Dataset Information

Body Mass Index Drives Changes in DNA Methylation: A Longitudinal Study.

ABSTRACT: RATIONALE:Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking. OBJECTIVE:To identify 5'-cytosine-phosphate-guanine-3' in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort. METHODS AND RESULTS:Race-specific EWASs were performed in 995 whites and 490 blacks from the Bogalusa Heart Study. Suggestive CpG sites were further replicated in 252 whites and 228 blacks from the Georgia Stress and Heart Study. Cross-lagged panel analysis was used to examine the temporal relationship between DNAm and BMI in 439 whites and 201 blacks who were examined twice 6.2 years apart. In discovery and replication samples, 349 CpG sites (266 novel) in whites and 36 (21 novel) in blacks were identified to be robustly associated with BMI, with 8 (1 novel) CpG sites overlapping between the 2 races. Cross-lagged panel analyses showed significant unidirectional paths (PFDR <0.05) from baseline BMI to follow-up DNAm at 18 CpG sites in whites and 7 in blacks; no CpG sites showed significant paths from DNAm at baseline to BMI at follow-up. Baseline BMI was associated with a DNAm score (calculated from DNAm levels at the associated CpG sites) at follow-up (P<0.001 both in blacks and in whites). CONCLUSIONS:The findings provide strong evidence that obesity is the cause, not a consequence, of changes in DNAm over time.

SUBMITTER: Sun D

PROVIDER: S-EPMC6786955 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Body Mass Index Drives Changes in DNA Methylation: A Longitudinal Study.

Sun Dianjianyi D Zhang Tao T Su Shaoyong S Hao Guang G Chen Tao T Li Quan-Zhen QZ Bazzano Lydia L He Jiang J Wang Xiaoling X Li Shengxu S Chen Wei W

Circulation research 20190912 9

<h4>Rationale</h4>Previous EWASs (Epigenome-Wide Association Studies) suggest that obesity may be the cause, not a consequence, of changes in DNA methylation (DNAm). However, longitudinal observations are lacking.<h4>Objective</h4>To identify 5'-cytosine-phosphate-guanine-3' in DNA (CpG) sites associated with body mass index (BMI) and examine the temporal relationship between dynamic changes in DNAm and BMI in a longitudinal cohort.<h4>Methods and results</h4>Race-specific EWASs were performed i ...[more]

PMID: 31510868

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Project description:Importance:While prenatal nutrition and maternal obesity are recognized as important contributors to epigenetic changes and childhood obesity, the role of paternal obesity in the epigenome of offspring has not been well studied. Objectives:To test whether periconception paternal body mass index (BMI) is associated with DNA methylation patterns in newborns, to examine associations between maternal and paternal BMI and the epigenome of offspring, and to examine persistence of epigenetic marks at ages 3 and 7 years. Design, Setting, and Participants:Project Viva is a prebirth cohort study of mothers and children including 2128 live births that enrolled mothers from April 1999 to July 2002 and followed offspring to adolescence. This study analyzed the subset of participants with available data on paternal BMI and DNA methylation in offspring blood in the newborn period, at age 3 years, and at age 7 years. Data were analyzed from July 2017 to October 2019. Exposures:The primary exposure was paternal periconception BMI; associations were adjusted for maternal prepregnancy BMI and stratified according to maternal BMI above or below 25. Main Outcomes and Measures:The primary outcome was genome-wide DNA methylation patterns in offspring blood collected at birth, age 3 years, and age 7 years. Results:A total of 429 father-mother-infant triads were included. The mean (SD) periconception paternal BMI was 26.4 (4.0) and mean maternal prepregnancy BMI was 24.5 (5.2); 268 fathers had BMI greater than or equal to 25 (mean [SD], 28.5 [3.3]) and 161 had BMI less than 25 (mean [SD], 22.8 [1.8]). Paternal BMI greater than or equal to 25 was associated with increased offspring birth weight compared with paternal BMI less than 25 (mean [SD] z score, 0.38 [0.91] vs 0.11 [0.96]; P?=?.004). Cord blood DNA methylation at 9 CpG sites was associated with paternal BMI independent of maternal BMI (q?<?.05). Methylation at cg04763273, between TFAP2C and BMP7, decreased by 5% in cord blood with every 1-unit increase in paternal BMI (P?=?3.13?×?10-8); hypomethylation at this site persisted at ages 3 years and 7 years. Paternal BMI was associated with methylation at cg01029450 in the promoter region of the ARFGAP3 gene; methylation at this site was also associated with lower infant birth weight (??=?-0.0003; SD?=?0.0001; P?=?.03) and with higher BMI z score at age 3 years. Conclusions and Relevance:In this study, paternal BMI was associated with DNA methylation, birth weight, and childhood BMI z score in offspring.

Project description:BACKGROUND:Prospective data are sparse for active commuting to work and body weight in Asia. We assessed the association of 5-year changes in commuting mode with body mass index (BMI) and the indicators of abdominal obesity in Japanese working adults. METHODS:In this longitudinal study, we studied 29,758 participants (25,808 men and 3950 women) in Japan aged 30 to 64 years at baseline who underwent further health examination 5 years after the baseline examination. Changes in BMI were calculated from objectively measured body height and weight at baseline and follow-up examination. Visceral and subcutaneous fat areas and waist circumference measured by computed tomography scans were used as indicators for abdominal adiposity. Linear regression was applied to estimate the association of changes in commuting mode with the obesity outcomes. RESULTS:Within the 5-year study period, adults who maintained inactive commuting gained weight, and compared with this group, adults who switched to inactive commuting had higher weight gain; conversely, adults who switched to active or public transportation commuting and especially those who maintained active or public transportation commuting experienced less weight gain. Subgroup analysis showed similar tendency across the different transitions of leisure-time exercise or occupational physical activity. For example, among adults who maintained no exercise (n = 16,087), the adjusted mean (95% confidence intervals) of the BMI change over 5 years in kg/m2 were 0.27 (0.24 to 0.30) for maintained inactive commuting group (reference), 0.34 (0.30 to 0.38) for switching to inactive commuting group (P = 0.046), 0.20 (0.18 to 0.22) for switching to active commuting or public transportation group (P = 0.001), and 0.09 (0.06 to 0.13) for maintained active commuting or public transportation group (P < 0.001). Maintained inactive commuting tended to be associated with larger gain in abdominal adiposity indicators. CONCLUSION:Switching from inactive commuting mode to more physically active commuting mode and maintaining active commuting can promote body weight control among working adults across different levels of occupational or leisure-time physical activity.

Project description:The aim of this retrospective study was to review body mass index (BMI) in a large cohort of Italian pediatric type 2 spinal muscular atrophy (SMA) patients, aged between 0 and 20 years and to establish possible differences in relation to a number of variables such as ventilation, motor function, and survival motor neuron 2 gene copies. Cross-sectional data were collected from 102 patients for a total of 344 visits. Standard growth charts for height and weight were used as reference, with age adjusted BMI calculated using the Center for Disease and Prevention Children's BMI Tool. In the 344 visits, weight ranged between 3.90 and 83 kg, and the BMI between 8.4 and 31.6 with a BMI/age z-scores < - 2SD present in 28% and BMI/age z-scores > + 2SD in 9% of the measurements. The BMI/age z-scores were relatively stable < 5 years of age with an increasing number of patients < - 2SD after the age of 5, and a wider range of BMI/age z-scores after the age of 13. A difference on the BMI/age z-scores was found among the different age subgroups (< 5, 5-12, ≥ 13 years). A multivariate analysis in 58 patients with longitudinal assessments showed that baseline BMI/age z-scores and gender were significantly contributing to the changes while other variables were not.ConclusionOur results confirm that careful surveillance of weight and BMI/age z-scores is needed in type 2 SMA. Further studies, including assessments of chewing and swallowing and of lean/fat body mass, will help to better understand the possible mechanisms underlying weight issues.What is known• Feeding difficulties have been reported in a few studies and were invariably found in patients with type 1 SMA. • Type 2 SMA patients often have low BMI with a relevant number of patients requiring tube feeding.What is new• Reduction in BMI/age z-score overtime appeared to depend on baseline BMI/age z-score and gender. • Patients with a low BMI/age z-score were at higher risk of developing further reduction.

Project description:BackgroundDNA 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 rather than a predictor. Future epigenome-wide association studies may benefit from further examining associations between early DNA methylation and later health outcomes.

Dataset Information

Body Mass Index Drives Changes in DNA Methylation: A Longitudinal Study.

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Body Mass Index Drives Changes in DNA Methylation: A Longitudinal Study.

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