论文标题

测试与距离相关的复杂疾病中的遗传相互作用

Testing for genetic interactions in complex disease with distance correlation

论文作者

Castro-Prado, Fernando, Costas, Javier, Edelmann, Dominic, González-Manteiga, Wenceslao, Penas, David R.

论文摘要

理解上毒(遗传相互作用)可能会阐明常见疾病的基因组基础,包括由于其高度社会经济负担,例如精神分裂症,因此具有最大关注的疾病。距离相关是一种关联度量,它表征了随机变量之间的一般统计独立性,而不仅仅是线性变量。在这里,我们提出距离相关性是从单核苷酸多态性(SNP)的病例对照数据中检测上毒的新工具。在方法论方面,我们强调了测试统计数据的显式渐近分布的推导。我们表明,在文献中发现的重新采样技术不切实际的情况下,这是获得足够的计算速度以在实践中使用的方法的唯一方法。我们的模拟显示出令人满意的意义校准,以及比现有方法的校准以及可比或更好的功率。我们将技术应用于精神分裂症遗传学数据集,并获得生物学上合理的见解。

Understanding epistasis (genetic interaction) may shed some light on the genomic basis of common diseases, including disorders of maximum interest due to their high socioeconomic burden, like schizophrenia. Distance correlation is an association measure that characterises general statistical independence between random variables, not only the linear one. Here, we propose distance correlation as a novel tool for the detection of epistasis from case-control data of single-nucleotide polymorphisms (SNPs). On the methodological side, we highlight the derivation of the explicit asymptotic distribution of the test statistic. We show that this is the only way to obtain enough computational speed for the method to be used in practice, in a scenario where the resampling techniques found in the literature are impractical. Our simulations show satisfactory calibration of significance, as well as comparable or better power than existing methodology. We conclude with the application of our technique to a schizophrenia genetics dataset, obtaining biologically sound insights.

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