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Statistical Colocalization of Genetic Risk Variants for Related Autoimmune Diseases in the Context of Common Controls

机译:共同控制背景下相关自身免疫性疾病遗传风险变异的统计共定位

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摘要

Identifying whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent datasets. Here we extend two colocalization methods to allow for the shared control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases, type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis, revealed 90 regions that were associated with at least one disease, 33 (37%) of which with two or more disorders. Nevertheless, for 14 of these 33 shared regions there was evidence that causal variants differed. We identified novel disease associations in 11 regions previously associated with one or more of the other three disorders. Four of eight T1D-specific regions contained known type 2 diabetes candidate genes: COBL, GLIS3, RNLS and BCAR1, suggesting a shared cellular etiology.
机译:鉴定是否共享了相关疾病的潜在因果变体可以确定多因素疾病的重叠病因。共定位方法可以解开共享的和不同的因果变量。但是,现有方法需要独立的数据集。在这里,我们扩展了两种共定位方法,以允许在比较跨疾病的全基因组关联研究结果时常用的共享控制设计。我们对四种自身免疫性疾病,1型糖尿病(T1D),类风湿性关节炎,乳糜泻和多发性硬化症的分析揭示了与至少一种疾病相关的90个区域,其中33个(37%)与两种或多种疾病有关。但是,对于这33个共享区域中的14个,有因果差异的证据。我们在先前与其他三种疾病中的一种或多种相关的11个区域中发现了新型疾病关联。八个T1D特异性区域中的四个包含已知的2型糖尿病候选基因:COBL,GLIS3,RNLS和BCAR1,表明存在共同的细胞病因。

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