Novel associations between blood DNA methylation and body mass index in middle-aged and older adults

Geurts, Y.M.; Dugué, Pierre Antoine; Joo, Jihoon E.; Makalic, Enes; Jung, Chol‐Hee; Guan, Weihua; Nguyen, Steve; Grove, Megan L.; Wong, Ee Ming; Hodge, Allison; Bassett, Julie K.; FitzGerald, Liesel M.; Tsimiklis, Helen; Baglietto, Laura; Severi, Gianluca; Schmidt, Daniel F.; Buchanan, Daniel D.; MacInnis, Robert J.; Hopper, John L.; Pankow, James S.; Demerath, Ellen W.; Southey, Melissa C.; Giles, Graham G.; English, Dallas R.; Milne, Roger L.

doi:10.1038/ijo.2017.269

Cited by 65 publications

(105 citation statements)

References 54 publications

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“…cg21429551 and cg19390658 map to GARS , which encodes the ligase glycyl-tRNA synthetase. These CpGs were associated with smoking, BMI, triglycerides and HDL-C levels in our study and in previous reports [36,49,50]. Two previous candidate gene studies including both CpGs or cg21429551 alone have shown negative results regarding their association with CHD [32,36].…”

Section: Discussionsupporting

confidence: 76%

DNA Methylation Biomarkers Of Myocardial Infarction And Cardiovascular Disease

Fernández‐Sanlés

Sayols-Baixeras

Subirana

et al. 2019

Preprint

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ObjectiveTo assess the association between DNA methylation and acute myocardial infarction, the predictive added value of the identified methylation marks, and the causality of those associations.Approach and ResultsWe conducted a case-control, two-stage, epigenome-wide association study on acute myocardial infarction (ndiscovery=391, nvalidation=204). DNA methylation was assessed using the Infinium MethylationEPIC BeadChip (over 850,000 CpGs). DNA methylation was the exposure variable and myocardial infarction the outcome of interest. After a fixed-effects meta-analysis, 34 CpGs fulfilled Bonferroni significance. These findings were also analysed in two independent cohort studies (n∼1,800 and n∼2,500) with incident coronary (CHD) and cardiovascular disease (CVD). The Infinium HumanMethylation450 BeadChip was used in these two studies (over 480,000 CpGs) and only 12 of the 34 CpGs were available in those samples. Finally, we validated four of them in association with incident CHD: AHRR-mapping cg05575921, PTCD2-mapping cg25769469, intergenic cg21566642 and MPO-mapping cg04988978. The four CpGs were also associated with classical cardiovascular risk factors. A methylation risk score based on those CpGs did not improve the predictive capacity of the Framingham risk function. To assess the causal effects of those CpGs we performed Mendelian randomization analysis but only one metQTL could be identified and the results were not conclusive.ConclusionsWe have identified 34 CpGs related to acute myocardial infarction. These loci highlight the relevance of smoking, lipid metabolism, and inflammation in the biological mechanisms related to myocardial infarction. Four were additionally associated with incident CHD and CVD but did not provide additional predictive information.

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Section: Discussionsupporting

confidence: 76%

DNA Methylation Biomarkers Of Myocardial Infarction And Cardiovascular Disease

Fernández‐Sanlés

Sayols-Baixeras

Subirana

et al. 2019

Preprint

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“…We performed EWASs between BMI at two life points and blood DNA methylation, and found that methylation at several loci was associated with BMI at middle age, BMI at age 18-21 years and BMI change. Methylation at some of these loci, ZPLD1 10, 14 , SOCS3 12-16 , CRELD2 10, 13, 14 , NOD2 13, 14, 16 and PHGDH 9,13,14,16 , has been previously reported to be associated with BMI. Associations at the other loci, such as LY9, COL6A2, ZBBX, MAP3K13, CRH, etc., do not appear to have been previously reported.…”

Section: Discussionmentioning

confidence: 98%

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

Wong

Bui

et al. 2017

Preprint

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“…For the AMDTSS, the model was additionally adjusted for family and zygosity as random effects. For the MCCS, the model was additionally adjusted for sample type (dried blood spots/mononuclear cells/buffy coats) and country of birth (Australia/UK/Italy/Greece) as fixed effects, and for study, plate and chip as random effects . For the AMDTSS, the Bioconductor package bacon was used to adjust for the observed inflation of test statistics.…”

Section: Methodsmentioning

confidence: 99%

Genome‐wide association study of peripheral blood DNA methylation and conventional mammographic density measures

Dugué

Baglietto

et al. 2019

Intl Journal of Cancer

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Age‐ and body mass index (BMI)‐adjusted mammographic density is one of the strongest breast cancer risk factors. DNA methylation is a molecular mechanism that could underlie inter‐individual variation in mammographic density. We aimed to investigate the association between breast cancer risk‐predicting mammographic density measures and blood DNA methylation. For 436 women from the Australian Mammographic Density Twins and Sisters Study and 591 women from the Melbourne Collaborative Cohort Study, mammographic density (dense area, nondense area and percentage dense area) defined by the conventional brightness threshold was measured using the CUMULUS software, and peripheral blood DNA methylation was measured using the HumanMethylation450 (HM450) BeadChip assay. Associations between DNA methylation at >400,000 sites and mammographic density measures adjusted for age and BMI were assessed within each cohort and pooled using fixed‐effect meta‐analysis. Associations with methylation at genetic loci known to be associated with mammographic density were also examined. We found no genome‐wide significant (p < 10−7) association for any mammographic density measure from the meta‐analysis, or from the cohort‐specific analyses. None of the 299 methylation sites located at genetic loci associated with mammographic density was associated with any mammographic density measure after adjusting for multiple testing (all p > 0.05/299 = 1.7 × 10−4). In summary, our study did not find evidence for associations between blood DNA methylation, as measured by the HM450 assay, and conventional mammographic density measures that predict breast cancer risk.

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Novel associations between blood DNA methylation and body mass index in middle-aged and older adults

Cited by 65 publications

References 54 publications

DNA Methylation Biomarkers Of Myocardial Infarction And Cardiovascular Disease

DNA Methylation Biomarkers Of Myocardial Infarction And Cardiovascular Disease

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

Genome‐wide association study of peripheral blood DNA methylation and conventional mammographic density measures

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