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Genetic effects on DNA methylation and its potential relevance for obesity in Mexican Americans.
- Source :
-
PloS one [PLoS One] 2013 Sep 13; Vol. 8 (9), pp. e73950. Date of Electronic Publication: 2013 Sep 13 (Print Publication: 2013). - Publication Year :
- 2013
-
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.
- Subjects :
- 17-Hydroxysteroid Dehydrogenases metabolism
Age Factors
Body Mass Index
Caspase 6 metabolism
CpG Islands
Female
Gene Expression Regulation
Genetic Variation
Genome-Wide Association Study
Humans
Inheritance Patterns
Male
Middle Aged
Obesity metabolism
Obesity physiopathology
Sex Factors
17-Hydroxysteroid Dehydrogenases genetics
Caspase 6 genetics
DNA Methylation
Mexican Americans
Obesity ethnology
Obesity genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24058506
- Full Text :
- https://doi.org/10.1371/journal.pone.0073950