Discordant Sibship Design for Detecting Imprinting and Maternal Effects Based on Partial Likelihood

• Activity Number: 168
• Type: Topic Contributed
• Date/Time: Monday, August 10, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Fangyuan Zhang* and Shili Lin
• Companies: The Ohio State University and The Ohio State University
• Keywords: Ascertainment ; Association study ; Imprinting effect ; Maternal effect ; Partial Likelihood ; Discordant sib-pair design

Abstract

We develop a partial Likelihood method for detecting Imprinting and Maternal Effects for a Discordant Sib-Pair design (LIME_DSP ) utilizing all available sibship data without the need to recruit separate control families. By matching affected and unaffected probands and stratifying according to their familial genotypes, a partial likelihood component free of nuisance parameters can be extracted from the full likelihood. This alleviates the need to make assumptions about nuisance parameters. Theoretical analysis shows that the partial maximum likelihood estimators based on the LIME_DSP approach are consistent and asymptotically normally distributed. Based on the close-form formula for computing information, we compared a study design with more independent families versus one with larger families by keeping the total number of individuals needed to be genotyped fixed. We further carried out a simulation study, which demonstrates the robust property of LIME_DSP and shows that it is a powerful approach without resolving to collecting control families. To illustrate its practical utility, LIME_DSP was applied to a club foot dataset and to the Framingham Heart Study.