Abstract
Many statistical tests have been proposed for case-control data to detect disease association with multiple single nucleotide polymorphisms (SNPs) in linkage disequilibrium. The main reason for the existence of so many tests is that each test aims to detect one or two aspects of many possible distributional differences between cases and controls, largely due to the lack of a general and yet simple model for discrete genotype data. Here we propose a latent variable model to represent SNP data: the observed SNP data are assumed to be obtained by discretizing a latent multivariate Gaussian variate. Because the latent variate is multivariate Gaussian, its distribution is completely characterized by its mean vector and covariance matrix, in contrast to much more complex forms of a general distribution for discrete multivariate SNP data. We propose a composite likelihood approach for parameter estimation. A direct application of this latent variable model is to association testing with multiple SNPs in a candidate gene or region. In contrast to many existing tests that aim to detect only one or two aspects of many possible distributional differences of discrete SNP data, we can exclusively focus on testing the mean and covariance parameters of the latent Gaussian distributions for cases and controls. Our simulation results demonstrate potential power gains of the proposed approach over some existing methods.
Original language | English (US) |
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Pages (from-to) | 307-315 |
Number of pages | 9 |
Journal | Biometrics |
Volume | 68 |
Issue number | 1 |
DOIs | |
State | Published - Mar 2012 |
Externally published | Yes |
Keywords
- GWAS
- Genome-wide association study
- Latent model
- Logistic regression
- Multimarker analysis
- Multivariate discrete distribution
ASJC Scopus subject areas
- Statistics and Probability
- General Biochemistry, Genetics and Molecular Biology
- General Immunology and Microbiology
- General Agricultural and Biological Sciences
- Applied Mathematics