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

Li, Shuai; Wong, Ee Ming; Bui, Minh; Nguyen, Tuong L.; Joo, Ji Hoon Eric; Stone, Jennifer; Dite, Gillian S.; Dugué, Pierre Antoine; Milne, Roger L.; Giles, Graham G.; Saffery, Richard; Southey, Melissa C.; Hopper, John L.

doi:10.1038/s41366-018-0103-4

Cited by 52 publications

(22 citation statements)

References 51 publications

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“…These new discoveries have important implications for understanding the causes of breast cancer. We have applied a new method for making inference about causation by examining familial confounding, called ICE FALCON [34], to data on twin pairs. We found no evidence that conventional DNA methylation in blood is having a causal effect on conventional mammographic density (Cumulus), or vice versa [35].…”

Section: Discussionmentioning

confidence: 99%

Going Beyond Conventional Mammographic Density to Discover Novel Mammogram-Based Predictors of Breast Cancer Risk

Hopper

Nguyen

Schmidt

et al. 2020

JCM

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This commentary is about predicting a woman’s breast cancer risk from her mammogram, building on the work of Wolfe, Boyd and Yaffe on mammographic density. We summarise our efforts at finding new mammogram-based risk predictors, and how they combine with the conventional mammographic density, in predicting risk for interval cancers and screen-detected breast cancers across different ages at diagnosis and for both Caucasian and Asian women. Using the OPERA (odds ratio per adjusted standard deviation) concept, in which the risk gradient is measured on an appropriate scale that takes into account other factors adjusted for by design or analysis, we show that our new mammogram-based measures are the strongest of all currently known breast cancer risk factors in terms of risk discrimination on a population-basis. We summarise our findings graphically using a path diagram in which conventional mammographic density predicts interval cancer due to its role in masking, while the new mammogram-based risk measures could have a causal effect on both interval and screen-detected breast cancer. We discuss attempts by others to pursue this line of investigation, the measurement challenge that allows different measures to be compared in an open and transparent manner on the same datasets, as well as the biological and public health consequences.

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Section: Discussionmentioning

confidence: 99%

Going Beyond Conventional Mammographic Density to Discover Novel Mammogram-Based Predictors of Breast Cancer Risk

Hopper

Nguyen

Schmidt

et al. 2020

JCM

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“…For sites affected by genetic factors, we used the methylation site heritability estimates found by van Dongen et al by analysing NTR data, 13 and the methylation quantitative trait locus (mQTL) results by Min et al 32 Loci associated with smoking or BMI included AHRR, F2RL3, 2q27.1, 6p21.33, HIF3A, SOCS3 and ABCG1. 3 , 4 , 5 , 6 , 7 , 8 …”

Section: Methodsmentioning

confidence: 99%

“… 1 , 2 DNA methylation, one of the most studied epigenetic modifications, has been found to be associated with several human traits and diseases, such as smoking 3 , 4 , 5 and obesity. 6 , 7 , 8 …”

Section: Introductionmentioning

confidence: 99%

Early life affects late-life health through determining DNA methylation across the lifespan: A twin study

Mather

et al. 2022

eBioMedicine

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“…The BMI classi cation results were found to be signi cantly associated with the presence of INS gene methylation before and after the intervention in the studied population. Previous epigenome studies have reported that there are CpG islands, approximately 500, which may be methylated in relation to the BMI [29], [30]. The causality between BMI and DNA methylation has been analyzed, suggesting that BMI and its change have a causal effect on DNA methylation [30].…”

Section: Resultsmentioning

confidence: 99%

Effect of inulin intervention on metabolic control and methylation of INS and IRS1 genes in patients with type 2 diabetes mellitus

Ramírez

Salazar-Piña

Cerón-Ramírez

et al. 2022

Preprint

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Background and Aims: Currently, treatments are being sought to improve the control of type II diabetes mellitus(T2DM), and agave inulin has been shown to be effective in reducing glucose levels and other metabolic control parameters. These effects on metabolic control may be associated with changes in the epigenetic modulation of genes of the insulin pathway. For the above mentioned the objective is determine the effect of agave inulin in biochemical parameters and metabolic control and observe the correlation with changes in INSand IRS1 genes methylation in T2DM patients. Methods: This was a longitudinal experimental study with 67 participants from Mexico, who received an intervention of inulin agave (10 g daily) for 2 months. Results: The parameters evaluated included anthropometric measurements, biochemical analyses, and the methylation levels of the INS and IRS1 genes by MSP-PCR. For the INS, it was methylated in 76.1% of participants before treatment, and it was methylated in 52.2% of participants after the intervention. For the IRS1, a hemimethylated status was present in 22.3% and 19.4% of the participants pre- and postintervention, respectively. We observed that there was a positive correlation between the changes in the methylation levels of the INS and IRS1 genes pre-and postintervention with metabolic control. For the INS, we found a negative and statistically significant correlation with abdominal fat. Conclusions: The present study demonstrated that intervention with agave inulin correlates with methylation changes of the IRS1 and INS genes and that genes methylation with the metabolic control in T2DM patients.

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

Abstract: For 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.

Cited by 52 publications

References 51 publications

Going Beyond Conventional Mammographic Density to Discover Novel Mammogram-Based Predictors of Breast Cancer Risk

Going Beyond Conventional Mammographic Density to Discover Novel Mammogram-Based Predictors of Breast Cancer Risk

Early life affects late-life health through determining DNA methylation across the lifespan: A twin study

Effect of inulin intervention on metabolic control and methylation of INS and IRS1 genes in patients with type 2 diabetes mellitus

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