Single-Marker and Haplotype Analyses for DetectingImprinting Effects in Families with Both Parents and Families with One Parent

Abstract

Genomic imprinting is important in genetic trait study. Some statistical methods may be invalid or fail to detect linkage or association for imprinted genes. For case-parents trios, the parental-asymmetry test (PAT) is simple and powerful in detecting imprinting. Meanwhile, haplotype analysis is generally advantageous over single-marker analysis in complex trait study. As such, HAP-PAT, an extension of PAT, was constructed in haplotype analysis. However, it is common to collect families with both parents and those with only one parent. In this paper, when only one parent is available for each family, we develop 1-PAT to test for imprinting using single marker analysis. Combining families with both parent sand those with one parent, C-PAT is proposed. We also introduce HAP-1-PAT and HAP-C-PAT to test for imprinting using haplotype analysis. A permutation procedure is devised to determine the significance of HAP-1-PAT and HAP-C-PAT. The validity of the statistics is verified by simulation. A power study shows that using the additional information from families with one parent in the analysis greatly improves the power of the tests, compared to that based on families with both parents. Also, utilizing all affected children in each family, the proposed tests have a higher power than when only one affected child from each family is selected. Furthermore, there are significant gains in power from haplotype analysis compared to single-marker analysis.