Imprinting and Maternal Effect Detection Using Partial Likelihood Based on Discordant Sibship Data

• Activity Number: 348
• Type: Contributed
• Date/Time: Tuesday, August 5, 2014 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Fangyuan Zhang*+ and Shili Lin
• Companies: and Ohio State University
• Keywords: ascertainment ; association study ; imprinting effect ; maternal effect ; partial likelihood

Abstract

Both genomic imprinting and maternal effects, as causes of parent-of-origin patterns in complex human diseases are increasingly explored. However, most methods either only model one of these two confounded epigenetic effects, or make strong yet unrealistic assumptions about population, such as allelic exchangeability and mating symmetry, to avoid over-parameterization. In this paper, we develop a partial Likelihood method for detecting Imprinting and Maternal Effects for a Discordant Sib-Pair design (LIME_DSP) that may also accommodate affected or unaffected siblings. By matching affected and unaffected probands and stratifying according to their familial genotypes, a partial likelihood component free of nuisance parameters can be extracted out from the full likelihood. Theoretical analysis shows that the partial maximum likelihood estimators based on the LIME_DSP approach are consistent and asymptotically normally distributed. A simulation study demonstrates the robust property of LIME_DSP and shows that it is a powerful approach without resolving to collect control families. To illustrate its practical utility, LIME_DSP was applied to the Framingham Heart Study data.