Conditional Likelihood Score Tests for Familial Association Studies with Parental Genotypes

• Activity Number: 189
• Type: Invited
• Date/Time: Tuesday, August 13, 2002 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology*
• Author(s): Zhaohai Li*+ and Mitchell Gail and Joseph Gastwirth
• Affiliation(s): George Washington University and National Cancer Institute and George Washington University

Abstract

Both population-based and family-based case control studies are used to test whether particular alleles (genotypes) are associated with a complex disease. Family-based methods were introduced to control for cryptic population stratification (CPS). This paper presents the full likelihood function for family-based association studies for nuclear families ascertained on the basis of their number of affected and unaffected children. The portion of the likelihood unaffected by CPS, called conditional likelihood, is used to obtain score tests with proper size in the presence of CPS. Under either the additive or multiplicative model, the TDT is shown to be the optimal score test when the family has only one affected child. Thus, the class of score tests explored can be considered as a general family of TDT-like procedures. The relative informativeness of the various mating types is assessed using the Fisher information. When the additive model is true, families with parental mating types AaxAa are most informative. Under the dominant (recessive) model, however, a family with mating type Aaxaa (AAxAa) is more informative than a family with doubly.