Role of DNA Methylation in Type 2 Diabetes Etiology: Using Genotype as a Causal Anchor

This study uses genotypic information as a causal anchor to help decipher the likely role of DNA methylation measured in peripheral blood in the etiology of type 2 diabetes. Illumina HumanMethylation450 BeadChip data were generated on 1,018 young individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. In stage 1, 118 unique associations between published type 2 diabetes single nucleotide polymorphisms (SNPs) and genome-wide methylation (methylation quantitative trait loci [mQTLs]) were identified. In stage 2, a further 226 mQTLs were identified between 202 additional independent non–type 2 diabetes SNPs and CpGs identified in stage 1. Where possible, associations were replicated in independent cohorts of similar age. We discovered that around half of known type 2 diabetes SNPs are associated with variation in DNA methylation and postulated that methylation could either be on a causal pathway to future disease or could be a noncausal biomarker. For one locus (KCNQ1), we were able to provide further evidence that methylation is likely to be on the causal pathway to disease in later life.

Source: Diabetes - May 22, 2017 Category: Endocrinology Authors: Elliott, H. R.; Shihab, H. A.; Lockett, G. A.; Holloway, J. W.; McRae, A. F.; Smith, G. D.; Ring, S. M.; Gaunt, T. R.; Relton, C. L. Tags: Genetics/Genomes/Proteomics/Metabolomics Source Type: research