In:
Human Heredity, S. Karger AG, Vol. 69, No. 4 ( 2010), p. 229-241
Abstract:
〈 i 〉 Background/Aims: 〈 /i 〉 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. 〈 i 〉 Methods: 〈 /i 〉 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. 〈 i 〉 Results: 〈 /i 〉 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. 〈 i 〉 Conclusion: 〈 /i 〉 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.
Type of Medium:
Online Resource
ISSN:
0001-5652
,
1423-0062
Language:
English
Publisher:
S. Karger AG
Publication Date:
2010
detail.hit.zdb_id:
1482710-4
SSG:
12
