1. A LOG-LINEAR APPROACH TO DEAL WITH MULTIPLE AFFECTED SIBLING IN DETECTING MATERNAL EFFECT AND PARENT-OF- ORIGIN EFFECT Jingyuan Yang Research Meeting 05/08/2008

2. Risk Factors (1) A person carries disease allele(s); (2) His or her mother carries disease allele(s) and passes some antigen or mRNA to the person during pregnancy which could increase the susceptibility of the person; (3) Interaction of (1) and (2): effect of a specific maternal-fetal genotype combination. Notes: Once (1) is detected as a risk factor, then origin of each allele comes into play as a secondary objective of investigation (parent-of-origin effect). Both (2) and (3) are considered as maternally “mediated” effect

3. Schaid et al (1993): Genotype Relative Risks In this paper, only (1) was considered as the risk factor, i.e.: Relative risk is defined as the ratio between the disease susceptibility of two randomly selected persons who have different genetic backgrounds. They were: Data in this model are the counts of 6 different mating types

4. Weinberg et al (1998) and Sinsheimer et al (2003) Weinberg’s LL-LRT: Sinsheimer’s MFG test:

5. Maximize the Likelihood Direct approach Generalized linear approach

6. Multiple Sibling

7. Simulation Simulation was conducted by decomposing the likelihood in another way Compute, and simulate the parental genotypes according to the number of affected sibling in that family. Then Use P(C|M, F, D) to generate the genotype of each child in a nuclear family.