Genetic association mapping at the crossroads: which test and why? Overview and practical guidelines

Area of Science:

• Genetics
• Statistical Genetics
• Bioinformatics

Background:

• Genetic association testing traditionally relied on case-control designs using genetic markers.
• Population stratification concerns led to the adoption of family-based association tests, notably the transmission/disequilibrium test (TDT).
• Recent advancements include extensions of the TDT and a resurgence of population-stratification-controlled case-control methods.

Purpose of the Study:

• To provide an overview of the evolution of genetic association testing methods.
• To enhance reader understanding of the fundamental principles behind various association testing approaches.
• To offer practical guidelines for selecting the most suitable genetic association test for specific research studies.

Main Methods:

• Review of historical and contemporary genetic association testing methodologies.
• Explanation of family-based tests, including extensions of the transmission/disequilibrium test (TDT).
• Discussion of case-control methods incorporating population stratification controls.

Main Results:

• The field has seen a shift from classic case-control studies to diverse family-based association tests.
• The transmission/disequilibrium test (TDT) and its variations are central to family-based association analysis.
• There is a renewed focus on refining case-control methods to address population stratification.

Conclusions:

• Genetic association testing methods have diversified significantly, offering various approaches to identify genetic links to diseases.
• Understanding the principles and practical applications of different tests, such as the TDT, is crucial for robust genetic research.
• This review aims to equip researchers with the knowledge to choose the optimal association testing strategy for their specific study design and objectives.