Dataset Information

Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.

ABSTRACT: OBJECTIVE:To conduct an epigenome-wide analysis of DNA methylation and obesity traits. METHODS:DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family structure, was modeled. RESULTS:Epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (n?=?2,377) and the Atherosclerosis Risk in Communities study (n?=?2,097), were found. Top findings were in CPT1A (meta-analysis P?=?2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P?=?2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P?=?6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P?=?2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity. CONCLUSIONS:This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.

SUBMITTER: Aslibekyan S

PROVIDER: S-EPMC4482015 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.

Aslibekyan Stella S Demerath Ellen W EW Mendelson Michael M Zhi Degui D Guan Weihua W Liang Liming L Sha Jin J Pankow James S JS Liu Chunyu C Irvin Marguerite R MR Fornage Myriam M Hidalgo Bertha B Lin Li-An LA Thibeault Krista Stanton KS Bressler Jan J Tsai Michael Y MY Grove Megan L ML Hopkins Paul N PN Boerwinkle Eric E Borecki Ingrid B IB Ordovas Jose M JM Levy Daniel D Tiwari Hemant K HK Absher Devin M DM Arnett Donna K DK

Obesity (Silver Spring, Md.) 20150701 7

<h4>Objective</h4>To conduct an epigenome-wide analysis of DNA methylation and obesity traits.<h4>Methods</h4>DNA methylation was quantified in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T-cell purity, smoking, and family str ...[more]

PMID: 26110892

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Project description:ObjectiveObesity is the prominent modifiable risk factor known to influence the occurrence and progression of diabetes other than age, and the objective of this study was to evaluate and compare the predictive value of three simple baseline anthropometric indicators of obesity, body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR), for the occurrence of diabetes at different time points in the future.MethodsThe study subjects were 12,823 individuals with normoglycemic at baseline who underwent health screening and had measurements of BMI, WC, and WHtR. The outcome of interest was new-onset diabetes during follow-up. Time-dependent receiver operator characteristics (ROC) curves of baseline BMI, WC, and WHtR for predicting the risk of diabetes in the next 2 to 12 years were constructed and their area under the ROC curves (AUCs) and corresponding optimal threshold values were calculated for each time point, which were used to compare the accuracy and stability of the above three indicators for predicting the occurrence of diabetes in different future periods.ResultsDuring a median follow-up period of 7.02 years, with a maximum follow-up of 13 years, 320 new-onset diabetes were recorded. After adjusting for confounders and comparing standardized hazard ratios (HRs), WC was shown to be the best simple anthropometric indicator of obesity reflecting diabetes risk in all models, followed by WHtR. Time-dependent ROC analysis showed that WC had the highest AUC in predicting the occurrence of diabetes in the short term (2-5 years), and WHtR had the highest AUC in predicting the occurrence of diabetes in the medium to long term (6-12 years), while in any time point, both WC and WHtR had higher AUC than BMI in predicting future diabetes. In addition, we found relatively larger fluctuations in the thresholds of BMI and WC for predicting diabetes over time, while the thresholds of WHtR consistently remained between 0.47-0.50; comparatively speaking, WHtR may have greater application value in predicting future diabetes.ConclusionsOur analysis sustained that central obesity is a more important predictor of diabetes, and in clinical practice, we proposed measuring WHtR as a useful tool for predicting future diabetes.

Project description:PURPOSE:Recent studies have suggested height as a risk factor for glioma, but less is known regarding body mass index (BMI) or other anthropomorphic measures. We evaluated the association between body habitus and risk of glioma. METHODS:We evaluated the association of measures of height, BMI, waist circumference, and somatotypes with risk of glioma in two prospective cohorts, the Nurses' Health Study and the Health Professionals Follow-Up Study. RESULTS:We documented 508 incident cases of glioma (321 glioblastoma [GBM]). In both cohorts, we found no significant association between adult BMI or waist circumference and risk of glioma, with pooled HR for BMI of 1.08 (95% CI 0.85-1.38 comparing???30 to <?25 kg/m2) and for waist circumference of 1.05 (95% CI 0.80-1.37 highest vs. lowest quintile). Higher young adult BMI (at age 18 in NHS and 21 in HPFS) was associated with modestly increased risk of glioma in the pooled cohorts (pooled HR 1.35, 95% CI 1.06-1.72 comparing???25 kg/m2 vs. less; HR 1.34 for women and 1.37 for men). Analysis of body somatotypes suggested reduced risk of glioma among women with heavier body types at all ages this measure was assessed (HRs ranging from 0.52 to 0.65 comparing highest tertile to lowest tertile), but no significant association among men. Height was associated with increased risk of glioma among women (HR?1.09, 95% CI 1.04-1.14 per inch), but not significantly among men. Within the 8 years prior to diagnosis, cases had no material weight loss compared to non-cases. All results were similar when limited to GBM. CONCLUSION:Adult BMI and waist circumference were not associated with glioma. Higher BMI at age 21 for men and at age 18 for women was modestly associated with risk in the pooled cohort. Based on body somatotypes, however, women with heavier body types during childhood and young adulthood may be at lower risk of glioma, although this association was not observed later in life with measurements of BMI. Greater height was associated with increased risk, and the trend was more pronounced in women.

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Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.

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Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference.

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