Genetic analysis of a complex disease in the presence of an environmental risk factor.
The role of a gene in a disease may be hidden by the presence of another risk factor such as an environmental factor. In that case, stratifying the data according to this factor strengthens power to detect linkage or association. We followed this strategy on the simulated data provided by GAW11. The transmission/disequilibrium test (TDT) and the maximum likelihood score (MLS) were performed on the first replicate of 100 sib pairs from the population in which the disease risk was significantly influenced by an environmental factor (E1). However, only the TDT was powerful enough to detect one of the four loci involved in the genetic determination of the disease. The MLS showed no evidence for linkage after taking into account the fact that multiple tests were performed. Even when stratifying the sample according to the presence of E1, no additional loci could be detected. Given the simulated models, 100 sib pairs are too low a sample size for a systematic screening of the genome, which in this case was an analysis of 300 markers.
Eichenbaum-Voline
S
S
Institute for Medical Statistics, University of Bonn, Germany.
Baur
M P
MP
Knapp
M
M
D004777:Environment; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008126:Lod Score; D008957:Models, Genetic; D015233:Models, Statistical; D012307:Risk Factors