DNA Methylation in Risk for Cognitive Impairment and Type 2 Diabetes in a Mexican American Cohort

Abstract

Background Alzheimer’s disease (AD) and type 2 diabetes (T2D) are among the leading causes of mortality among the growing aging Mexican American population (≥ 65 years old) in the US (Vega et al. 2017). In comparison to their non‐Hispanic white counterparts who most likely develop inflammation associated AD, aging Mexican Americans have an earlier onset of AD and metabolism related predisposition for AD (O'Bryant et al. 2010). Mild cognitive impairment (MCI) is a phenotype that often leads to AD and is also prevalent in this cohort (O'Bryant et al. 2013). The risks for AD, MCI and T2D are multifactorial, involving a form of epigenetic regulation called methylation where a methyl group is added to the cytosine base in DNA (Shao et al. 2017; Juvinao‐Quintero et al. 2019). We aim to elucidate an epigenetic association between cognitive impairment (identified here as AD and MCI), and T2D that is unique to the Mexican American population. Method A total of 551 aging participants from the Texas Alzheimer’s Research and Care Consortium (TARCC) consisting of 252 non‐Hispanic white individuals and 299 Mexican Americans were selected, after quality control. First, participants were stratified into groups of individuals diagnosed with cognitive impairment (CI) alone and controls without CI within each ethnic group. Secondly, this cohort was stratified into individuals with T2D alone and controls without T2D. Thirdly, participants were stratified into those with both CI and T2D versus normal healthy controls. Lastly, any differential methylation associated with each ethnic group will be compared and contrasted. Peripheral blood drawn from participants was used to obtain individual methylation profiles using the Illumina Infinium MethylationEPIC chip array. Differential methylation was assessed using the Chip Analysis Methylation Pipeline (ChAMP), limma and cate packages in R. The Beta MIxture Quantile dilation (BMIQ) method was used for data normalization. Result Results will be analyzed using gene set enrichment and pathway analysis tools. Conclusion Identifying possible methylation sites associated with CI and T2D could contribute towards developing ethnicity‐specific biomarkers for Mexican Americans.