Genetic Effects on DNA Methylation and Its Potential Relevance for Obesity in Mexican Americans

Abstract

Several studies have identified effects of genetic variation on DNA methylation patterns and associated heritability, with research primarily focused on Caucasian individuals. In this paper, we examine the evidence for genetic effects on DNA methylation in a Mexican American cohort, a population burdened by a high prevalence of obesity. Using an Illumina-based platform and following stringent quality control procedures, we assessed a total of 395 CpG sites in peripheral blood samples obtained from 183 Mexican American individuals for evidence of heritability, proximal genetic regulation and association with age, sex and obesity measures (i.e. waist circumference and body mass index). We identified 16 CpG sites (∼4%) that were significantly heritable after Bonferroni correction for multiple testing and 27 CpG sites (∼6.9%) that showed evidence of genetic effects. Six CpG sites (∼2%) were associated with age, primarily exhibiting positive relationships, including CpG sites in two genes that have been implicated in previous genome-wide methylation studies of age (FZD9 and MYOD1). In addition, we identified significant associations between three CpG sites (∼1%) and sex, including DNA methylation in CASP6, a gene that may respond to estradiol treatment, and in HSD17B12, which encodes a sex steroid hormone. Although we did not identify any significant associations between DNA methylation and the obesity measures, several nominally significant results were observed in genes related to adipogenesis, obesity, energy homeostasis and glucose homeostasis (ARHGAP9, CDKN2A, FRZB, HOXA5, JAK3, MEST, NPY, PEG3 and SMARCB1). In conclusion, we were able to replicate several findings from previous studies in our Mexican American cohort, supporting an important role for genetic effects on DNA methylation. In addition, we found a significant influence of age and sex on DNA methylation, and report on trend-level, novel associations between DNA methylation and measures of obesity.

The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

“…This model is supported by our EMSA data demonstrating impaired SOX6 binding to a MEST promoter template with adjacent CpG methylation. Our findings therefore extend published observations that obesity significantly associates with decreased methylation levels at the MEST gene (Soubry et al, 2015), that MEST hypomethylation is linked to metabolic programming in offspring with a background in gestational diabetes (El Hajj et al, 2013), and that there is an inverse relationship between MEST CpG methylation levels and body composition measures, such as waist circumference and body mass index (Carless et al, 2013).…”

Low Oxygen Consumption is Related to a Hypomethylation and an Increased Secretion of IL-6 in Obese Subjects with Sleep Apnea-Hypopnea Syndrome

“…Nevertheless, information in cancer-free populations with metabolic diseases is much more limited, with the added issue of race and gender differences [21]. Emerging evidence suggests that gene-specific DNA methylation in blood cells may play an important role in obesity etiology [12,19,22,23,24,25,26]. Recently, epigenetic wide-association studies have demonstrated a strong association between body mass index (BMI) and DNA methylation in multiple loci [27,28].…”

Association Between BMI and DNA Methylation in Blood or Normal Adult Breast Tissue: A Systematic Review

“…Twenty studies included breast cancer-free individuals. Of these, two included only women (13, 25), 16 included both men and women (24,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), one was a meta-analysis of three cohorts (KORA, LOLIPOP, EPICOR) (41) and another a meta-analysis of two cohorts (FHS, LBC) (42). Three studies had mixed breast cancer patients and breast cancer-free Discovery sample column: *n not obese/n obese; # Data from meta-analysis are combined; ˚Mean between women's data and men's data; NW stands for normal weight, OW for overweight, OB for obese and V for visit.…”