JSM 2005 Online Program

Abstract #303873

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Activity Number:	237
Type:	Contributed
Date/Time:	Tuesday, August 9, 2005 : 8:30 AM to 10:20 AM
Sponsor:	Section on Statistics in Epidemiology
Abstract - #303873
Title:	An Approach to Adjustment of the Penetrance Obtained from Case Proband Studies
Author(s):	Ilya Novikov*+
Companies:	Gertner Institute for Epidemiology and Health Policy Research
Address:	Tel Hashomer, Ramat Gan, 52621, Israel
Keywords:	BRCA1/BRCA2 mutation ; penetrance ; case proband ; family studies ; size bias
Abstract:	Estimation of penetrance is one of the main problems in genetic epidemiology. The penetrance of a certain disease may be estimated using various types of studies. One of the most popular, family studies, often used a proband defined as a carrier of a genotype of interest having the disease (case proband). Such a design is known to be size-biased. In these type of studies, "size" is the number of diseased carriers in a family. Approximate estimates of the bias have been proposed. However, the estimates are usable only when the probability of a diseased carrier to be selected as a proband is small. We propose another estimate valid for any selection probability. We discuss two ways of correction for the size bias: weighted crude estimation of penetrance and a multiple regression with "size" and "carrier" as covariates. When not all family members have been genotyped, one can use the number of diseased persons in a family as the "size." The results of intensive simulations for both logistic and Cox regressions are presented. They show multiple regression leads to a far better elimination of the bias than the weighted estimates.

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