Validation of linkage by sampling based on environmental exposures.
After detecting linkage in one sample, most researchers will attempt to validate this finding in another sample. Three strategies for validating a primary linkage were compared, with a focus on methods that might be appropriate in the presence of gene x environment interaction. First, a validation sample was collected and analyzed using the same ascertainment procedure and methods as the primary sample. Second, a sample of families with particular exposure patterns were ascertained subsequent to a significant test for heterogeneity due to the exposure in the primary sample. A third strategy ascertained by exposure status when exposure-defined subgroup tests were significant in the primary sample. The second strategy reduced the number of false positive linkage signals identified through exposure subgroup identification (i.e., the third strategy), but in this GAW11 data that contained no qualitative gene x environment interactions, it had poor sensitivity. Power to detect heterogeneity depends on the differences in risk between exposed and unexposed.
Greenwood
C M
CM
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Brewer
C G
CG
Morgan
K
K
D004777:Environment; D008040:Genetic Linkage; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008957:Models, Genetic; D012984:Software