example 2

Example 2 - Assigning liability class in LINKAGE:

motivation

In linkage analysis of a complex disease, one constantly faces the problem of phenotypic definition and disease model. For the first, it is not always clear whether a person is affected or not, because it depends on what phenotype or diagnostic is used. For the second, it is not clear whether one should use a dominant or a recessive model, or a reduced-penetrance model which is between the two extremes. In reality, it is likely that one wants to try all possibilities! And it involves a repeated changing of both the affection status and the disease model.
When using LINKAGE/FASTLINK program, the LINKAGE parameter file contains the disease model (penetrance table), and the LINKAGE pedigree file contains the affection status information.
LINKAGE provides a mechanism which adds another layer of complexity: the liability class. Liability class is a way in LINKAGE program to distinguish people by their age, gender, and other environmental factors, and each class has its own disease model (penetrance).
case 1: lung cancer

set up We assume you have two files: one contains the marker inforamtion and another contains the age and smoking information.
The first 5 columns in both files are consistent with the pre-MAKEPED LINKAGE pedigree.
The rest of the first file contains the marker information, whereas the rest of the second file contains three extra columns: affection status, age and the daily packs of cigarette consumed (-1 for unknown).
The script listed below will generate a liability class number according to the information in the second file. There will be 5 liability classes: unknown, young-light-smokers, old-light-smokers, young-heavy-smokers, old-heavy-smokers. One also needs to choose 5 sets of penetrance values to be included in the LINKAGE parameter file (not included in this script).
the Perl script (lia_lung.pl)
case 2: panic disorder

set up Besides a pre-MAKEPED LINKAGE pedigree file, one needs two more files. The first is a class definition file. And the second is a diagnostic code file, with 7-column information on panic disorder.
the Perl script (lia_panic.pl): running the script with the -d option will print a LINKAGE parameter file, and running it with the -p option will print a LINKAGE pedigree file with the extra column for liability class.

This is a companion page for W Li, F Haghighi, "Perl as a tool for linkage analysis", American Journal of Human Genetics, supplement to vol 65, page A260 (1999) (poster number 1452 at the Annual Meeting of American Society of Human Genetics 1999, San Francisco, CA)