Investigating causality in the association between DNA methylation and type 2 diabetes using bidirectional two-sample Mendelian randomisation.
Diana L Juvinao-QuinteroGemma C SharpEleanor C M SandersonCaroline L ReltonHannah R ElliottPublished in: Diabetologia (2023)
We identified one CpG mapping to a gene related to the metabolism of lipids (DHCR24) as a novel causal biomarker for risk of type 2 diabetes. CpGs within the same gene region have previously been associated with type 2 diabetes-related traits in observational studies (BMI, waist circumference, HDL-cholesterol, insulin) and in Mendelian randomisation analyses (LDL-cholesterol). Thus, we hypothesise that our candidate CpG in DHCR24 may be a causal mediator of the association between known modifiable risk factors and type 2 diabetes. Formal causal mediation analysis should be implemented to further validate this assumption.
Keyphrases
- type diabetes
- dna methylation
- genome wide
- body mass index
- glycemic control
- risk factors
- copy number
- low density lipoprotein
- gene expression
- cardiovascular disease
- genome wide identification
- body weight
- high resolution
- physical activity
- mass spectrometry
- adverse drug
- fatty acid
- weight loss
- depressive symptoms
- genome wide analysis
- adipose tissue