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

Pinakhina, Daria; Yermakovich, Danat; Vergasova, Ekaterina; Kasyanov, E. D.; Рукавишников, Г. В.; Rezapova, Valeriia; Kolosov, Nikita; Sergushichev, Alexey; Popov, Iaroslav; Kovalenko, Elena V.; Ilinskaya, Anna; Kim, Anna; Plotnikov, Nikolay; Ilinsky, Valery; Незнанов, Н. Г.; Мазо, Г. Н.; Кибитов, А.О.; Rakitko, Alexander; Artomov, Mykyta

doi:10.3389/fgene.2022.972196

Cited by 5 publications

(2 citation statements)

References 79 publications

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“…First, PGS was calculated on the basis of a limited number of examined genetic variants, thus resulting in a small value of the proportion of variance explained by PGS. It should also be mentioned that to date, GWAS of depression conducted in a cohort of Russian descent was carried out [49]; however, summary statistics from this study remain publicly unavailable. Therefore, for the sensitivity analysis, we calculated PGS based on effect estimates from GWAS of depression/neuroticism of Western Europeans.…”

Section: Discussionmentioning

confidence: 99%

A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level

Казанцева¹,

Davydova²,

Enikeeva³

et al. 2023

Genes

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The risk of depression could be evaluated through its multifactorial nature using the polygenic score (PGS) approach. Assuming a “clinical continuum” hypothesis of mental diseases, a preliminary assessment of individuals with elevated risk for developing depression in a non-clinical group is of high relevance. In turn, epidemiological studies suggest including social/lifestyle factors together with PGS to address the “missing heritability” problem. We designed regression models, which included PGS using 27 SNPs and social/lifestyle factors to explain individual differences in depression levels in high-education students from the Volga–Ural region (VUR) of Eurasia. Since issues related to population stratification in PGS scores may lead to imprecise variant effect estimates, we aimed to examine a sensitivity of PGS calculated on summary statistics of depression and neuroticism GWAS from Western Europeans to assess individual proneness to depression levels in the examined sample of Eastern Europeans. A depression score was assessed using the revised version of the Beck Depression Inventory (BDI) in 1065 young adults (age 18–25 years, 79% women, Eastern European ancestry). The models based on weighted PGS demonstrated higher sensitivity to evaluate depression level in the full dataset, explaining up to 2.4% of the variance (p = 3.42 × 10−7); the addition of social parameters enhanced the strength of the model (adjusted r2 = 15%, p < 2.2 × 10−16). A higher effect was observed in models based on weighted PGS in the women group, explaining up to 3.9% (p = 6.03 × 10−9) of variance in depression level assuming a combined SNPs effect and 17% (p < 2.2 × 10−16)—with the addition of social factors in the model. We failed to estimate BDI-measured depression based on summary statistics from Western Europeans GWAS of clinical depression. Although regression models based on PGS from neuroticism (depression-related trait) GWAS in Europeans were associated with a depression level in our sample (adjusted r2 = 0.43%, p = 0.019—for unweighted model), the effect was mainly attributed to the inclusion of social/lifestyle factors as predictors in these models (adjusted r2 = 15%, p < 2.2 × 10−16—for unweighted model). In conclusion, constructed PGS models contribute to a proportion of interindividual variability in BDI-measured depression in high-education students, especially women, from the VUR of Eurasia. External factors, including the specificity of rearing in childhood, used as predictors, improve the predictive ability of these models. Implementation of ethnicity-specific effect estimates in such modeling is important for individual risk assessment.

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Section: Discussionmentioning

confidence: 99%

A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level

Казанцева¹,

Davydova²,

Enikeeva³

et al. 2023

Genes

View full text Add to dashboard Cite

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“…Проведенный биоинформатический анализ показал, что экспрессия гена MAGI-2 наиболее высока в отдельных структурах мозга, а также в кишечнике. Менделевский рандомизационный анализ подтвердил причинно-следственные связи воспалительных заболеваний кишечника и количественного фенотипа депрессии на основе HADS-D [47].…”

Section: Introductionunclassified

Genetic Comorbidity of Depression and Somatic Diseases: Rationale Study Design in a Population Cohort Using Polygenic Risk Scores

Kibitov,

Mazo,

Kasyanov

et al. 2024

Psychiatry

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Background: depression is widespread in the population, and one of the leading causes of disability, reduced life expectancy and mortality. Such a significant effect is based on the high frequency of comorbidity of depression with severe chronic somatic diseases. Genetic studies can provide tools to identify groups with a high level of genetic risk of comorbidity of these diseases in a population for their early specific prevention. The aim of review article was to justify the methodology and design of research directed for joint genetic risk markers for depression and chronic somatic diseases linked with each other in terms of genetic comorbidity. Publication, patients and methods: population cohort of depressive patients examined using international clinical and psychometric instruments. The study will allow: 1) to evaluate the risks of developing chronic somatic diseases in a population of patients with depression; 2) to assess the predictive power of polygenic risk scores of somatic diseases for symptoms of depression and somatic diseases in a population sample; 3) to validate polygenic risk scores for genetic comorbidity of depression and somatic diseases in a qualitatively described sample of patients using modern clinical and psychometric tools. Conclusion: the methodology and results of the study can be used for an evidence-based preventive approach in the field of mental and physical health.

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A Replication Study of GWAS-Associated Variants in the TUFM, SH2B1, ZNF638, NEGR1, ATP2A1, EXOC4, and CSE1L Genes and Cognitive Abilities

Kazantseva,

Davydova,

Enikeeva

et al. 2023

Russ J Genet

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

Cited by 5 publications

References 79 publications

A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level

A Combined Effect of Polygenic Scores and Environmental Factors on Individual Differences in Depression Level

Genetic Comorbidity of Depression and Somatic Diseases: Rationale Study Design in a Population Cohort Using Polygenic Risk Scores

A Replication Study of GWAS-Associated Variants in the TUFM, SH2B1, ZNF638, NEGR1, ATP2A1, EXOC4, and CSE1L Genes and Cognitive Abilities

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