Comparison of Association Testing Processes

Examine the features and capabilities of the association testing processes (found in the GWAS Testing and Other Association Testing Genetics subcategories) in the table below.

Process

Tests for association between trait(s) and...

In Unrelated samples, Families, or Both1?

Taking into account

Using these methods

Can accommodate traits of type...

Tests marker effects and GxE interaction effects?

Binary

Continuous

Other (nominal, ordinal, or survival)

Case-Control Association

Markers

Unrelated

Population structure (when applying VIF for genomic control)

Pearson chi-square tests, Fisher exact tests, C-A trend test

Y

 

 

 

PCA for Population Stratification

SNPs (coded numerically)

Unrelated

Population structure

EIGENSTRAT (Price et al. 2006)

Y

Y

 

 

SNP-Trait Association2 3

SNPs

Both

Fixed and random effect

Regression, ANOVA, and linear mixed models

Y

Y

Y

Y

Process Description4

SNPs (represented by genotype probabilities)

Both

The uncertainty of called genotypes; fixed and random effects

Regression, ANOVA, and linear mixed models

Y

Y

Y

Y

Survey SNP-Trait Association

SNPs

Unrelated

Complex survey designs and very large data sets

Regression models and frequency table statistics for survey data

Y

Y

 

Y

Quantitative TDT

Markers

Families5

Population structure through use of families and covariates

Various quantitative transmission disequilibrium tests

Y

Y

 

 

TDT6

Markers

Families7

Population structure through use of families

Transmission/disequilibrium test and variations of it

Y

 

 

 

GWAS Meta-Analysis

SNPs, from multiple studies

 

Multiple GWASs

Meta-analysis methods: Stouffer et al. 1949; Wang and Bushman 1999

 

 

 

 

Multiple SNP-Trait Association

Numerically coded genotypes from multiple SNPs at a time

Both

Fixed and random effects

Regression models, kernel machine method, Hotelling's T-squared test, and Sequence Kernel Association Test (SKAT)8

Y

 

Y

Y

Rare Variant Tutorial

Rare variants

 

The value of guidance in choosing processes and parameters

Genetics Rare Variants Workflow, Rare Variant Association

See help on underlying processes.

Rare Variant Association

SNPs (rare variants and optionally common variants)

Unrelated

Multiple variants within a gene or pathway

VT, WSS, aSum-P, KBAC, CMAT, C-alpha, and others

Y

Y

 

 

Pleiotropic Association

SNPs

Unrelated

Testing for multiple traits at once

Regression, ANOVA, and MANOVA

 

Y

 

Y

Marker-Trait Association9

Markers

Both

Fixed and random effects

Regression, ANOVA, and linear mixed models

Y

Y

 

Y

SNP-SNP Interactions

Interactions between pairs of SNPs

Both

SNP main effects, other fixed and random effects

Regression, ANOVA, and linear mixed models

Y

Y

Y

 

SNP Interaction Discovery

Interactions between pairs of SNPs

Unrelated

 

Penalized Logistic Regression (PLR) (Park and Hastie 2008)

Y

 

 

 

Q-K Mixed Model2 10

SNPs

Both

Population structure and family relatedness (represented by Q and K matrices, respectively)

Regression, ANOVA, and linear mixed models (Yu et al. 2006)

Y

Y

 

Y

Return to GWAS Testing or Other Association Testing.

See Genetics for other subcategories.