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

ACCESS DATA

Publications

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:BackgroundNumerous studies have indicated an obesity paradox in observational research on aging health, where being normal weight or underweight adversely affects cognitive function, while moderate obesity may offer protective benefits. This study aims to investigate the association between body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), and the joint effect of BMI and HC on cognitive impairment in older Chinese people.MethodsA total of 10,579 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this cross-sectional study. BMI, WC, HC, WHtR, WHR, and AVI were calculated from height, weight, WC, and HC measurements, where weight, WC, and HC were obtained by direct measurement. Mini-Mental State Examination was used to assess cognitive impairment. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using binary logistic regression. Non-linear correlations were investigated using restricted cubic spline curves.ResultsIn multivariate logistic regression models fully adjusted for confounding variables, our analyses showed significant negative associations of WC [OR 0.93 (95%CI 0.88-0.98), P = .012], HC [OR 0.92 (95%CI 0.87-0.97), P = .004], lower WHR (Q2) [OR 0.85 (95%CI 0.72-1.00), P = .044], and AVI [OR 0.93 (95%CI 0.88-0.98), P = .011] with cognitive impairment. Nonlinear curve analysis showed that the risk of cognitive impairment was lowest when the BMI was about 25.5 kg/m², suggesting that the optimal BMI for older Chinese people to maintain good cognitive ability may be in the overweight range. In addition, there was a non-linear "N" shaped relationship between HC and cognitive impairment, with HC having the highest risk of cognitive impairment at about 82 cm and the lowest risk at about 101 cm. The joint effects analysis indicated that the lowest risk was observed among those with normal or higher BMI but higher HC compared with participants with normal BMI levels and lower HC levels.ConclusionIn older Chinese people, a low-waisted and high-hip circumference body figure is favorable for cognitive function in older people. It also found a significant association between AVI and cognitive impairment. The joint analysis of BMI and HC suggests that maintaining a normal or higher BMI with a higher HC may be more conducive to maintaining good cognitive function.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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