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      Novel epigenetic determinants of type 2 diabetes in Mexican-American families.

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          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.

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          Author and article information

          Journal
          Hum. Mol. Genet.
          Human molecular genetics
          1460-2083
          0964-6906
          Sep 15 2015
          : 24
          : 18
          Affiliations
          [1 ] South Texas Diabetes and Obesity Institute, University of Texas Health Sciences Center at San Antonio, Regional Academic Health Center, Harlingen, TX 78550, USA and kulkarnih@uthscsa.edu.
          [2 ] South Texas Diabetes and Obesity Institute, University of Texas Health Sciences Center at San Antonio, Regional Academic Health Center, Harlingen, TX 78550, USA and.
          [3 ] Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
          Article
          ddv232
          10.1093/hmg/ddv232
          4550817
          26101197
          1781c2b6-541a-4c45-8dc8-73536a2be92a
          © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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