Genetic Associations of Anhedonia: Insights into Overlap of Mental and Somatic Disorders.

BACKGROUND: Anhedonia is characterized by a reduced ability to anticipate, experience, and/or learn about pleasure. This phenomenon has a transdiagnostic nature and is one of the key symptoms of mood disorders, schizophrenia, addictions, and somatic conditions. AIM: To evaluate the genetic architecture of anhedonia and its overlap with other mental disorders and somatic conditions. METHODS: We performed a genome-wide association study of anhedonia on a sample of 4,520 individuals from a Russian non-clinical population. Using the available summary statistics, we calculated polygenic risk scores (PRS) to investigate the genetic relationship between anhedonia and other psychiatric or somatic phenotypes. RESULTS: No variants with a genome-wide significant association were identified. PRS for major depression, bipolar disorder, and schizophrenia were significantly associated with anhedonia. Conversely, no significant associations were found between PRS for anxiety and anhedonia, which aligns well with existing clinical evidence. None of the PRS for somatic phenotypes attained a significance level after correction for multiple comparisons. A nominal significance for the anhedonia association was determined for omega-3 fatty acids, type 2 diabetes mellitus, and Crohn's disease. CONCLUSION: Anhedonia has a complex polygenic architecture, and its presence in somatic diseases or normal conditions may be due to a genetic predisposition to mood disorders or schizophrenia.

Lactase deficiency in Russia: multiethnic genetic study.

BACKGROUND: Lactase persistence-the ability to digest lactose through adulthood-is closely related to evolutionary adaptations and has affected many populations since the beginning of cattle breeding. Nevertheless, the contrast initial phenotype, lactase non-persistence or adult lactase deficiency, is still observed in large numbers of people worldwide. METHODS: We performed a multiethnic genetic study of lactase deficiency on 24,439 people, the largest in Russia to date. The percent of each population group was estimated according to the local ancestry inference results. Additionally, we calculated frequencies of rs4988235 GG genotype in Russian regions using the information of current location and birthplace data from the client's questionnaire. RESULTS: The attained results show that among all studied population groups, the frequency of GG genotype in rs4988235 is higher than the average in the European populations. In particular, the prevalence of lactase deficiency genotype in the East Slavs group was 42.8% (95% CI: 42.1-43.4%). We also investigated the regional prevalence of lactase deficiency based on the current place of residence. CONCLUSIONS: Our study emphasizes the significance of genetic testing for diagnostics, i.e., specifically for lactose intolerance parameter, as well as the scale of the problem of lactase deficiency in Russia which needs to be addressed by the healthcare and food sectors.

Association of common genetic variants with body mass index in Russian population.

BACKGROUND: Overweight is the scourge of modern society and a major risk factor for many diseases. For this reason, understanding the genetic component predisposing to high body mass index (BMI) seems to be an important task along with preventive measures aimed at improving eating behavior and increasing physical activity. METHODS: We analyzed genetic data of a European cohort (n = 21,080, 47.25% women, East Slavs ancestry >80%) for 5 frequently found genes in the context of association with obesity: IPX3 (rs3751723), MC4R (rs17782313), TMEM18 (rs6548238), PPARG (rs1801282) and FTO (rs9939609). RESULTS: Our study revealed significant associations of FTO (rs9939609) (ß = 0.37 (kg/m2)/allele, p = <2 × 10-16), MC4R (rs17782313) (ß = 0.28 (kg/m2)/allele, p = 5.79 × 10-9), TMEM18 (rs6548238) (ß = 0.29 (kg/m2)/allele, p = 2.43 × 10-8) with BMI and risk of obesity. CONCLUSIONS: The results confirm the contribution of FTO, M4CR, and TMEM18 genes to the mechanism of body weight regulation and control.

GWAS of depression in 4,520 individuals from the Russian population highlights the role of MAGI2 (S-SCAM) in the gut-brain axis.

We present the results of the depression Genome-wide association studies study performed on a cohort of Russian-descent individuals, which identified a novel association at chromosome 7q21 locus. Gene prioritization analysis based on already known depression risk genes indicated MAGI2 (S-SCAM) as the most probable gene from the locus and potential susceptibility gene for the disease. Brain and gut expression patterns were the main features highlighting functional relatedness of MAGI2 to the previously known depression risk genes. Local genetic covariance analysis, analysis of gene expression, provided initial suggestive evidence of hospital anxiety and depression scale and diagnostic and statistical manual of mental disorders scales having a different relationship with gut-brain axis disturbance. It should be noted, that while several independent methods successfully in silico validate the role of MAGI2, we were unable to replicate genetic association for the leading variant in the MAGI2 locus, therefore the role of rs521851 in depression should be interpreted with caution.