Incorporating covariates into multipoint association mapping in the case-parent design

Yen Feng Chiu, Kung Yee Liang, Wen Harn Pan

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)229-241
Number of pages13
JournalHuman Heredity
Volume69
Issue number4
DOIs
StatePublished - Apr 2010

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)

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