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Novel epigenetic determinants of type 2 diabetes in Mexican-American families.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2015 Sep 15; Vol. 24 (18), pp. 5330-44. Date of Electronic Publication: 2015 Jun 22. - Publication Year :
- 2015
-
Abstract
- Although DNA methylation is now recognized as an important mediator of complex diseases, the extent to which the genetic basis of such diseases is accounted for by DNA methylation is unknown. In the setting of large, extended families representing a minority, high-risk population of the USA, we aimed to characterize the role of epigenome-wide DNA methylation in type 2 diabetes (T2D). Using Illumina HumanMethylation450 BeadChip arrays, we tested for association of DNA methylation at 446 356 sites with age, sex and phenotypic traits related to T2D in 850 pedigreed Mexican-American individuals. Robust statistical analyses showed that (i) 15% of the methylome is significantly heritable, with a median heritability of 0.14; (ii) DNA methylation at 14% of CpG sites is associated with nearby sequence variants; (iii) 22% and 3% of the autosomal CpG sites are associated with age and sex, respectively; (iv) 53 CpG sites were significantly associated with liability to T2D, fasting blood glucose and insulin resistance; (v) DNA methylation levels at five CpG sites, mapping to three well-characterized genes (TXNIP, ABCG1 and SAMD12) independently explained 7.8% of the heritability of T2D (vi) methylation at these five sites was unlikely to be influenced by neighboring DNA sequence variation. Our study has identified novel epigenetic indicators of T2D risk in Mexican Americans who have increased risk for this disease. These results provide new insights into potential treatment targets of T2D.<br /> (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Child
Chromosome Mapping
CpG Islands
DNA Methylation
Diabetes Mellitus, Type 2 epidemiology
Epigenomics
Female
Gene Expression Profiling
Genetic Association Studies
Genome-Wide Association Study
Humans
Inheritance Patterns
Insulin Resistance genetics
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Quantitative Trait, Heritable
Risk Factors
Sex Factors
Texas epidemiology
Texas ethnology
Young Adult
Diabetes Mellitus, Type 2 genetics
Epigenesis, Genetic
Mexican Americans genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 24
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 26101197
- Full Text :
- https://doi.org/10.1093/hmg/ddv232