scholarly journals Inference about causation between body mass index and DNA methylation in blood from a twin family study

2017 ◽  
Author(s):  
Shuai Li ◽  
Ee Ming Wong ◽  
Minh Bui ◽  
Tuong L Nguyen ◽  
Ji-Hoon Eric Joo ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Causal Effect ◽  
False Discovery ◽  
Average Methylation ◽  
Twin Families ◽  
Genomic Locations

AbstractBackgroundSeveral studies have reported DNA methylation in blood to be associated with body mass index (BMI), but only a few have investigated causal aspects of the association. We used a twin family design to assess this association at two life points and applied a novel analytical approach to investigate the evidence for causality.MethodsThe methylation profile of DNA from peripheral blood was measured for 479 Australian women (mean age 56 years) from 130 twin families. Linear regression was used to estimate the associations of methylation at ~410 000 cytosine-guanine dinucleotides (CpG), and of the average methylation at ~20 000 genes, with current BMI, BMI at age 18-21 years, and the change between the two (BMI change). A novel regression-based methodology for twins, Inference about Causation through Examination of Familial Confounding (ICE FALCON), was used to assess causation.ResultsAt 5% false discovery rate, nine, six and 12 CpGs at 24 loci were associated with current BMI, BMI at age 18-21 years and BMI change, respectively. The average methylation of BHLHE40 and SOCS3 loci was associated with current BMI, and of PHGDH locus was associated with BMI change. From the ICE FALCON analyses with BMI as the predictor and methylation as the outcome, a woman’s methylation level was associated with her co-twin’s BMI, and the association disappeared conditioning on her own BMI, consistent with BMI causing methylation. To the contrary, using methylation as the predictor and BMI as the outcome, a woman’s BMI was not associated with her co-twin’s methylation level, consistent with methylation not causing BMI.ConclusionFor middle-aged women, peripheral blood DNA methylation at several genomic locations is associated with current BMI, BMI at age 18-21 years and BMI change. Our study suggests that BMI has a causal effect on peripheral blood DNA methylation.

scholarly journals The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study

2018 ◽  
Author(s):  
Amy E. Taylor ◽  
Rebecca C. Richmond ◽  
Teemu Palviainen ◽  
Anu Loukola ◽  
Jaakko Kaprio ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Bidirectional Association ◽  
Metabolite Ratio ◽  
Nicotine Metabolite Ratio

AbstractBackgroundGiven clear evidence that smoking lowers weight, it is possible that individuals with higher body mass index (BMI) smoke in order to lose or maintain their weight.Methods and FindingsWe undertook Mendelian randomization analyses using 97 genetic variants associated with BMI. We performed two sample Mendelian randomization analyses of the effects of BMI on smoking behaviour in UK Biobank (N=335,921) and the Tobacco and Genetics consortium genomewide association study (GWAS) (N≤74,035) respectively, and two sample Mendelian randomization analyses of the effects of BMI on cotinine levels (N≤4,548) and nicotine metabolite ratio (N≤1,518) in published GWAS, and smoking-related DNA methylation in the Avon Longitudinal Study of Parents and Children (N≤846).In inverse variance weighted Mendelian randomization analysis, there was evidence that higher BMI was causally associated with smoking initiation (OR for ever vs never smoking per one SD increase in BMI: 1.19, 95% CI: 1.11 to 1.27) and smoking heaviness (1.45 additional cigarettes smoked per day per SD increase in BMI, 95% CI: 1.03 to 1.86), but little evidence for a causal effect with smoking cessation. Results were broadly similar using pleiotropy robust methods (MR-Egger, median and weighted mode regression). These results were supported by evidence for a causal effect of BMI on DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus. There was no strong evidence that BMI was causally associated with cotinine, but suggestive evidence for a causal negative association with the nicotine metabolite ratio.ConclusionsThere is a causal bidirectional association between BMI and smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism. It may be useful to consider BMI and smoking together when designing prevention strategies to minimise the effects of these risk factors on health outcomes.

scholarly journals The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giuliana Favara ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
The Relationship

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

scholarly journals Association between the extent of DNA methylation at the CpG sites of HIF3A and parameters of obesity in the general Japanese population

2020 ◽  
Author(s):  
Genki Mizuno ◽  
Hiroya Yamada ◽  
Eiji Munetsuna ◽  
Mirai Yamazaki ◽  
Yoshitaka Ando ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Methylation Level ◽  
Japanese Population ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Transcriptional Responses ◽  
General Japanese Population ◽  
Cpg Sites

AbstractObesity is a major public health problem worldwide owing to the substantial increase in risk of metabolic diseases. Hypoxia-inducible factors (HIFs) regulate transcriptional responses to hypoxic stress. DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index in the whole blood and adipose tissue. This study investigates the correlation between DNA methylation of HIF3A and parameters of obesity, including thickness of visceral (VAT) and subcutaneous adipose tissues, in the general Japanese population. Participants (220 men and 253 women) who underwent medical examination were enrolled in this cross-sectional study. We used pyrosequencing to quantify DNA methylation (CpG sites of cg16672562, cg22891070, and cg27146050) in HIF3A. DNA methylation of HIF3A was only different in women. Multiple regression analysis showed that DNA methylation level at cg27146050 was associated with thickness of VAT in women. DNA methylation level at cg27146050 also correlated with body mass index and percentage of body fat in women after excluding smokers and non-smokers who quit smoking with the last 5 years. DNA methylation in the CpG site (cg27146050) of HIF3A correlated with parameters of obesity in Japanese women.

scholarly journals The effect of eligibility for antiretroviral therapy on body mass index and blood pressure in KwaZulu-Natal, South Africa

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aditi Kuber ◽  
Anna Reuter ◽  
Pascal Geldsetzer ◽  
Natsayi Chimbindi ◽  
Mosa Moshabela ◽  
...  
Keyword(s):  
South Africa ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Antiretroviral Therapy ◽  
Body Mass ◽  
Treatment Guidelines ◽  
Causal Effect ◽  
Regression Discontinuity Design ◽  
National Treatment ◽  
Kwazulu Natal

AbstractWe use a regression discontinuity design to estimate the causal effect of antiretroviral therapy (ART) eligibility according to national treatment guidelines of South Africa on two risk factors for cardiovascular disease, body mass index (BMI) and blood pressure. We combine survey data collected in 2010 in KwaZulu-Natal, South Africa, with clinical data on ART. We find that early ART eligibility significantly reduces systolic and diastolic blood pressure. We do not find any significant effects on BMI. The effect on blood pressure can be detected up to three years after becoming eligible for ART.

Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter

Endocrine ◽  
2009 ◽  
Vol 35 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Sofia Movérare-Skrtic ◽  
Dan Mellström ◽  
Liesbeth Vandenput ◽  
Mathias Ehrich ◽  
Claes Ohlsson
Keyword(s):  
Body Mass Index ◽  
Androgen Receptor ◽  
Body Mass ◽  
Peripheral Blood ◽  
Peripheral Blood Leukocyte ◽  
Methylation Pattern ◽  
Blood Leukocyte

Abstract MP32: Epigenome-Wide DNA Methylation Profiling in a CVD Cohort: The ARIC Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
James S Pankow ◽  
Ellen W Demerath ◽  
Weihua Guan ◽  
Myriam Fornage ◽  
Thomas H Mosley ◽  
...  
Keyword(s):  
Dna Methylation ◽  
X Chromosome ◽  
Methylation Level ◽  
Association Studies ◽  
Univariate Analysis ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Stage Of Development ◽  
Average Methylation ◽  
Aric Study

DNA methylation is mitotically heritable modification in chromatin structure that impacts transcriptional control of genes and cellular function. Recent technological advances provide opportunities to systematically interrogate variation in DNA methylation across the genome in large epidemiologic studies. However, unlike inherited changes to the genetic sequence, variation in site-specific methylation varies by tissue, stage of development, disease state, and may be affected by gender, aging and exposure to environmental factors. As a result, there is likely a greater threat of confounding in epigenome-wide methylation studies compared to genome-wide association studies of SNPs. The Illumina Infinium HumanMethylation450 BeadChip was used to measure DNA methylation in peripheral blood obtained from African American participants from the Jackson, Mississippi and Forsyth County, North Carolina field centers of the Atherosclerosis Risk in Communities (ARIC) Study, a population-based cohort of middle-aged men and women. After excluding outlier samples and CpG sites using quality control filters, we analyzed 473,687 sites in 2873 subjects who were between 47-71 years of age at the time of DNA collection. We used linear regression with robust standard errors to examine cross-sectional associations of demographic factors with the beta value, an estimate of the average methylation level at each locus, and applied a Bonferroni correction to account for multiple testing. In univariate analysis, 91% of sites on the X chromosome and 10% of sites on the autosomes exhibited statistically significant gender differences in methylation level (p<1x10-7). Average methylation was higher in women than men for most of the significant sites (63% and 89% on the X chromosome and autosomes, respectively). Percent European ancestry estimated from ancestry informative markers was significantly associated with methylation level at 4% of sites. Age was also significantly associated with methylation at 4% of sites; average methylation was lower in older subjects compared to younger subjects for the majority (58%) of these sites. As we begin to implement epigenome-wide studies of DNA methylation and CVD outcomes, these results indicate that such studies will require careful consideration of adjustment techniques to avoid confounding by gender, age, and other covariates.

scholarly journals DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence

Epigenetics ◽  
2018 ◽  
Vol 13 (10-11) ◽  
pp. 1072-1087 ◽  
Author(s):  
Jian V. Huang ◽  
Andres Cardenas ◽  
Elena Colicino ◽  
C. Mary Schooling ◽  
Sheryl L. Rifas-Shiman ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Risk Score ◽  
Early Adolescence ◽  
Metabolic Risk ◽  
Childhood Body Mass Index ◽  
Metabolic Risk Score

scholarly journals Application of Mendelian Randomization to Investigate the Association of Body Mass Index with Health Care Costs

2020 ◽  
Vol 40 (2) ◽  
pp. 156-169 ◽  
Author(s):  
Christoph F. Kurz ◽  
Michael Laxy
Keyword(s):  
Health Care ◽  
Body Mass Index ◽  
Body Mass ◽  
Health Care Costs ◽  
Instrumental Variables ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Omitted Variables ◽  
Care Costs ◽  
Genetic Instruments

Causal effect estimates for the association of obesity with health care costs can be biased by reversed causation and omitted variables. In this study, we use genetic variants as instrumental variables to overcome these limitations, a method that is often called Mendelian randomization (MR). We describe the assumptions, available methods, and potential pitfalls of using genetic information and how to address them. We estimate the effect of body mass index (BMI) on total health care costs using data from a German observational study and from published large-scale data. In a meta-analysis of several MR approaches, we find that models using genetic instruments identify additional annual costs of €280 for a 1-unit increase in BMI. This is more than 3 times higher than estimates from linear regression without instrumental variables (€75). We found little evidence of a nonlinear relationship between BMI and health care costs. Our results suggest that the use of genetic instruments can be a powerful tool for estimating causal effects in health economic evaluation that might be superior to other types of instruments where there is a strong association with a modifiable risk factor.

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