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.

Glucose metabolism dysregulation at the onset of mental illness is not limited to first episode psychosis: A systematic review and meta‐analysis

“…Research suggests that altered systemic inflammation, shared genetic make‐up between SMIs and DM2, and adverse gestational events may play a role in this pre‐diabetic condition. There is some support for these arguments (Amare, Schubert, Klingler‐Hoffmann, Cohen‐Woods, & Baune, ; Garcia‐Rizo, Fernandez‐Egea, Bernardo, & Kirkpatrick, ; Goldsmith, Rapaport, & Miller, ; Greenhalgh et al, ; Thakore, ; van Nimwegen et al, ). Systemic inflammation is a feature of both disorders.…”

Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

“…Interestingly, decreased AADC activity has been reported in obese mice fed a high‐fat high‐simple‐carbohydrate diet (Moreira‐Rodrigues et al., 2012). Moreover, genome wide and candidate gene studies identified SLC18A1 as one potential pleiotropic gene overlapped between mood disorders and cardiometabolic diseases (Amare, Schubert, Klingler‐Hoffmann, Cohen‐Woods, & Baune, 2017). Also, a genetic variation in SLC18A1 made statistically significant contributions to BMI in Chinese subjects (Chen et al., 2013).…”

Pharmacogenomics in the treatment of mood disorders: Strategies and Opportunities for personalized psychiatry

“…A recent review of GWAS and candidate gene studies provided evidence for a cross-disorder genetic overlap between mood disorders and cardiometabolic abnormalities. This evidence indicated a genetic basis for the impact that medical comorbidities have on treatment outcomes in mood disorders [3]. Polygenic analysis can be applied in such cases to estimate the extent of genetic overlap as well as to identify polygenic predictors [3].…”

“…Moreover, patients with MDD and BPD often show overlapping clinical features [25]. It is estimated that about 47% of the genetic risk factors are shared between MDD and BPD [21] and a shared genetic risk was revealed between mood disorders and other psychiatric and medical morbidities [3,21,22]. Environmental risk factors such as childhood abuse (physical, sexual, or psychological) are also frequently reported to be associated with both disorders [1].…”