Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study

Abstract

AbstractBackgroundThe relations of alcohol consumption and gene expression remain to be elucidated in large study samples.ObjectivesTo study the relationship between alcohol consumption, gene expression, and cardiovascular disease (CVD) risk factors.MethodsWe performed cross-sectional association analysis of whole blood derived gene expression levels with alcohol consumption in 5,531 Framingham Heart Study (FHS) participants (mean age 55 years; 54% women) by splitting the sample into a discovery sample and a replication sample (2:1 ratio) using independent pedigrees. We also examined the cross-sectional association of alcohol-associated genes with three CVD risk factors: obesity, hypertension, and diabetes. Linear mixed models or generalized estimation equations were used to quantify associations accounting for familial relationship and multiple covariates.ResultsWe identified 25 alcohol-associated genes (false discovery rate < 0.05 in the discovery sample and Bonferroni corrected P < 0.05 in the replication sample). We further showed cross-sectional associations of 16 alcohol-associated genes with obesity, nine genes with hypertension, and eight genes with diabetes (all P < 0.002). For example, we observed decrease in expression of PROK2 (β = -0.0018; 95%CI: -0.0021, -0.0007; P = 6.5e-5) and PAX5 (β = -0.0014; 95%CI: -0.0021, -0.0007; P = 6.5e-5) per 1 g/day increase in alcohol consumption. Consistent with our previous observation on the inverse association of alcohol consumption with obesity and positive association of alcohol consumption with hypertension, we found that PROK2 was positively associated with obesity (OR = 1.42; 95%CI: 1.17, 1.72; P = 4.5e-4) and PAX5 was negatively associated with hypertension (OR = 0.73; 95%CI: 0.59, 0.89; P = 1.6e-3). We also observed that alcohol consumption was positively associated with expression of ABCA13 (β = 0.0012; 95%CI: 0.0007, 0.0017; P = 1.3e-6) and ABCA13 was positively associated with diabetes (OR = 2.57; 95%CI: 1.73, 3.84; P = 3.5e-06); this finding, however, was inconsistent with our observation on the inverse association between alcohol consumption and diabetes.ConclusionsWe observed that alcohol consumption was associated with whole blood expression levels of 25 genes in middle aged to older adults in the FHS. In addition, complex relationships may exist between alcohol-associated genes and CVD risk factors.