Gene-based analysis of bi-variate survival traits via functional regressions with applications to eye diseases

被引：0

作者：

Zhang, Bingsong ^{[1
]}

Chiu, Chi-Yang ^{[2
,3
]}

Yuan, Fang ^{[4
]}

Sang, Tian ^{[1
,5
]}

Cook, Richard J. ^{[6
]}

Wilson, Alexander F. ^{[3
]}

Bailey-Wilson, Joan E. ^{[3
]}

Chew, Emily Y. ^{[7
]}

Xiong, Momiao ^{[8
]}

Fan, Ruzong ^{[1
,3
]}

机构：

[1] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA

[2] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Div Biostat, Memphis, TN USA

[3] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD 21224 USA

[4] Kunming Med Univ, Sch Basic Med, Dept Biochem & Mol Biol, Kunming, Yunnan, Peoples R China

[5] Shanghai Univ Engn Sci, Sch Math Phys & Stat, Shanghai, Peoples R China

[6] Dept Stat & Actuarial Sci, Waterloo, ON, Canada

[7] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA

[8] Univ Texas Houston, Human Genet Ctr, Houston, TX 77025 USA

来源：

GENETIC EPIDEMIOLOGY | 2021年 / 45卷 / 05期

基金：

美国国家科学基金会;

关键词：

association study; common variants; complex diseases; functional data analysis; mixed effect Cox models; rare variants; ASSOCIATION ANALYSIS; QUANTITATIVE TRAITS; LINEAR-MODELS; LEVEL; RARE; METAANALYSIS; PROGRESSION; PLEIOTROPY; RISK;

D O I：

10.1002/gepi.22381

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genetic studies of two related survival outcomes of a pleiotropic gene are commonly encountered but statistical models to analyze them are rarely developed. To analyze sequencing data, we propose mixed effect Cox proportional hazard models by functional regressions to perform gene-based joint association analysis of two survival traits motivated by our ongoing real studies. These models extend fixed effect Cox models of univariate survival traits by incorporating variations and correlation of multivariate survival traits into the models. The associations between genetic variants and two survival traits are tested by likelihood ratio test statistics. Extensive simulation studies suggest that type I error rates are well controlled and power performances are stable. The proposed models are applied to analyze bivariate survival traits of left and right eyes in the age-related macular degeneration progression.

引用

页码：455 / 470

页数：16

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