Major depression and atherosclerotic disease: Linking shared genetics to pathways in blood, brain, heart, and atherosclerotic plaques

). Eight genomic regions harbored potentially shared causal variants, including one on chromosome 7 linking MD with any stroke, ischemic stroke and CAD. Altered expression of 16 genes in blood, 10 in brain, and 6 in heart was found causal for MD etiology. In atherosclerotic plaques, one gene was linked to MD at nominal significance only. Major depression and atherosclerotic diseases share genetic risk potentially acting in depression pathophysiology through expression of genes in blood, brain and heart tissues. Involvement of atherosclerotic plaques in depression etiology was not supported. Identified pathways could guide the development of new treatments to prevent depression-heightened atherosclerotic risk.