A Comprehensive Lifestyle Index And Its Associations With DNA Methylation And Type 2 Diabetes Among Ghanaian Adults: The Rodam Study.

Abstract

Background A series of modifable lifestyle factors, such as diet quality, physical activity, alcohol intake, and smoking, may drive the rising burden of type 2 diabetes (T2DM) among sub-Saharan Africans globally. It is unclear whether epi‑ genetic changes play a mediatory role in the associations between these lifestyle factors and T2DM. We assessed the associations between a comprehensive lifestyle index, DNA methylation and T2DM among Ghanaian adults. Methods We used whole-blood Illumina 450 k DNA methylation data from 713 Ghanaians from the Research on Obesity and Diabetes among African Migrants (RODAM) study. We constructed a comprehensive lifestyle index based on established cut-ofs for diet quality, physical activity, alcohol intake, and smoking status. In the T2DM-free discovery cohort (n=457), linear models were ftted to identify diferentially methylated positions (DMPs) and difer‑ entially methylated regions (DMRs) associated with the lifestyle index after adjustment for age, sex, body mass index (BMI), and technical covariates. Associations between the identifed DMPs and the primary outcome (T2DM), as well as secondary outcomes (fasting blood glucose (FBG) and HbA1c), were determined via logistic and linear regression models, respectively. Results In the present study population (mean age: 52±10 years; male: 42.6%), the comprehensive lifestyle index showed a signifcant association with one DMP annotated to an intergenic region on chromosome 7 (false discovery rate (FDR)=0.024). Others were annotated to ADCY7, SMARCE1, AHRR, LOXL2, and PTBP1 genes. One DMR was iden‑ tifed and annotated to the GFPT2 gene (familywise error rate (FWER) from bumphunter bootstrap=0.036). None of the DMPs showed signifcant associations with T2DM; directions of efect were positive for the DMP in the AHRR and inverse for all the other DMPs. Higher methylation of the ADCY7 DMP was associated with higher FBG (p=0.024); LOXL2 DMP was associated with lower FBG (p=0.023) and HbA1c (p=0.049); and PTBP1 DMP was associated with lower HbA1c (p=0.002). Conclusions In this explorative epigenome-wide association study among Ghanaians, we identifed one DMP and DMR associated with a comprehensive lifestyle index not previously associated with individual lifestyle factors.