國家衛生研究院 NHRI:Item 3990099045/10544
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    題名: Region-based association tests for sequencing data on survival traits
    作者: Chien, LC;Bowden, DW;Chiu, YF
    貢獻者: Division of Biostatistics and Bioinformatics
    摘要: Family-based designs enriched with affected subjects and disease associated variants can increase statistical power for identifying functional rare variants. However, few rare variant analysis approaches are available for time-to-event traits in family designs and none of them applicable to the X chromosome. We developed novel pedigree-based burden and kernel association tests for time-to-event outcomes with right censoring for pedigree data, referred to FamRATS (family-based rare variant association tests for survival traits). Cox proportional hazard models were employed to relate a time-to-event trait with rare variants with flexibility to encompass all ranges and collapsing of multiple variants. In addition, the robustness of violating proportional hazard assumptions was investigated for the proposed and four current existing tests, including the conventional population-based Cox proportional model and the burden, kernel, and sum of squares statistic (SSQ) tests for family data. The proposed tests can be applied to large-scale whole-genome sequencing data. They are appropriate for the practical use under a wide range of misspecified Cox models, as well as for population-based, pedigree-based, or hybrid designs. In our extensive simulation study and data example, we showed that the proposed kernel test is the most powerful and robust choice among the proposed burden test and the existing four rare variant survival association tests. When applied to the Diabetes Heart Study, the proposed tests found exome variants of the JAK1 gene on chromosome 1 showed the most significant association with age at onset of type 2 diabetes from the exome-wide analysis.
    日期: 2017-09
    關聯: Genetic Epidemiology. 2017 Sep;41(6):511-522.
    Link to: http://dx.doi.org/10.1002/gepi.22054
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0741-0395&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000407806800004
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85020191813
    顯示於類別:[邱燕楓] 期刊論文

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