scholarly journals Paternal body mass index and offspring DNA methylation: findings from the PACE consortium

2020 ◽  
Author(s):  
Gemma C Sharp ◽  
Rossella Alfano ◽  
Akram Ghantous ◽  
Jose Urquiza ◽  
Sheryl L Rifas-Shiman ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Health Outcomes ◽  
Candidate Gene ◽  
Body Mass ◽  
Association Studies ◽  
Meta Analysis ◽  
450K Array ◽  
Total N ◽  
Candidate Gene Studies

AbstractBackgroundAccumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.Methods and findingsIn the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.ConclusionOur findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.Author SummaryPrevious small, mostly candidate gene studies have shown associations between paternal pre-pregnancy BMI and offspring blood DNA methylation. However, in our large meta-analysis of co-ordinated EWAS results from a total of 19 datasets across two timepoints, we found little evidence to support these findings, even at imprinted regions. This does not rule out the possibility of a paternal epigenetic effect in different tissues, at regions not covered by the 450k array, via different mechanisms, or in populations with greater extremes of paternal BMI. More research is warranted to help understand the size and nature of contributions of paternal adiposity to offspring epigenetics and health outcomes.

scholarly journals Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry

2018 ◽  
Vol 27 (20) ◽  
pp. 3641-3649 ◽  
Author(s):  
Loic Yengo ◽  
Julia Sidorenko ◽  
Kathryn E Kemper ◽  
Zhili Zheng ◽  
Andrew R Wood ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals The association of DNA methylation with body mass index: distinguishing between predictors and biomarkers

2019 ◽  
Author(s):  
Zoe E. Reed ◽  
Matthew J. Suderman ◽  
Caroline L. Relton ◽  
Oliver S.P. Davis ◽  
Gibran Hemani
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Association Studies ◽  
Predictive Ability ◽  
Mendelian Randomisation ◽  
Multiple Time ◽  
Adult Women ◽  
Genetic Score ◽  
Cardiometabolic Traits

AbstractBackgroundDNA methylation is associated with body mass index (BMI), but it is not clear if methylation scores are biomarkers for extant BMI, or predictive of future BMI. Here we explore the causal nature and predictive utility of DNA methylation measured in peripheral blood with BMI and cardiometabolic traits.MethodsAnalyses were conducted across the life course using the ARIES cohort of mothers (n=792) and children (n=906), for whom DNA methylation and genetic profiles and BMI at multiple time points (3 in children at birth, in childhood and in adolescence, 2 in mothers during pregnancy and in middle age) were available. Genetic and DNA methylation scores for BMI were derived using published associations between BMI and DNA methylation and genotype. Causal relationships between methylation and BMI were assessed using Mendelian randomisation and cross-lagged models.ResultsThe DNA methylation scores in adult women explained 10% of extant BMI variance. However, less extant variance was explained by scores generated in the same women during pregnancy (2% BMI variance) and in older children (15-17 years; 3% BMI variance). Similarly, little extant variance was explained in younger children (at birth and at 7 years; 1% and 2%, respectively). These associations remained following adjustment for smoking exposure and education levels. The DNA methylation score was found to be a poor predictor of future BMI using linear and cross-lagged models, suggesting that DNA methylation variation does not cause later variation in BMI. However, there was some evidence to suggest that BMI is predictive of later DNA methylation. Mendelian randomisation analyses also support this direction of effect, although evidence is weak. Finally, we find that DNA methylation scores for BMI are associated with extant cardiometabolic traits independently of BMI and genetic score.ConclusionThe age-specific nature of DNA methylation associations with BMI, lack of causal relationship, and limited predictive ability of future BMI, indicate that DNA methylation is likely influenced by BMI and might more accurately be considered a biomarker of BMI and related outcomes than a predictor. Future epigenome-wide association studies may benefit from further examining associations between early DNA methylation and later health outcomes.

scholarly journals Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Anne K. Bozack ◽  
Philippe Boileau ◽  
Linqing Wei ◽  
Alan E. Hubbard ◽  
Fenna C. M. Sillé ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Data Processing ◽  
Association Studies ◽  
Meta Analysis ◽  
Arsenic Exposure ◽  
Health Concern ◽  
Global Public Health ◽  
Buccal Cells ◽  
450K Array ◽  
Variable Regions

Abstract Background Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. Methods DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. Results In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. Conclusions Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.

A novel locus for body mass index on 5p15.2: A meta-analysis of two genome-wide association studies

Gene ◽  
2012 ◽  
Vol 500 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Ke-Sheng Wang ◽  
Xuefeng Liu ◽  
Shimin Zheng ◽  
Min Zeng ◽  
Yue Pan ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

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

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Florianne O. L. Vehmeijer ◽  
Leanne K. Küpers ◽  
Gemma C. Sharp ◽  
Lucas A. Salas ◽  
Samantha Lent ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Association Studies ◽  
Standard Deviation Score ◽  
Correlation Coefficients ◽  
Childhood And Adolescence ◽  
Cross Sectional ◽  
Meta Analyses ◽  
Age Range

Abstract 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 × 10−7, 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 Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7). 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.

scholarly journals Meta-analysis of genome-wide association studies for height and body mass index in ∼700,000 individuals of European ancestry

2018 ◽  
Author(s):  
Loic Yengo ◽  
Julia Sidorenko ◽  
Kathryn E. Kemper ◽  
Zhili Zheng ◽  
Andrew R. Wood ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Summary Statistics ◽  
Genome Wide ◽  
Independent Snps

Genome-wide association studies (GWAS) stand as powerful experimental designs for identifying DNA variants associated with complex traits and diseases. In the past decade, both the number of such studies and their sample sizes have increased dramatically. Recent GWAS of height and body mass index (BMI) in ∼250,000 European participants have led to the discovery of ∼700 and ∼100 nearly independent SNPs associated with these traits, respectively. Here we combine summary statistics from those two studies with GWAS of height and BMI performed in ∼450,000 UK Biobank participants of European ancestry. Overall, our combined GWAS meta-analysis reaches N∼700,000 individuals and substantially increases the number of GWAS signals associated with these traits. We identified 3,290 and 716 near-independent SNPs associated with height and BMI, respectively (at a revised genome-wide significance threshold of p<1 × 10−8), including 1,185 height-associated SNPs and 554 BMI-associated SNPs located within loci not previously identified by these two GWAS. The genome-wide significant SNPs explain ∼24.6% of the variance of height and ∼5% of the variance of BMI in an independent sample from the Health and Retirement Study (HRS). Correlations between polygenic scores based upon these SNPs with actual height and BMI in HRS participants were 0.44 and 0.20, respectively. From analyses of integrating GWAS and eQTL data by Summary-data based Mendelian Randomization (SMR), we identified an enrichment of eQTLs amongst lead height and BMI signals, prioritisting 684 and 134 genes, respectively. Our study demonstrates that, as previously predicted, increasing GWAS sample sizes continues to deliver, by discovery of new loci, increasing prediction accuracy and providing additional data to achieve deeper insight into complex trait biology. All summary statistics are made available for follow up studies.

Sign in / Sign up

Export Citation Format

Share Document