title: The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies.
abstract: Meta-analyses of genome-wide association studies (meta-GWASs) 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 cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders. First, we reviewed meta-GWASs 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 'depression' or 'depressive disorder' or 'depressive symptoms' or 'bipolar disorder' or 'lithium treatment response in bipolar disorder', or 'serotonin reuptake inhibitors treatment response in major depression'. 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 or dopamine receptors signaling, dopamine-DARPP32 feedback in cAMP signaling, circadian rhythm signaling and leptin signaling. Our review provides insights into the shared biological mechanisms of mood disorders and cardiometabolic diseases.
authors.affiliation: Discipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: A T
authors.initials: AT
authors.lastname: Amare
authors.affiliation: Discipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.|Northern Adelaide Local Health Network, Mental Health Services, Adelaide, SA, Australia.
authors.forename: K O
authors.initials: KO
authors.lastname: Schubert
authors.affiliation: Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Klingler-Hoffmann
authors.affiliation: School of Psychology, Faculty of Social and Behavioural Sciences, Flinders University, Adelaide, SA, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Cohen-Woods
authors.affiliation: Discipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: B T
authors.initials: BT
authors.lastname: Baune
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D003863:Depression / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D055106:Genome-Wide Association Study; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007328:Insulin; D050356:Lipid Metabolism / Q000235:genetics; D018020:Lithium Compounds / Q000627:therapeutic use; D009765:Obesity / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
chemical_list: D018692:Antimanic Agents; D005947:Glucose; D007328:Insulin; D018020:Lithium Compounds; D017367:Selective Serotonin Reuptake Inhibitors