Anhedonia in mood disorders and somatic diseases: results of exploratory Mendelian randomization analysis

• Published in: Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova Vol. 123; no. 4. Vyp. 2; p. 65
• Main Authors: Kasyanov, E D, Pinakhina, D V, Rakitko, A S, Vergasova, E O, Yermakovich, D P, Rukavishnikov, G V, Malyshko, L V, Popov, Ya V, Kovalenko, E V, Ilinskaya, A Yu, Kim, A A, Plotnikov, N A, Neznanov, N G, Ilinsky, V V, Kibitov, A O, Mazo, G E
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 2023
• Subjects: Anhedonia; Cross-Sectional Studies; Female; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis - methods; Phenotype; Polymorphism, Single Nucleotide; breast cancer; GWAS; Mendelian randomization; somatic diseases; mood disorders; anhedonia
• ISSN: 1997-7298
• DOI: 10.17116/jnevro202312304265

To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study. This cross-sectional study included 4520 participants, of which 50.4% ( =2280) were female. The mean age was 36.8 (S.D.=9.8) years. Participants were pheno-nailed based on the DSM-5 criteria for anhedonia in the framework of depression. An episode of anhedonia exceeding 2 weeks during life was reported by 57.6% ( =2604) of participants. A genome-wide association study (GWAS) of the anhedonia phenotype was performed, as well as a Mendelian randomization analysis using summary statistics of large-scale GWASs on psychiatric and somatic phenotypes. The GWAS on anhedonia did not reveal the variants with genome-wide significant association ( <10 ). The most significant ( =9.71×10 ) was the variant rs296009 (chr5:168513184) in an intron of the slit guidance ligand 3 (SLIT3) gene. Using Mendelian randomization, nominally significant ( <0.05) causal associations of anhedonia with 24 phenotypes were identified, which can be divided into 5 main groups: psychiatric/neurological diseases, inflammatory diseases of the digestive system, respiratory diseases, oncological diseases and metabolic disorders. The most significant causal effects of anhedonia were found for breast cancer ( =0.0004, OR=0.9986, 95% confidence interval (CI) (0.9978-0.999)), minimal depression phenotype ( =0.009, OR=1.004, 95% CI (1.001-1.007)), as well as for apolipoprotein A ( =0.01, OR=0.973, 95% CI (0.952-0.993)) and respiratory diseases ( =0.01, OR=0.9988, 95% CI (0.9980-0.9997)). The polygenic nature of anhedonia may cause the risks of comorbidity of this phenotype with a wide range of somatic diseases, as well as may be associated with mood disorders.