doi.org/10.1186/s13148-021-01055-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056641PMC
April 2021

Anti-inflammatory Potential of Maternal Diet During Pregnancy: A Promise to Promote the Mental Health of Children.

Biol Psychiatry 2021 03;89(6):536-538

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.biopsych.2020.12.005DOI Listing
March 2021

Physical Activity, Mental Health, and Well-Being in Very Pre-Term and Term Born Adolescents: An Individual Participant Data Meta-Analysis of Two Accelerometry Studies.

Int J Environ Res Public Health 2021 02 10;18(4). Epub 2021 Feb 10.

Department of Psychology, University of Warwick, Coventry CV4 7AL, UK.

This study examined whether physical activity is associated with better mental health and well-being among very preterm (≤32 weeks) and term born (≥37 weeks) adolescents alike or whether the associations are stronger in either of the groups. Physical activity was measured with accelerometry in children born very preterm and at term in two cohorts, the Basel Study of Preterm Children (BSPC; 40 adolescents born ≤32 weeks of gestation and 59 term born controls aged 12.3 years) and the Millennium Cohort Study (MCS; 45 adolescents born ≤32 weeks of gestation and 3137 term born controls aged 14.2 years on average). In both cohorts, emotional and behavioral problems were mother-reported using the Strengths and Difficulties Questionnaire. Subjective well-being was self-reported using the Kidscreen-52 Questionnaire in the BSPC and single items in the MCS. Hierarchical regressions with 'preterm status × physical activity'-interaction effects were subjected to individual participant data (IPD) meta-analysis. IPD meta-analysis showed that higher levels of physical activity were associated with lower levels of peer problems, and higher levels of psychological well-being, better self-perception/body image, and school related well-being. Overall, the effect-sizes were small and the associations did not differ significantly between very preterm and term born adolescents. Future research may examine the mechanisms behind effects of physical activity on mental health and wellbeing in adolescence as well as which type of physical activity might be most beneficial for term and preterm born children.
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http://dx.doi.org/10.3390/ijerph18041735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916780PMC
February 2021

Combined effects of genotype and childhood adversity shape variability of DNA methylation across age.

Transl Psychiatry 2021 Feb 1;11(1):88. Epub 2021 Feb 1.

Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.

Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DNAm at birth is best explained by the joint effects of genotype and prenatal environment. Here, we extend these analyses to postnatal stressors. We investigated the contribution of CA, cis genotype (G), and their additive (G + CA) and interactive (G × CA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA, which was assessed retrospectively using self-reports or verified through social services and registries. For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G + CA or G × CA but almost never by CA alone. Across ages and tissues, 1672 DNAm sites showed consistency of the best model in all five cohorts, with G × CA interactions explaining most variance. The consistent G × CA sites mapped to genes enriched in brain-specific transcripts and Gene Ontology terms related to development and synaptic function. Interaction of CA with genotypes showed the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.
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http://dx.doi.org/10.1038/s41398-020-01147-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851167PMC
February 2021

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Hum Mol Genet 2021 Apr;30(5):393-409

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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http://dx.doi.org/10.1093/hmg/ddab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112PMC
April 2021

Presleep physiological stress is associated with a higher cortical arousal in sleep and more consolidated REM sleep.

Stress 2021 Jan 18:1-9. Epub 2021 Jan 18.

Research Program Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

How sleep regulates physiological stress in healthy individuals is not well understood. We explored the associations between naturally occurring pre-sleep physiological arousal and EEG power spectral density together with rapid eye movement sleep (REMS) continuity. One hundred and fifty-four individuals (mean age 16.9, SD 0.1 years) collected five samples of saliva between the evening (mean time 18:20) and bedtime (mean 23:00) by using swabs, and underwent an overnight in-home polysomnography. We calculated spectral density for REMS and non-rapid eye movement sleep (non-REMS), and the number and duration of REMS arousals (<15 s) during sleep. An observational design allowed for measurement of natural variation in physiological and sleep arousal. Increasing cortisol levels toward bedtime were associated with higher EEG power spectral density at all frequency ranges in frontal locations, the highest association being for the beta1 frequency band. In central locations, the associations were pronounced for beta1 and beta2 bands. Higher overall cortisol levels in the evening were associated with less fragmented REMS. Presleep arousal was not associated with sleep staging. Physiological arousal toward bedtime was associated with EEG power spectral density values during sleep specifically at high EEG frequencies. This may represent a compensatory mechanism that serves as an adaptation to stress, since the REMS was more continuous along a higher physiological arousal level in the evening. Although causality cannot be inferred, a design with nonmanipulated physiological stress followed by naturally timed sleep at home provides new insights into stress regulation homeostasis.
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http://dx.doi.org/10.1080/10253890.2020.1869936DOI Listing
January 2021

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

Mol Psychiatry 2021 Jan 8. Epub 2021 Jan 8.

Department of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, 33520, Finland.

DNA 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; Bonferroni correction). In cord blood samples of 2425 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 peripheral 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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http://dx.doi.org/10.1038/s41380-020-00987-xDOI Listing
January 2021

Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation.

Mol Psychiatry 2021 Jan 7. Epub 2021 Jan 7.

Erasmus MC, University Medical Center Rotterdam, Generation R Study Group, Rotterdam, The Netherlands.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.
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http://dx.doi.org/10.1038/s41380-020-00976-0DOI Listing
January 2021

A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders.

Neurobiol Stress 2020 Nov 21;13:100275. Epub 2020 Nov 21.

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Finland.

Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes.

Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1-10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child's age of 2.3-5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583).

Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = -0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met.

Conclusions: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders.
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http://dx.doi.org/10.1016/j.ynstr.2020.100275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739178PMC
November 2020

Maternal haemoglobin levels in pregnancy and child DNA methylation: a study in the pregnancy and childhood epigenetics consortium.

Epigenetics 2021 Jan 11:1-13. Epub 2021 Jan 11.

Department of Immunobiochemistry, National Institute of Perinatology, Mexico City, Mexico.

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.
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http://dx.doi.org/10.1080/15592294.2020.1864171DOI Listing
January 2021

The association between sleep-wake ratio and overnight picture recognition is moderated by BDNF genotype.

Neurobiol Learn Mem 2021 01 27;177:107353. Epub 2020 Nov 27.

Sleepwell Research Program, Faculty of Medicine, University of Helsinki, P.O. Box 9, 00014 Helsinki, Finland. Electronic address:

A wealth of studies supports the role of sleep in memory performance. Experimentally controlled studies indicate that prolonged wake after memory encoding is detrimental for memory outcome whereas sleep protects from wake-time interference and promotes memory consolidation. We examined how the natural distribution of wake and sleep between encoding and retrieval associated with overnight picture recognition accuracy among 161 adolescents following their typical sleep schedule with an in-home polysomnography. The memorized pictures varied in their level of arousal (calm to exciting) and valence (negative to positive). Suspecting genotypic influence on the sensitivity for sleep/wake dynamics, we also assessed if these associations were affected by known gene polymorphisms involved in neural plasticity and sleep homeostasis: brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-methyltransferase (COMT) Val158Met. In the whole sample, overnight recognition accuracy was associated with the levels of arousal and valence of the pictures, but not with sleep percentage (i.e. the percentage of time spent asleep between memory encoding and retrieval). While the allelic status of BDNF or COMT did not have any main effect on recognition accuracy, a significant moderation by BDNF Val66Met was found (p = .004): the subgroup homozygous for valine allele showed positive association between sleep percentage and recognition accuracy. This was underlain by detrimental influence of wake, rather than by any memory benefit of sleep. Our results complement the mounting evidence that the relation between sleep and memory performance is moderated by BDNF Val66Met. Further studies are needed to clarify the specific mechanisms.
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http://dx.doi.org/10.1016/j.nlm.2020.107353DOI Listing
January 2021

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

Genome Med 2020 11 25;12(1):105. Epub 2020 Nov 25.

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.

Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.

Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P = 1; childhood P = 2.00 × 10; adolescence P = 2.10 × 10).

Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.
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http://dx.doi.org/10.1186/s13073-020-00810-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687793PMC
November 2020

Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis.

Transl Psychiatry 2020 11 12;10(1):398. Epub 2020 Nov 12.

Clinical Child & Family Studies, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10. In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.
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http://dx.doi.org/10.1038/s41398-020-01058-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665047PMC
November 2020

Maternal Antenatal Corticosteroid Treatment and Childhood Mental and Behavioral Disorders-Reply.

JAMA 2020 10;324(15):1570-1571

Department of Public Health Solutions, THL Finnish Institute for Health and Welfare, Helsinki.

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http://dx.doi.org/10.1001/jama.2020.15449DOI Listing
October 2020

Common Core Assessments in follow-up studies of adults born preterm-Recommendation of the Adults Born Preterm International Collaboration.

Paediatr Perinat Epidemiol 2021 May 29;35(3):371-387. Epub 2020 Sep 29.

Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Vic., Australia.

Background: Of all newborns, 1%-2% are born very preterm (VP; <32 weeks) or with very low birthweight (VLBW; ≤1500 g). Advances in prenatal and neonatal care have substantially improved their survival, and the first generations who have benefited from these advances are now entering middle age. While most lead healthy lives, on average these adults are characterised by a number of adversities. These include cardiometabolic risk factors, airway obstruction, less physical activity, poorer visual function, lower cognitive performance, and a behavioural phenotype that includes inattention and internalising and socially withdrawn behaviour that may affect life chances and quality of life. Outcomes in later adulthood are largely unknown, and identifying trajectories of risk or resilience is essential in developing targeted interventions. Joint analyses of data and maintenance of follow-up of cohorts entering adulthood are essential. Such analyses are ongoing within the Adults Born Preterm International Collaboration (APIC; www.apic-preterm.org). Joint analyses require data harmonisation, highlighting the importance of consistent assessment methodologies.

Objective: To present an expert recommendation on Common Core Assessments to be used in follow-up assessments of adults born preterm.

Methods: Principles of Common Core Assessments were discussed at APIC meetings. Experts for each specific outcome domain wrote the first draft on assessments pertaining to that outcome. These drafts were combined and reviewed by all authors. Consensus was reached by discussion at APIC meetings.

Results: We present a recommendation by APIC experts on consistent measures to be used in adult follow-up assessments.

Conclusions: The recommendation encompasses both "core" measures which we recommend to use in all assessments of adults born preterm that include the particular outcome. This will allow comparability between time and location. The recommendation also lists optional measures, focusing on current gaps in knowledge. It includes sections on study design, cardiometabolic and related biomarkers, biological samples, life style, respiratory, ophthalmic, cognitive, mental health, personality, quality of life, sociodemographics, social relationships, and reproduction.
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http://dx.doi.org/10.1111/ppe.12694DOI Listing
May 2021

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Nat Hum Behav 2021 01 28;5(1):59-70. Epub 2020 Sep 28.

Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
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http://dx.doi.org/10.1038/s41562-020-00956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116623PMC
January 2021

Maternal antenatal stress and mental and behavioral disorders in their children.

J Affect Disord 2021 01 15;278:57-65. Epub 2020 Sep 15.

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Finland.

Background: Maternal antenatal stress, including symptoms of depression, anxiety and perceived stress, is associated with mental and behavioral problems in children. Whether it is associated with child mental and behavioral disorders remains uncertain. We examined if maternal antenatal symptoms of depression, anxiety and perceived stress were associated with mental and behavioral disorders in their children, if the associations varied according to gestational week, stress type, fluctuating or consistently high symptoms, and if they were driven by maternal or paternal lifetime mood or anxiety disorders.

Methods: 3365 mothers participating in the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiologic Studies Depression Scale, the State Anxiety Inventory and the Perceived Stress Scale up to 14 times throughout pregnancy. The Care Register for Health Care provided data on mental and behavioral (including neurodevelopmental) disorders for their children from birth (11/07/2006-07/24/2010) until 12/31/2016 and for parental lifetime mood and anxiety disorders until 12/31/2016.

Results: The hazard of any childhood mental and behavioral disorder (HR=1.91, 95% CI: 1.39-2.51) was significantly higher for children whose mothers reported consistently high in comparison to consistently low levels of all types of stress throughout pregnancy. The associations remained significant when adjusted for maternal and paternal lifetime mood and anxiety disorders (and their comorbidity and timing and mood disorder type).

Conclusion: Maternal antenatal stress is associated with higher risk of childhood mental and behavioral disorders. Efforts to reduce maternal antenatal stress should be given a high priority to improve child mental health.
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http://dx.doi.org/10.1016/j.jad.2020.09.063DOI Listing
January 2021

Maternal Psychological Resilience During Pregnancy and Newborn Telomere Length: A Prospective Study.

Am J Psychiatry 2021 02 11;178(2):183-192. Epub 2020 Sep 11.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology, Berlin (Verner, Buss, Entringer); Department of Psychiatry, San Francisco School of Medicine, University of California, San Francisco (Epel); Department of Psychology and Logopedics, University of Helsinki, Helsinki (Lahti-Pulkkinen, Räikkönen); Department of Public Health Solutions, THL National Institute for Health and Welfare, Helsinki and Oulu, Finland, PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, and Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki (Kajantie); Department of Pediatrics and UC Irvine Development, Health, and Disease Research Program, University of California, Irvine (Buss, Wadhwa, Entringer); Department of Biochemistry and Biophysics (Lin, Blackburn) and Department of Microbiology and Immunology (Blackburn), University of California, San Francisco; Department of Psychiatry and Human Behavior, Department of Obstetrics and Gynecology, and Department of Epidemiology, School of Medicine, University of California, Irvine (Wadhwa).

Objective: In the context of the importance of elucidating the determinants of the initial, newborn setting of telomere length (TL), it is increasingly evident that maternal stress and stress-related processes during pregnancy play a major role. Although psychological resilience may function as a buffer, research in this area has not yet examined its potential role vis-à-vis that of stress. The authors examined the relationship between maternal psychological resilience during pregnancy and newborn TL.

Methods: In a sample of 656 mother-child dyads from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction cohort, multiple serial assessments were conducted over the course of pregnancy to quantify maternal stress, negative and positive emotional responses to pregnancy events, positive affect, and perceived social support. Principal component analysis identified two latent factors: stress and positivity. A measure of resilience was computed by regressing the positivity factor on the stress factor, in order to quantify positivity after accounting for stress. TL was measured using quantitative polymerase chain reaction in leukocytes extracted from cord blood shortly after birth. Linear regression was used to predict newborn TL from maternal resilience during pregnancy, adjusting for other potential determinants.

Results: Maternal stress significantly predicted shorter newborn TL (β=-0.079), and positivity significantly predicted longer TL (β=0.135). Maternal resilience (positivity accounting for stress) was significantly and positively associated with newborn TL (β=0.114, 95% CI=0.035, 0.189), with each standard deviation increase in resilience predicting 12% longer newborn TL.

Conclusions: The results indicate that maternal psychological resilience may exert a salubrious effect on offspring telomere biology and highlight the importance of enhancing maternal mental health and well-being during pregnancy.
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http://dx.doi.org/10.1176/appi.ajp.2020.19101003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855094PMC
February 2021

Eveningness associates with lower physical activity from pre- to late adolescence.

Sleep Med 2020 10 21;74:189-198. Epub 2020 Jul 21.

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Objective: Adolescence is often associated with decline in physical activity (PA) and a circadian shift towards eveningness, but it is not known whether these transitions are intertwined. We explored longitudinally and in cross-section how chronotype and genetic liability for morningness associate with PA as self-reported and measured by actigraphy in early and late adolescence.

Methods: Our sample comes from a longitudinal Finnish community-cohort born in 1998 with information on actigraph-based PA and objectively measured sleep-wake rhythm based on midpoint of sleep at ages 12 (N = 353, girls = 187) and 17 (N = 171, girls = 98). Information on self-reported circadian preference and subjective PA was available at age 17. The summarized genetic effects of multiple single nucleotide polymorphism for morningness was assessed by calculating polygenic score (PGS) based on the results on a recent genome-wide association study (GWAS).

Results: PA declined by 40% (p < 0.0001) in boys and by 32% in girls (p < 0.0001) from age 12 to 17. Later midpoint of sleep correlated significantly with lower level of general, light and moderate to vigorous PA only at age 12 (all p < 0.05) but not at age 17 (all p ≥ 0.36). However, those with circadian preference more towards eveningness at age 17 had more sedentary behavior (p < 0.01) and a lower level of general (p = 0.01), light (p < 0.01) and moderate to vigorous PA (p < 0.05). They also had poorer subjective assessment of their fitness level (p < 0.01) and they exercised less (all p ≤ 0.05). The decline in objectively measured PA and increase in sedentary behavior from age 12 to 17 was emphasized among those with circadian preference towards eveningness (p < 0.05). PGS for morningness was not significantly associated with PA in adolescence (all p ≥ 0.13).

Conclusions: Findings of this study highlighted the influence of circadian preference on physical activity behavior in adolescence. Self-assessed circadian preference towards eveningness associated with lower PA and greater decline of it during adolescence. Furthermore, PA declined significantly especially among boys from early to late adolescence. Interventions encouraging physical activity should target specifically evening-oriented adolescents.
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http://dx.doi.org/10.1016/j.sleep.2020.07.021DOI Listing
October 2020

Maternal pre-pregnancy overweight and gestational diabetes and dietary intakes among young adult offspring.

Nutr Diabetes 2020 07 23;10(1):26. Epub 2020 Jul 23.

National Institute for Health and Welfare, Helsinki, Oulu, Finland.

Background/objectives: Maternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m) or GDM are associated with dietary quality or intake in adult offspring.

Subjects/methods: Participants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537).

Results: Among men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [-587.2 kJ/day (-1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (-0.38, 1.18); women 0.25 (-0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (-0.62, 0.80); women -0.17 (-0.93, 0.59)].

Conclusions: Our study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.
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http://dx.doi.org/10.1038/s41387-020-00129-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378069PMC
July 2020

Depression, obesity and their comorbidity during pregnancy: effects on the offspring's mental and physical health.

Mol Psychiatry 2021 02 6;26(2):462-481. Epub 2020 Jul 6.

Biological Psychiatry Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

Depression and obesity represent two of the most common complications during pregnancy and are associated with severe health risks for both the mother and the child. Although several studies have analysed the individual effects of depression or obesity on the mothers and their children, the effects associated with the co-occurrence of both disorders have so far been poorly investigated. The relationship between depression and obesity is very complex and it is still unclear whether maternal depression leads to obesity or vice versa. It is well known that the intrauterine environment plays an important role in mediating the effects of both depression and obesity in the mother on the fetal programming, increasing the child's risk to develop negative outcomes.
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http://dx.doi.org/10.1038/s41380-020-0813-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850968PMC
February 2021

Polygenic prediction of the risk of perinatal depressive symptoms.

Depress Anxiety 2020 09 5;37(9):862-875. Epub 2020 Jul 5.

Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Background: Perinatal depression carries adverse effects on maternal health and child development, but genetic underpinnings remain unclear. We investigated the polygenic risk of perinatal depressive symptoms.

Methods: About 742 women from the prospective Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction cohort were genotyped and completed the Center for Epidemiologic Studies Depression scale 14 times during the prenatal period and twice up to 12 months postpartum. Polygenic risk scores for major depressive disorder, bipolar disorder, schizophrenia, and cross-disorder were calculated using multiple p-value thresholds.

Results: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder, but not bipolar disorder, were associated with higher prenatal and postpartum depressive symptoms (0.8%-1% increase per one standard deviation increase in polygenic risk scores). Prenatal depressive symptoms accounted for and mediated the associations between the polygenic risk scores and postpartum depressive symptoms (effect size proportions-mediated: 52.2%-88.0%). Further, the polygenic risk scores were associated with 1.24-1.45-fold odds to belong to the group displaying consistently high compared with consistently low depressive symptoms through out the prenatal and postpartum periods.

Conclusions: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder in non-perinatal populations generalize to perinatal depressive symptoms and may afford to identify women for timely preventive interventions.
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http://dx.doi.org/10.1002/da.23066DOI Listing
September 2020

Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure.

Hypertension 2020 07 10;76(1):195-205. Epub 2020 Jun 10.

Department of Endocrinology (B.H.R.W., J.V.v.V.-O.), University Medical Center Groningen, University of Groningen, The Netherlands.

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with <1×10. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (<1×10) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with <0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 () and cg00716257 () determined by environmental effects acting on both systolic BP and methylation levels.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295009PMC
July 2020