Exploring the role of environmental factors in association and linkage studies

We analyzed some simulated data to assess the success of statistical method ologies to establish the role of the environmental factors (EF) and to iden tify associated and linked markers. We considered five replicates for each of the four studies, and, with the knowledge of the generating model, conce ntrated our analyses on chromosomes (CH) 1, 3, and 5. To determine the infl uence of EF and associated markers on the affection status (AS), we utilize d chi-square tests for independence and recursive partitioning (via the CAR T software). To identify linked markers, we scanned the relevant chromosome s with nonparametric multipoint linkage (NPL) and transmission/disequilibri um tests. These analyses were performed on the whole data set as well as on subsets of individuals and families defined by exposure to EF. CART correc tly selected the associated marker (D1G024) and EF1 for Study (ST) 1 and di d not generate trees for the other studies. NPL identified the relevant reg ions on CH3 and CH5 but failed to do so for CH1, except in ST4. Stratifying families by exposure to EF1 did not consistently increase sensitivity of N PL to the relevant CH3 markers, but did help characterize the genetic heter ogeneity and identify linked families. (C) 1999 Wiley-Liss, Inc.