Abstract
Background/Aims: To improve the efficiency of disease locus localization in association mapping using case-parent designs and to assess or account for the main covariate effects and gene-covariate interaction effects, while localizing the disease locus. Methods: The present study extends a multipoint fine-mapping approach to incorporate covariates into the association mapping of case-parent designs through parametric and non-parametric modeling. This approach is based on the expected preferential-allele-transmission statistics for transmission from either parent to an affected child. Results: Simulation studies indicate that the efficiency in estimating the disease locus increases considerably when incorporating a covariate associated with the disease. This is especially true when the genetic effect of the disease locus is small. The proposed approach was applied to a young-onset hypertension data sample. The relative efficiency of estimating the locus of young-onset hypertension increases 110-fold after incorporating triglyceride into the association mapping while localizing the disease variant in the lipoprotein lipase gene in the non-parametric model. By incorporating the information of SNP variants into the fine-mapping, the proposed method further assesses the gene-gene interactions between the SNP and the disease locus. Conclusion: With the incorporation of covariates, the proposed method cannot only improve efficiency in estimating disease loci, but can also elucidate the etiology of a complex disease.
Original language | English (US) |
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Pages (from-to) | 229-241 |
Number of pages | 13 |
Journal | Human Heredity |
Volume | 69 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2010 |
Externally published | Yes |
Keywords
- Case-parent designs
- Gene-covariate interactions
- Gene-environment interactions
- Gene-gene interactions
- Non-parametric
- Parametric
- Relative efficiency
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)