Multilocus evaluation of genetic predictors of multiple sclerosis
| Autor: | I. A. Tuktarova, Klara Z. Bakhtiiarova, V. V. Erdman, Oksana V. Zaplakhova, Timur R. Galiullin, Yanina Timasheva, Timur R. Nasibullin |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Linkage disequilibrium Multiple Sclerosis Biology Logistic regression Polymorphism Single Nucleotide Receptors G-Protein-Coupled Polymorphism (computer science) Genetic model Genetics medicine Humans Genetic Predisposition to Disease Allele Genetic association Multiple sclerosis General Medicine Middle Aged Random effects model medicine.disease Bashkiria Case-Control Studies Female B7-2 Antigen Carrier Proteins T-Box Domain Proteins Demography |
| Zdroj: | Gene. 809 |
| ISSN: | 1879-0038 |
| Popis: | Background Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals. Objective Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation. Methods In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis. Associations were tested using logistic regression analysis under additive genetic model adjusted for sex. Meta-analysis of the study results in three populations was performed under fixed effects and random effects models. Results We demonstrate the association with multiple sclerosis of the five variants (INAVA rs7522462, EOMES rs11129295, C6orf10 rs3129934, CD86 rs9282641, and GPR65 rs2119704). The strongest association (OR = 2.16, CI:1.85–2.74, P = 2.53x10−13) was detected for rs3129934 polymorphism in the major histocompatibility region. Multilocus analysis has revealed 322 and 27 allelic patterns associated with multiple sclerosis in women and men, respectively. In women, the highest risk of MS was conferred by C6orf10 rs3129934*T/T + STAT3 rs744166*T combination (OR = 11.87), in men – by C6orf10 rs3129934*T + EOMES rs11129295*C + RPS6KB1 rs180515*C combination (OR = 3.25). Conclusion We confirm five associations with multiple sclerosis previously reported in genome-wide scans in Europeans in three ethnic groups from the Volga-Ural region of Russia. |
| Databáze: | OpenAIRE |
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