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    题名: A non-threshold region-specific method for detecting rare variants in complex diseases
    作者: Hsieh Ai-Ru, Dao-Peng Chen, Amrita Sengupta Chattopadhyay, Ying-Ju Li, Chien-Ching Chang and Cathy SJ Fann
    日期: 2017-11-30
    上传时间: 2019-09-24 12:10:58 (UTC+8)
    出版者: Hsieh
    摘要: A region-specific method, NTR (non-threshold rare) variant detection method, was developed—it does not use the threshold for defining rare variants and accounts for directions of effects. NTR also considers linkage disequilibrium within the region and accommodates common and rare variants simultaneously. NTR weighs variants according to minor allele frequency and odds ratio to combine the effects of common and rare variants on disease occurrence into a single score and provides a test statistic to assess the significance of the score. In the simulations, under different effect sizes, the power of NTR increased as the effect size increased, and the type I error of our method was controlled well. Moreover, NTR was compared with several other existing methods, including the combined multivariate and collapsing method (CMC), weighted sum statistic method (WSS), sequence kernel association test (SKAT), and its modification, SKAT-O. NTR yields comparable or better power in simulations, especially when the effects of linkage disequilibrium between variants were at least moderate. In an analysis of diabetic nephropathy data, NTR detected more confirmed disease-related genes than the other aforementioned methods. NTR can thus be used as a complementary tool to help in dissecting the etiology of complex diseases.
    關聯: PLoS One. 12(11), p.0188566
    DOI: 10.1371/journal.pone.0188566
    显示于类别:[統計學系暨研究所] 期刊論文

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