Robust TDT-type Candidate-Gene Association Tests

• Activity Number: 318
• Type: Contributed
• Date/Time: Wednesday, August 14, 2002 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section*
• Author(s): Gang Zheng*+ and Boris Freidlin and Joseph Gastwirth
• Affiliation(s): National Institute of Health/NHLBI and National Cancer Institute and George Washington University
• Keywords: Association tests ; Efficiency ; Robust tests ; Transmission disequilibrium

Abstract

The transmission disequilibrium test (TDT) uses non-transmitted parental alleles as controls to study the association between a marker and a disease. The power of the TDT test depends on the underlying genetic model. When the marker is a candidate gene, the TDT is the optimal test, assuming the additive model holds. Related methods have been obtained for other modes of inheritance. When the true model is unknown, the use of a procedure designed for one model usually leads to a substantial loss of power if another genetic model is the true one. The general approach of efficiency robustness leads to two robust procedures for TDT-type association tests. When the plausible range of alternative models is wide (e.g. dominant through recessive) the maximum (MAX) of several test statistics, each of which is optimal for quite different models, has good power under all genetic models. In situations where the set of possible models can be narrowed (e.g., dominant through additive), a simple linear combination (MERT) also performs well. In general, the MAX has great power-robustness than the TDT for the study of candidate genes.