An improved robust association test for GWAS with multiple diseases

被引：13

作者：

Chen, Zhongxue ^{[1
]}

Huang, Hanwen ^{[2
]}

Ng, Hon Keung Tony ^{[3
]}

机构：

[1] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA

[2] Univ Georgia, Dept Epidemiol & Biostat, Athens, GA 30602 USA

[3] So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA

来源：

STATISTICS & PROBABILITY LETTERS | 2014年 / 91卷

关键词：

Chi-square partition; Genetic model; Robust test; Trend test; GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; DIFFERENTIALLY METHYLATED LOCI; 3,000 SHARED CONTROLS; WEIGHTED Z-TEST; GENETIC ASSOCIATION; COMBINING PROBABILITIES; COMMON DISEASES; TREND TESTS; P-VALUES;

D O I：

10.1016/j.spl.2014.04.015

中图分类号：

O21 [概率论与数理统计]; C8 [统计学];

学科分类号：

020208 ; 070103 ; 0714 ;

摘要：

In a previous study, we proposed a new design and analysis strategy for Genome-wide Association Studies (GWAS) with multiple diseases but no controls. We have proposed to use an overall chi-square test to test for the association between an SNP with any one of the diseases. The overall chi-square test is not sensitive to the underlying model assumption; however, it does not use the information about the trend among the relative risks of the three genotypes. In this study, we propose a new overall test based on the chi-square partition method. The overall p-value of the proposed approach can be estimated by combining independent p-values from the more powerful one-sided tests which incorporate the trend among the relative risks. Simulation study and real data application show that the proposed test is more powerful and robust. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：153 / 161

页数：9

共 39 条

[1]

Agresti A, 2013, Categorical data analysis, V3rd

[2]

[Anonymous], 1932, STAT METHODS RES WOR

[3] TESTS FOR LINEAR TRENDS IN PROPORTIONS AND FREQUENCIES [J].

ARMITAGE, P .

BIOMETRICS, 1955, 11 (03) :375-386

[4] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[5] Is the weighted z-test the best method for combining probabilities from independent tests? [J].

Chen, Z. .

JOURNAL OF EVOLUTIONARY BIOLOGY, 2011, 24 (04) :926-930

[6]

Chen Z., 2013, STAT METHODS MED RES

[7] Design and analysis of multiple diseases genome-wide association studies without controls [J].

Chen, Zhohgxue ;

Huang, Hanwen ;

Ng, Hon Keung Tony .

GENE, 2012, 510 (01) :87-92

[8] On the optimally weighted z-test for combining probabilities from independent studies [J].

Chen, Zhongxue ;

Nadarajah, Saralees .

COMPUTATIONAL STATISTICS & DATA ANALYSIS, 2014, 70 :387-394

[9] Association tests through combining p-values for case control genome-wide association studies [J].

Chen, Zhongxue .

STATISTICS & PROBABILITY LETTERS, 2013, 83 (08) :1854-1862

[10] Detecting differentially methylated loci for Illumina Array methylation data based on human ovarian cancer data [J].

Chen, Zhongxue ;

Huang, Hanwen ;

Liu, Jianzhong ;

Ng, Hon Keung Tony ;

Nadarajah, Saralees ;

Huang, Xudong ;

Deng, Youping .

BMC MEDICAL GENOMICS, 2013, 6

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