Genetic risk factors for depression in patients with coronary artery disease

^1,2Qing Ling Duan, ³Marie-Pierre Dubé, ⁴François Lesperance, ³Pierre Théroux, ⁵Nancy Frasure-Smith, ³Amina Barhdadi, ¹Guy A Rouleau, ⁶Jeanne M McCaffery
¹Department of Medicine, Université de Montréal and Centre Hospitalier de l’Université de Montréal, Montreal,Quebec, Canada, ²Department of Human Genetics, McGill University, Montreal,Quebec, Canada, ³Department of Medicine, Université de Montréal and the Research Centre, Montreal Heart Institute, Montreal,Quebec, Canada, ⁴Department of Psychiatry, Centre Hospitalier de l'Université de Montréal, Montreal,Quebec, Canada, ⁵Department of Psychiatry and School of Nursing, McGill University, the Research Center, Montreal Heart Institute, the Department of Psychiatry Université de Montréal, and the Research Center, Centre Hospitalier de l’Université de Montréal, Montreal,Quebec, Canada, ⁶Weight Control and Diabetes Research Center, Brown Medical School and The Miriam Hospital, Providence, United States of America

It is well established that depressive symptoms (DEP) and coronary artery disease (CAD) often co-occur. However, little attention has been paid to the potential for common genetic mechanisms to underlie, in part, the association between DEP and CAD. In this study, we examined nearly 700 single nucleotide polymorphisms (SNPs) across 59 genes, which code for key elements of biological pathways thought to contribute to this association, in two independent cohorts of French-Canadian cardiac patients, the ESCAPE (N = 596) and POLYMORPHISME cohorts (N = 484). Evidence of CAD was ascertained from hospital records, which indicated that the patients had >50% blockage in at least one major coronary artery or a documented myocardial infarction, and DEP was defined using transformed Beck Depression Inventory-II scores. This study is the first to identify replicated genetic associations with DEP in CAD. Specifically, we report that a SNP within one candidate gene was strongly associated with DEP in the two independent cohorts of French-Canadian cardiac patients (p < 0.005). In exploratory analyses combining the cohorts, the same SNP remained significantly associated with DEP (p = 0.00006). Other genes were also strongly associated with depressive symptoms (p <= 0.001) but were not significant using the Bonferroni correction for multiple comparisons. These results point to novel mechanisms that may underlie depression in CAD and suggest that genetic variation may account, in part, for the observed association between depression and CAD.