Institute of Biochemistry and Genetics of Ufa Federal Research Centre of Russian Academy of Sciences, 71 October Avenue, 450054 Ufa, Russia; Section of Genomics of Common Disease, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, Du Cane Road, London W12 0NN, United Kingdom; Bashkir State Medical University, 3 Lenin Street, 450008 Ufa, Russia.
Institute of Biochemistry and Genetics of Ufa Federal Research Centre of Russian Academy of Sciences, 71 October Avenue, 450054 Ufa, Russia.
Gene. 2022 Jan 30;809:146008. doi: 10.1016/j.gene.2021.146008. Epub 2021 Oct 14.
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.
Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation.
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.
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) 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 rs3129934T/T + STAT3 rs744166T combination (OR = 11.87), in men - by C6orf10 rs3129934T + EOMES rs11129295C + RPS6KB1 rs180515*C combination (OR = 3.25).
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.
全基因组关联研究在欧洲血统的人群中确定了许多多发性硬化症的易感基因位点，但由于混杂和不同的连锁不平衡模式掩盖了真正的关联信号，这些关联在其他人群中并不总是可重复的。
我们的目的是在俄罗斯伏尔加-乌拉尔地区的三个种族同源人群中鉴定多发性硬化症的遗传预测因子。
在迄今为止最大的俄罗斯多发性硬化症研究中，涉及来自俄罗斯联邦巴什科尔托斯坦共和国的 2048 名参与者（641 名多发性硬化症患者和 1407 名未受影响的个体），我们对先前确定的多发性硬化症全基因组信号进行了复制分析。使用逻辑回归分析在调整性别后的加性遗传模型下测试关联。在固定效应和随机效应模型下对三个群体的研究结果进行荟萃分析。
我们证明了五个变体（INAVA rs7522462、EOMES rs11129295、C6orf10 rs3129934、CD86 rs9282641 和 GPR65 rs2119704）与多发性硬化症相关。在主要组织相容性区域中，rs3129934 多态性的关联最强（OR=2.16，CI：1.85-2.74，P=2.53x10）。多基因分析分别在女性和男性中发现了 322 和 27 个与多发性硬化症相关的等位基因模式。在女性中，MS 的最高风险由 C6orf10 rs3129934T/T+STAT3 rs744166T 组合赋予（OR=11.87），在男性中由 C6orf10 rs3129934T+EOMES rs11129295C+RPS6KB1 rs180515*C 组合赋予（OR=3.25）。
我们在俄罗斯伏尔加-乌拉尔地区的三个种族群体中证实了五个与全基因组扫描在欧洲人身上报告的多发性硬化症相关的关联。
