國家衛生研究院 NHRI:Item 3990099045/9500
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    题名: Generalization of rare variant association tests for longitudinal family studies
    作者: Chien, LC;Hsu, FC;Bowden, DW;Chiu, YF
    贡献者: Division of Biostatistics and Bioinformatics
    摘要: Given the functional relevance of many rare variants, their identification is frequently critical for dissecting disease etiology. Functional variants are likely to be aggregated in family studies enriched with affected members, and this aggregation increases the statistical power to detect rare variants associated with a trait of interest. Longitudinal family studies provide additional information for identifying genetic and environmental factors associated with disease over time. However, methods to analyze rare variants in longitudinal family data remain fairly limited. These methods should be capable of accounting for different sources of correlations and handling large amounts of sequencing data efficiently. To identify rare variants associated with a phenotype in longitudinal family studies, we extended pedigree-based burden (BT) and kernel (KS) association tests to genetic longitudinal studies. Generalized estimating equation (GEE) approaches were used to generalize the pedigree-based BT and KS to multiple correlated phenotypes under the generalized linear model framework, adjusting for fixed effects of confounding factors. These tests accounted for complex correlations between repeated measures of the same phenotype (serial correlations) and between individuals in the same family (familial correlations). We conducted comprehensive simulation studies to compare the proposed tests with mixed-effects models and marginal models, using GEEs under various configurations. When the proposed tests were applied to data from the Diabetes Heart Study, we found exome variants of POMGNT1 and JAK1 genes were associated with type 2 diabetes.
    日期: 2016-02
    關聯: Genetic Epidemiology. 2016 Feb;40(2):101-112.
    Link to: http://dx.doi.org/10.1002/gepi.21951
    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:000368725400002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84955498159
    显示于类别:[邱燕楓] 期刊論文

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