Robust partial likelihood approach for detecting imprinting and maternal effects using case-control families

TL;DR

This paper introduces a robust partial likelihood method that combines different family study designs to effectively detect imprinting and maternal effects without relying on strong assumptions, improving accuracy in complex disease genetics.

Contribution

It proposes a novel partial likelihood approach that integrates case-control and family data, eliminating nuisance parameters and enhancing robustness in imprinting and maternal effect detection.

Findings

Correctly controls type I error rate

Exhibits little bias in estimates

Maintains reasonable power across scenarios

Abstract

Genomic imprinting and maternal effects are two epigenetic factors that have been increasingly explored for their roles in the etiology of complex diseases. This is part of a concerted effort to find the "missing heritability." Accordingly, statistical methods have been proposed to detect imprinting and maternal effects simultaneously based on either a case-parent triads design or a case-mother/control-mother pairs design. However, existing methods are full-likelihood based and have to make strong assumptions concerning mating type probabilities (nuisance parameters) to avoid overparametrization. In this paper we propose to augment the two popular study designs by combining them and including control-parent triads, so that our sample may contain a mixture of case-parent/control-parent triads and case-mother/control-mother pairs. By matching the case families with control families of the same structure and stratifying according to the familial genotypes, we are able to derive a partial likelihood that is free of the nuisance parameters. This renders unnecessary any unrealistic assumptions and leads to a robust procedure without sacrificing power. Our simulation study demonstrates that our partial likelihood method has correct type I error rate, little bias and reasonable power under a variety of settings.