RESUMEN
This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.
Asunto(s)
Epigénesis Genética , Epigenoma , Humanos , Femenino , Índice de Masa Corporal , Epigénesis Genética/genética , Obesidad/genética , HDL-Colesterol/genética , Estudio de Asociación del Genoma Completo , Metilación de ADN/genética , Epigenómica , Triglicéridos , Islas de CpG/genéticaRESUMEN
BACKGROUND: The prevalence of obesity is higher among populations in industrialized than in developing countries. OBJECTIVE: We sought to compare the relations of activity energy expenditure (AEE) with adiposity and weight change in 2 black populations with different levels of obesity. DESIGN: Total daily energy expenditure (TDEE) and resting energy expenditure (REE) were measured and AEE was calculated in 58 Nigerian and 34 US black women and men. Weight was remeasured after > or = 1 y in a subset of participants. AEE adjusted for body size and TDEE adjusted for REE were calculated with the use of the residual regression method. The cross-sectional relations between percentage body fat and activity were modeled by using regression analysis, and longitudinal relations between weight change and adjusted energy expenditure variables were calculated. RESULTS: Women and men from the United States weighed more, had more body fat, and had higher levels of TDEE, REE, and AEE than did those from Nigeria. Cross-sectionally, AEE was negatively associated with adiposity after adjustment for body size and age (P < 0.001), regardless of site. Between 60% and 80% of the variance in adiposity was explained by AEE or TDEE. REE, AEE, and TDEE adjusted for body size and age were negatively correlated with weight change among Nigerian women but not men. CONCLUSIONS: The significant difference observed in mean adiposity between Nigerians and US blacks was not explained by differences in AEE. However, a low AEE was an important determinant of high percentages of body fat in black adults and was associated with increased weight gain in Nigerian women.