Robust trend tests for genetic association in case-control studies using family data.

Area of Science:

• Genetics
• Statistical genetics
• Disease association studies

Background:

• Genetic association studies aim to link genetic variations to diseases.
• Traditional trend tests for genetic association can lose power if the underlying genetic model is misspecified.
• Family-based studies can account for correlations among relatives but are sensitive to model assumptions.

Purpose of the Study:

• To develop robust trend tests for genetic association analysis in case-control family studies.
• To enhance statistical power for detecting genetic associations when the mode of inheritance is unknown.
• To provide reliable methods for complex disease genetic studies.

Main Methods:

• Developed two novel robust trend tests for case-control family data.
• Adjusted trend tests to account for correlations within families and complex pedigrees.
• Evaluated test performance across a range of potential genetic models.

Main Results:

• The robust trend tests demonstrated relatively good power across various genetic models.
• The developed methods are less sensitive to misspecification of the genetic model.
• Applied trend tests and robust trend tests to the Collaborative Study on the Genetics of Alcoholism dataset.

Conclusions:

• Robust trend tests offer a powerful and reliable approach for genetic association studies with family data.
• These methods are particularly valuable for complex diseases with unknown modes of inheritance.
• The study provides practical tools for analyzing genetic association in family-based cohorts.