Identification of gene networks jointly associated with depressive symptoms and cardiovascular health metrics using whole blood transcriptome in the Young Finns Study

Abstract

<p><strong>Background: </strong>Studies have shown that cardiovascular health (CVH) is related to depression. We aimed to identify gene networks jointly associated with depressive symptoms and cardiovascular health metrics using the whole blood transcriptome.</p><p><strong>Materials and methods: </strong>We analyzed human blood transcriptomic data to identify gene co-expression networks, termed gene modules, shared by Beck's depression inventory (BDI-II) scores and cardiovascular health (CVH) metrics as markers of depression and cardiovascular health, respectively. The BDI-II scores were derived from Beck's Depression Inventory, a 21-item self-report inventory that measures the characteristics and symptoms of depression. CVH metrics were defined according to the American Heart Association criteria using seven indices: smoking, diet, physical activity, body mass index (BMI), blood pressure, total cholesterol, and fasting glucose. Joint association of the modules, identified with weighted co-expression analysis, as well as the member genes of the modules with the markers of depression and CVH were tested with multivariate analysis of variance (MANOVA).</p><p><strong>Results: </strong>We identified a gene module with 256 genes that were significantly correlated with both the BDI-II score and CVH metrics. Based on the MANOVA test results adjusted for age and sex, the module was associated with both depression and CVH markers. The three most significant member genes in the module were <em>YOD1</em>, <em>RBX1</em>, and <em>LEPR</em>. Genes in the module were enriched with biological pathways involved in brain diseases such as Alzheimer's, Parkinson's, and Huntington's.</p><p><strong>Conclusions: </strong>The identified gene module and its members can provide new joint biomarkers for depression and CVH.</p>