Design and Analysis for Studying Major Cancer Genes
Sining Chen
Department of Environmental Health Sciences
Johns Hopkins School of Public Health
Friday, November 16, 2007, 12:30–1:30 pm
GEMS classroom, 3rd Floor in
Shriner's Building
Coffee, tea, and cookies will be provided
Abstract
Using BRCA1 and BRCA2 in familial breast cancer as an example, we discuss a
number of designs and analyses for characterizing rare
genetic variants in hereditary syndromes. Specifically, we present two
approaches to analyze heavily ascertained family data.
The retrospective likelihood approach
uses the likelihood of genetic test results conditioning on the
family history.
It takes full advantage of the Mendelian transmission
of mutated alleles and provides unbiased estimates.
The ascertainment-conditional likelihood approach conditions on the event
of ascertainment and models the probability of ascertainment through a
family history summary variable.
It has higher efficiency than the retrospective likelihood
and remains unbiased under appropriate modeling of the ascertainment event.
Finally we present a meta-analysis of BRCA penetrance studies.