scholarly journals Robust Joint Analysis with Data Fusion in Two-Stage Quantitative Trait Genome-Wide Association Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Dong-Dong Pan ◽  
Wen-Jun Xiong ◽  
Ji-Yuan Zhou ◽  
Ying Pan ◽  
Guo-Li Zhou ◽  
...  
Keyword(s):  
Quantitative Traits ◽  
Genetic Model ◽  
Association Studies ◽  
Statistical Significance ◽  
Genome Wide Association ◽  
Joint Analysis ◽  
Genome Wide Association Studies ◽  
Two Stage ◽  
Rheumatic Arthritis ◽  
Genome Wide

Genome-wide association studies (GWASs) in identifying the disease-associated genetic variants have been proved to be a great pioneering work. Two-stage design and analysis are often adopted in GWASs. Considering the genetic model uncertainty, many robust procedures have been proposed and applied in GWASs. However, the existing approaches mostly focused on binary traits, and few work has been done on continuous (quantitative) traits, since the statistical significance of these robust tests is difficult to calculate. In this paper, we develop a powerfulF-statistic-based robust joint analysis method for quantitative traits using the combined raw data from both stages in the framework of two-staged GWASs. Explicit expressions are obtained to calculate the statistical significance and power. We show using simulations that the proposed method is substantially more robust than theF-test based on the additive model when the underlying genetic model is unknown. An example for rheumatic arthritis (RA) is used for illustration.

scholarly journals Host Genome-Wide Association Study of Infant Susceptibility to Shigella-Associated Diarrhea

2021 ◽  
Vol 89 (6) ◽  
Author(s):  
Dylan Duchen ◽  
Rashidul Haque ◽  
Laura Chen ◽  
Genevieve Wojcik ◽  
Poonum Korpe ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Diarrheal Disease ◽  
Genetic Model ◽  
Association Studies ◽  
Host Cells ◽  
Genome Wide Association ◽  
Joint Analysis ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Host Genetic

ABSTRACT Shigella is a leading cause of moderate-to-severe diarrhea globally and the causative agent of shigellosis and bacillary dysentery. Associated with 80 to 165 million cases of diarrhea and >13% of diarrheal deaths, in many regions, Shigella exposure is ubiquitous while infection is heterogenous. To characterize host-genetic susceptibility to Shigella-associated diarrhea, we performed two independent genome-wide association studies (GWAS) including Bangladeshi infants from the PROVIDE and CBC birth cohorts in Dhaka, Bangladesh. Cases were infants with Shigella-associated diarrhea (n = 143) and controls were infants with no Shigella-associated diarrhea in the first 13 months of life (n = 446). Shigella-associated diarrhea was identified via quantitative PCR (qPCR) threshold cycle (CT) distributions for the ipaH gene, carried by all four Shigella species and enteroinvasive Escherichia coli. Host GWAS were performed under an additive genetic model. A joint analysis identified protective loci on chromosomes 11 (rs582240, within the KRT18P59 pseudogene; P = 6.40 × 10−8; odds ratio [OR], 0.43) and 8 (rs12550437, within the lincRNA RP11-115J16.1; P = 1.49 × 10−7; OR, 0.48). Conditional analyses identified two previously suggestive loci, a protective locus on chromosome 7 (rs10266841, within the 3′ untranslated region [UTR] of CYTH3; Pconditional = 1.48 × 10−7; OR, 0.44) and a risk-associated locus on chromosome 10 (rs2801847, an intronic variant within MPP7; Pconditional = 8.37 × 10−8; OR, 5.51). These loci have all been indirectly linked to bacterial type 3 secretion system (T3SS) activity, its components, and bacterial effectors delivered into host cells. Host genetic factors that may affect bacterial T3SS activity and are associated with the host response to Shigella-associated diarrhea may provide insight into vaccine and drug development efforts for Shigella-associated diarrheal disease.

Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies

2006 ◽  
Vol 38 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Andrew D Skol ◽  
Laura J Scott ◽  
Gonçalo R Abecasis ◽  
Michael Boehnke
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Joint Analysis ◽  
Genome Wide Association Studies ◽  
Two Stage ◽  
Genome Wide

scholarly journals Robust Association Tests for the Replication of Genome-Wide Association Studies

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Jungnam Joo ◽  
Ju-Hyun Park ◽  
Bora Lee ◽  
Boram Park ◽  
Sohee Kim ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Genetic Model ◽  
Association Studies ◽  
Statistical Significance ◽  
Genetic Models ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Association Tests ◽  
Genome Wide ◽  
Wide Range

In genome-wide association study (GWAS), robust genetic association tests such as maximum of three CATTs (MAX3), each corresponding to recessive, additive, and dominant genetic models, the minimumpvalue of Pearson’s Chi-square test with 2 degrees of freedom, and CATT based on additive genetic model (MIN2), genetic model selection (GMS), and genetic model exclusion (GME) methods have been shown to provide better power performance under wide range of underlying genetic models. In this paper, we demonstrate how these robust tests can be applied to the replication study of GWAS and how the overall statistical significance can be evaluated using the combined test formed bypvalues of the discovery and replication studies.

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