It is now well established that depressive symptoms predict coronary artery disease (CAD), both in community samples with no known CAD and among patients who have already experienced a clinical event. Nonetheless, the mechanisms underlying this association remain unclear. Of the proposed common mechanisms, the potential for common genetic variants to contribute to both depression and cardiovascular disease has received little attention to date. Depression and CAD morbidity and mortality are each heritable in twin and family studies. In addition, the one twin study to address covariation of depression and CAD suggested that 43 percent of the common variance between depressive symptoms and CAD was attributable to common genetic effects. In this proposal, we aim to target genes coding for components of three plausible biological pathways, inflammation, serotonin-mediated platelet aggregation and omega-3 metabolism, as a first step in identifying candidate genes that may account for the association between depressive symptoms and CAD. Specifically, we will haplotype: 1) ICAM-1, IL6, and CRP within the inflammation pathway; 2) the genes that code for the serotonin2 receptor (5HT2) and the serotonin transporter (5HTT), mediating serotonin-induced platelet aggregation; and 3) the genes that code for delta-6 desaturase (FADS2) and delta-5 desaturase (FADS1), essential to omega-3 fatty acid metabolism. Participants will be 1074 individuals with established CAD and 462 age- and sex- matched controls. Depressive symptoms will be characterized from responses to the Beck Depression Inventory (BDI). Importantly, all participants are of French-Canadian descent (self-report of four grandparents of French-Canadian descent). French-Canadians are a homogeneous, founder population, indicating a simpler haplotype structure and reduced risk of population substructure or admixture, thereby, substantially improving the likelihood of detection of genetic association.
| McCaffery, Jeanne M; Duan, Qing Ling; Frasure-Smith, Nancy et al. (2009) Genetic predictors of depressive symptoms in cardiac patients. Am J Med Genet B Neuropsychiatr Genet 150B:381-8 |
| Duan, Qing Ling; Dube, Marie-Pierre; Frasure-Smith, Nancy et al. (2007) Additive effects of obesity and TCF7L2 variants on risk for type 2 diabetes among cardiac patients. Diabetes Care 30:1621-3 |
| McCaffery, Jeanne M; Frasure-Smith, Nancy; Dube, Marie-Pierre et al. (2006) Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin. Psychosom Med 68:187-200 |
