Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies. 2811 39

A candidate gene and a genome-wide approach were combined to study the pharmacogenetics of antidepressant response and resistance. Investigated genes were selected on the basis of pleiotropic effect across psychiatric phenotypes in previous genome-wide association studies and involvement in antidepressant response. Three samples with major depressive disorder (total=671) were genotyped for 44 SNPs in 8 candidate genes (CACNA1C, CACNB2, ANK3, GRM7, TCF4, ITIH3, SYNE1, FKBP5). Phenotypes were response/remission after 4weeks of treatment and treatment-resistant depression (TRD). Genome-wide data from STAR*D were used to replicate findings for response/remission (n=1409) and TRD (n=620). Pathways including the most promising candidate genes were investigated in STAR*D for involvement in TRD. FKBP5 polymorphisms showed replicated but nominal associations with response, remission or TRD. CACNA1C rs1006737 and rs10848635 were the only polymorphisms that survived multiple-testing correction. In STAR*D the best pathway associated with TRD included CACNA1C (GO:0006942, permutated p=0.15). Machine learning models showed that independent SNPs in this pathway predicted TRD with a mean sensitivity of 0.83 and specificity of 0.56 after 10-fold cross validation repeated 100 times. FKBP5 polymorphisms appear good candidates for inclusion in antidepressant pharmacogenetic tests. Pathways including the CACNA1C gene may be involved in TRD and they may provide the base for developing multi-marker predictors of TRD.
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PMID:Pleiotropic genes in psychiatry: Calcium channels and the stress-related FKBP5 gene in antidepressant resistance. 2898