title: Semiparametric inference on the penetrances of rare genetic mutations based on a case-family design.
abstract: A formal semiparametric statistical inference framework is proposed for the evaluation of the age-dependent penetrance of a rare genetic mutation, using family data generated under a case-family design, where phenotype and genotype information are collected from first-degree relatives of case probands carrying the targeted mutation. The proposed approach allows for unobserved risk factors that are correlated among family members. Some rigorous large sample properties are established, which show that the proposed estimators were asymptotically semi-parametric efficient. A simulation study is conducted to evaluate the performance of the new approach, which shows the robustness of the proposed semiparamteric approach and its advantage over the corresponding parametric approach. As an illustration, the proposed approach is applied to estimating the age-dependent cancer risk among carriers of the MSH2 or MLH1 mutation.
authors: Institute of Biostatistics, School of Life Science, Fudan University, P.R.C ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, U.S.A.
authors: Hong
authors: H
authors: Zhang
authors: Donglin
authors: D
authors: Zeng
authors: Sylviane
authors: S
authors: Olschwang
authors: Kai
authors: K
authors: Yu