Nicholas Schork - The future of genetic case-control studies

The power and simplicity of the case/control study design makes it an appealing strategy for testing the relationship between particular genetic polymorphisms (or haplotypes) and traits or diseases. Despite this fact, there are a number of problems that plague the use and interpretation of genetic case/control studies. We describe methods that should allow researchers to evaluate and in many instances overcome many of these problems. These methods rely on the use of multiple genetic markers and can be used to investigate and control for the following problems: 1.  genetic stratification; 2.  allelic and locus heterogeneity; 3.  indirect association and linkage disequilibrium; 4.  sample heterogeneity; 5.  the assessment of statistical significance; 6.  the evaluation of the power and likely yield of a case/control study; and 7.  The assessment and use of admixture. We showcase these methods with actual data and argue that because of its simplicity, the case/control design may become a design of choice rather than a design by default for future genetic epidemiology studies.