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

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

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

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

scholarly journals Intra-uterine and Genetic Influences on the Relationship Between Size at Birth and Height in Later Life: Analysis in Twins

Twin Research ◽  
2001 ◽  
Vol 4 (5) ◽  
pp. 337-343 ◽  
Author(s):  
Richard G. IJzerman ◽  
Coen D.A. Stehouwer ◽  
Mirjam M. van Weissenbruch ◽  
Eco J. de Geus ◽  
Dorret I. Boomsma
Keyword(s):  
Birth Weight ◽  
Genetic Model ◽  
Model Fitting ◽  
Monozygotic Twins ◽  
Positive Association ◽  
Later Life ◽  
Birth Length ◽  
Dizygotic Twins ◽  
Genetic Source ◽  
Size At Birth

AbstractEpidemiological studies have consistently shown a positive association between size at birth (i.e. birth weight or birth length) and height in children, adolescents and adults. To examine whether this association is explained by genetic or nongenetic (intra-uterine) factors, we investigated birth weight, birth length and height in 60 dizygotic and 68 monozygotic adolescent twin pairs still living with their parents. Birth weight of the twins was obtained from their mothers. Height was measured in a standardised way. The mean age was 17±1.7 years for the dizygotic twins and 16±1.8 years for the monozygotic twins. Both dizygotic and monozygotic twins with the lowest birth weight from each pair had a height that was lower compared to their co-twins with the highest birth weight (dizygotic twins: 172.2±7.9 vs. 173.8±9.4 cm [p = 0.05]; monozygotic twins: 171.1±9.4 vs. 171.8±9.5 cm [p = 0.01]). Similarly, both dizygotic and monozygotic twins with the shortest birth length from each pair had a height that was lower compared to their co-twins with the longest birth length (dizygotic twins: 172.3±7.9 vs. 174.9±9.7 cm [p < 0.05]; monozygotic twins: 168.9±10.6 vs. 169.9±10.2 cm [p < 0.01]). In addition, intra-pair differences in birth weight and birth length were significantly associated with differences in height in both dizygotic twins (regression coefficient: 4.3 cm/kg [95% confidence interval: 1.0 to 7.5] and 0.96 cm/cm [0.17 to 1.74], respectively) and monozygotic twins (2.8 cm/kg [1.4 to 4.1] and 0.73 cm/cm [0.40 to 1.06], respectively). These associations were stronger in dizygotic than in monozygotic twins, but this difference was not statistically significant (for birth weight p = 0.4; and for birth length p = 0.6). However, genetic model fitting indicated that models incorporating a genetic source of the covariance gave a better description of the observed association of birth weight and length with height in later life than models not incorporating this genetic source. The results were similar for data on adult height after 12 years of follow-up in a subgroup of these twin pairs. These data suggest that the association between size at birth and height in later life is influenced by non-genetic intra-uterine and by genetic factors.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

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

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

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

Baseline surgical status and short-term mortality after extracorporeal membrane oxygenation for post-cardiotomy shock: a meta-analysis

Perfusion ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 246-254
Author(s):  
Mariusz Kowalewski ◽  
Giuseppe Raffa ◽  
Kamil Zieliński ◽  
Paolo Meani ◽  
Musab Alanazi ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Cardiogenic Shock ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Meta Analysis ◽  
Positive Association ◽  
Neurological Complications ◽  
Significant Positive Association ◽  
Membrane Oxygenation ◽  
Baseline Status

Objective: While reported mortality rates on post-cardiotomy extracorporeal membrane oxygenation vary from center to center, impact of baseline surgical status (elective/urgent/emergency/salvage) on mortality is still unknown. Methods: A systematic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using PubMed/Medline databases until March 2018 using the keywords “postcardiotomy,” “cardiogenic shock,” “extracorporeal membrane oxygenation,” and “extracorporeal life support.” Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and baseline surgical status. The correlations between mortality and percentage of elective/urgent/emergency cases were investigated. Inference analysis of baseline status and extracorporeal membrane oxygenation complications was conducted as well. Results: Twenty-two studies (conducted between 1993 and 2017) enrolling N = 2,235 post-cardiotomy extracorporeal membrane oxygenation patients were found. Patients were mostly of non-emergency status (65.2%). Overall in-hospital/30-day mortality event rate (95% confidence intervals) was 66.7% (63.3-69.9%). There were no differences in in-hospital/30-day mortality with respect to baseline surgical status in the subgroup analysis (test for subgroup differences; p = 0.406). Similarly, no differences between mortality in studies enrolling <50 versus ⩾50% of emergency/salvage cases was found: respective event rates were 66.9% (63.1-70.4%) versus 64.4% (57.3-70.8%); p = 0.525. Yet, there was a significant positive association between increasing percentage of emergency/salvage cases and rates of neurological complications (p < 0.001), limb complications (p < 0.001), and bleeding (p = 0.051). Incidence of brain death (p = 0.099) and sepsis (p = 0.134) was increased as well. Conclusion: Other factors than baseline surgical status may, to a higher degree, influence the mortality in patients treated with extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock. Baseline status, however, strongly influences the complication occurrence while on extracorporeal membrane oxygenation.

scholarly journals DNA methylation associated with postpartum depressive symptoms overlaps findings from a genome-wide association meta-analysis of depression

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Dana M. Lapato ◽  
Roxann Roberson-Nay ◽  
Robert M. Kirkpatrick ◽  
Bradley T. Webb ◽  
Timothy P. York ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Depressive Symptoms ◽  
Health Outcomes ◽  
Meta Analysis ◽  
Previous History ◽  
Depression Scale ◽  
Postpartum Depressive Symptoms ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Abstract Background Perinatal depressive symptoms have been linked to adverse maternal and infant health outcomes. The etiology associated with perinatal depressive psychopathology is poorly understood, but accumulating evidence suggests that understanding inter-individual differences in DNA methylation (DNAm) patterning may provide insight regarding the genomic regions salient to the risk liability of perinatal depressive psychopathology. Results Genome-wide DNAm was measured in maternal peripheral blood using the Infinium MethylationEPIC microarray. Ninety-two participants (46% African-American) had DNAm samples that passed all quality control metrics, and all participants were within 7 months of delivery. Linear models were constructed to identify differentially methylated sites and regions, and permutation testing was utilized to assess significance. Differentially methylated regions (DMRs) were defined as genomic regions of consistent DNAm change with at least two probes within 1 kb of each other. Maternal age, current smoking status, estimated cell-type proportions, ancestry-relevant principal components, days since delivery, and chip position served as covariates to adjust for technical and biological factors. Current postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale. Ninety-eight DMRs were significant (false discovery rate < 5%) and overlapped 92 genes. Three of the regions overlap loci from the latest Psychiatric Genomics Consortium meta-analysis of depression. Conclusions Many of the genes identified in this analysis corroborate previous allelic, transcriptomic, and DNAm association results related to depressive phenotypes. Future work should integrate data from multi-omic platforms to understand the functional relevance of these DMRs and refine DNAm association results by limiting phenotypic heterogeneity and clarifying if DNAm differences relate to the timing of onset, severity, duration of perinatal mental health outcomes of the current pregnancy or to previous history of depressive psychopathology.

An updated meta-analysis of the association between Toxoplasma gondii infection and risk of epilepsy

2019 ◽  
Vol 113 (8) ◽  
pp. 453-462 ◽  
Author(s):  
Maryam Sadeghi ◽  
Seyed Mohammad Riahi ◽  
Mona Mohammadi ◽  
Vafa Saber ◽  
Somayeh Aghamolaie ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Positive Association ◽  
Final Analysis ◽  
Toxoplasma Infection ◽  
Significant Positive Association ◽  
Worldwide Distribution ◽  
Subgroup Analyses ◽  
Toxoplasma Gondii Infection

Abstract Toxoplasma gondii is a neurotropic pathogen with worldwide distribution. To evaluate the association between Toxoplasma infection and the risk of epilepsy by meta-analysis, observational peer-reviewed studies were retrieved from PubMed, Embase, Web of Science, Scopus and Google Scholar (up to 10 October 2018) and by reference review. Pooled risk estimates were calculated using a random effects model. Heterogeneity was assessed using Cochrane’s Q-test and I2. In total, 16 eligible studies involving 19 data sets were included for the final analysis. A total 7897 participants (3771 epileptic patients, 4026 healthy controls) were included. The pooled odds ratio (OR) for Toxoplasma infection was increased to 1.72 (95% confidence interval [CI] 1.37 to 2.16) among patients with epilepsy. There was moderate heterogeneity among the studies (χ2=39.8, I2=62.3%, p=0.001). The ORs from subgroup analyses showed that both cryptogenic epilepsy (OR 2.65 [95% CI 1.91 to 3.68]) and active convulsive epilepsy (OR 1.37 [95% CI 1.09 to 1.72]) were significantly associated with Toxoplasma infection. Another subgroup analyses according to age showed a significant positive association in children (OR 1.33), adults (OR 1.57) and in all ages (OR 1.89). Our findings support the association between Toxoplasma infection and epilepsy. More prospective studies with larger sample sizes and more experimental studies are recommended to elucidate a causative relationship.

scholarly journals Does observability affect prosociality?

2018 ◽  
Vol 285 (1875) ◽  
pp. 20180116 ◽  
Author(s):  
Alex Bradley ◽  
Claire Lawrence ◽  
Eamonn Ferguson
Keyword(s):  
Confidence Interval ◽  
Boundary Conditions ◽  
Repeated Measures ◽  
Meta Analysis ◽  
Social Dilemmas ◽  
Positive Association ◽  
Practical Significance ◽  
Significant Positive Association ◽  
Theoretical Parameter ◽  
Moderator Analysis

The observation of behaviour is a key theoretical parameter underlying a number of models of prosociality. However, the empirical findings showing the effect of observability on prosociality are mixed. In this meta-analysis, we explore the boundary conditions that may account for this variability, by exploring key theoretical and methodological moderators of this link. We identified 117 papers yielding 134 study level effects (total n = 788 164) and found a small but statistically significant, positive association between observability and prosociality ( r = 0.141, 95% confidence interval = 0.106, 0.175). Moderator analysis showed that observability produced stronger effects on prosociality: (i) in the presence of passive observers (i.e. people whose role was to only observe participants) versus perceptions of being watched, (ii) when participants’ decisions were consequential (versus non-consequential), (iii) when the studies were performed in the laboratory (as opposed to in the field/online), (iv) when the studies used repeated measures (instead of single games), and (v) when the studies involved social dilemmas (instead of bargaining games). These effects show the conditions under which observability effects on prosociality will be maximally observed. We describe the theoretical and practical significance of these results.

T.N.3 A GENOME-WIDE DNA METHYLATION STUDY IN MONOZYGOTIC TWINS DISCORDANT FOR PRIMARY BILIARY CIRRHOSIS

2010 ◽  
Vol 42 ◽  
pp. S16
Author(s):  
A. Lleo ◽  
M.R. Martin ◽  
L. Zammataro ◽  
M.J. Mayo ◽  
N. Bach ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Primary Biliary Cirrhosis ◽  
Monozygotic Twins ◽  
Biliary Cirrhosis ◽  
Genome Wide ◽  
A Genome

scholarly journals Meta-Analysis of Genome-Wide Association Studies Identifies Novel Functional CpG-SNPs Associated with Bone Mineral Density at Lumbar Spine

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chuan Qiu ◽  
Hui Shen ◽  
Xiaoying Fu ◽  
Chao Xu ◽  
Hongwen Deng
Keyword(s):  
Bone Mineral Density ◽  
Dna Methylation ◽  
Lumbar Spine ◽  
Bone Mineral ◽  
Meta Analysis ◽  
Mineral Density ◽  
Significance Level ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

Osteoporosis is a serious public health issue, which is mostly characterized by low bone mineral density (BMD). To search for additional genetic susceptibility loci underlying BMD variation, an effective strategy is to focus on testing of specific variants with high potential of functional effects. Single nucleotide polymorphisms (SNPs) that introduce or disrupt CpG dinucleotides (CpG-SNPs) may alter DNA methylation levels and thus represent strong candidate functional variants. Here, we performed a targeted GWAS for 63,627 potential functional CpG-SNPs that may affect DNA methylation in bone-related cells, in five independent cohorts (n=5905). By meta-analysis, 9 CpG-SNPs achieved a genome-wide significance level (p<7.86×10−7) for association with lumbar spine BMD and additional 15 CpG-SNPs showed suggestive significant (p<5.00×10−5) association, of which 2 novel SNPs rs7231498 (NFATC1) and rs7455028 (ESR1) also reached a genome-wide significance level in the joint analysis. Several identified CpG-SNPs were mapped to genes that have not been reported for association with BMD in previous GWAS, such as NEK3 and NFATC1 genes, highlighting the enhanced power of targeted association analysis for identification of novel associations that were missed by traditional GWAS. Interestingly, several genomic regions, such as NEK3 and LRP5 regions, contained multiple significant/suggestive CpG-SNPs for lumbar spine BMD, suggesting that multiple neighboring CpG-SNPs may synergistically mediate the DNA methylation level and gene expression pattern of target genes. Furthermore, functional annotation analyses suggested a strong regulatory potential of the identified BMD-associated CpG-SNPs and a significant enrichment in biological processes associated with protein localization and protein signal transduction. Our results provided novel insights into the genetic basis of BMD variation and highlighted the close connections between genetic and epigenetic mechanisms of complex disease.

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