Covariate adjusted inference of parent-of-origin effects using case–control mother–child paired multilocus genotype data

It is of great interest to identify parent-of-origin effects (POEs) since POEs play an important role in many human heritable disorders and human early life growth and development. POE is sometimes referred to as imprinting effect in the literature. Compared with the standard logistic regression analyses, retrospective likelihood-based statistical methods are more powerful in identifying POEs when data are collected from related individuals retrospectively. However, none of existing retrospective-based methods can appropriately incorporate covariates that should be adjusted for if they are confounding factors. In this paper, a novel semiparametric statistical method, M-HAP, is developed to detect POEs by fully exploring available information from multilocus genotypes of case–control mother–child pairs and covariates. Some large sample properties are established for M-HAP. Finite sample properties of M-HAP are illustrated by extensive simulation studies and real data applications to the Jerusalem Perinatal Study and the Danish National Birth Cohort study, which confirm the desired superiority of M-HAP over some existing methods. M-HAP has been implemented in the updated R package CCMO.