The genetic overlap between mood disorders and cardio-metabolic diseases: A systematic review of genome wide and candidate gene studies

Meta-analyses of genome-wide association studies (meta-GWAS) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases, and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardio-metabolic diseases risk (CMD-R) genes that are also associated with mood disorders. Firstly, we reviewed meta-GWA studies published until January 2016, for the diseases “type 2 diabetes, coronary artery disease, hypertension” and/or for the risk factors “blood pressure, obesity, plasma lipid levels, insulin and glucose related traits”. We then searched the literature for published associations of these CMD-R genes with mood disorders. We considered studies that reported a significant association of at least one of the CMD-R genes and “depressive disorder” OR “depressive symptoms” OR “bipolar disorder” OR “lithium treatment”, OR “serotonin reuptake inhibitors treatment”. Our review revealed 24 potential pleiotropic genes that are likely to be shared between mood disorders and CMD-Rs. These genes include MTHFR, CACNA1D, CACNB2, GNAS, ADRB1, NCAN, REST, FTO, POMC, BDNF, CREB, ITIH4, LEP, GSK3B, SLC18A1, TLR4, PPP1R1B, APOE, CRY2, HTR1A, ADRA2A, TCF7L2, MTNR1B, and IGF1. A pathway analysis of these genes revealed significant pathways: corticotrophin-releasing hormone signaling, AMPK signaling, cAMP-mediated or G-protein coupled receptor signaling, axonal guidance signaling, serotonin and dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling, circadian rhythm signaling and leptin signaling. Our findings provide insights in to the shared biological mechanisms of mood disorders and cardio-metabolic diseases.