Amare A T, Schubert K O, Klingler-Hoffmann M, Cohen-Woods S, Baune B T
Discipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
Northern Adelaide Local Health Network, Mental Health Services, Adelaide, SA, Australia.
Transl Psychiatry. 2017 Jan 24;7(1):e1007. doi: 10.1038/tp.2016.261.
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.
全基因组关联研究的荟萃分析(meta-GWASs)以及候选基因研究已经确定了与心血管疾病、代谢疾病和情绪障碍相关的基因变异。尽管之前针对个体疾病状况(单一疾病)的研究取得了成功,但关于这些疾病之间共同的遗传风险的信息有限。本文对也与情绪障碍相关的心脏代谢疾病风险(CMD-R)基因进行了详细的综述和分析。首先,我们回顾了截至2016年1月发表的meta-GWASs,涉及“2型糖尿病、冠状动脉疾病、高血压”等疾病和/或“血压、肥胖、血脂水平、胰岛素和血糖相关性状”等风险因素。然后,我们在文献中搜索这些CMD-R基因与情绪障碍的已发表关联。我们纳入了那些报告至少一种CMD-R基因与“抑郁症”或“抑郁障碍”或“抑郁症状”或“双相情感障碍”或“双相情感障碍中的锂治疗反应”或“重度抑郁症中的5-羟色胺再摄取抑制剂治疗反应”存在显著关联的研究。我们的综述揭示了24个可能在情绪障碍和CMD-Rs之间共享的潜在多效性基因。这些基因包括MTHFR、CACNA1D、CACNB2、GNAS、ADRB1、NCAN、REST、FTO、POMC、BDNF、CREB、ITIH4、LEP、GSK3B、SLC18A1、TLR4、PPP1R1B、APOE、CRY2、HTR1A、ADRA2A、TCF7L2、MTNR1B和IGF1。对这些基因的通路分析揭示了重要的通路:促肾上腺皮质激素释放激素信号通路、AMPK信号通路、cAMP介导或G蛋白偶联受体信号通路、轴突导向信号通路、5-羟色胺或多巴胺受体信号通路、cAMP信号通路中的多巴胺-DARPP32反馈、昼夜节律信号通路和瘦素信号通路。我们的综述为情绪障碍和心脏代谢疾病的共同生物学机制提供了见解。