Gene-environment interactions and the affected-sib-pair designs

In genetic mapping of complex traits, the affected-sib-pair method (ASP) an d the transmission disequilibrium test (TDT) are two methods of choice. The major appeal of both ASP and TDT is that they do not require the knowledge of mode of inheritance underlying the trait in question. The relative ease and economy for data collection also is the reason for their popularity. T he basic idea of the ASP is to identify genes or chromosomal regions throug h identifying genetic similarity based on phenotypical similarity. TDT, on the other hand, detects susceptibility genes through detecting unusual tran smission patterns in families. Since phenotypic similarity can also be caus ed by environmental similarity, we investigate how the presence of gene-env ironment interaction (GEI) affects the power of both methods. For a simple one locus-one-risk-factor model, our results indicate that, in the presence of GEI, methods developed based on marginal penetrance functions (i.e, ign oring the risk factor) can give spurious results. The triangular restrictio n on allele-sharing probability may no longer be valid. If the environment effect is strong, using exposure-discordant affected sib pairs may have adv antage over other designs. Above all, a genetic model involving both geneti c and environmental factors behaves differently from a single-locus genetic model. Copyright (C) 2000 S. Karger AG, Basel.