The use of random controls in genetic association studies.
BACKGROUND
The optimal control sample would be ethnically-matched and at minimal risk of developing the disease. Alternatively, one could collect random individuals from the population or select individuals to reduce the number of at-risk individuals in the sample. The effect of randomly selected individuals in a control sample on the statistical power and the odds ratio estimate was investigated.


METHODS
Case and control genotype distributions were simulated using standard genetic models with an additional term representing the proportion of unidentified cases in the control sample. Power and odds ratio were calculated from the genotype distributions generated under different sampling scenarios using established methods.


RESULTS
Random sampling of controls resulted in a loss in power and a reduction in the odds ratio estimate to a degree that is determined by the proportion of random sampling and the prevalence of the disease. Random sampling resulted in a 19% loss in power for a disease having prevalence of 0.20, compared to a control sample that contained no at-risk individuals. Having random controls results in a decrease in the odds ratio estimate.


CONCLUSIONS
Investigators planning case-control genetic association studies should be aware of the statistical costs of different ascertainment approaches.
Epidemiology Division, Department of Medicine, University of California, Irvine, 92697-7550, USA. cgarner@uci.edu
Chad
C
Garner
D000483:Alleles; D016022:Case-Control Studies; D005787:Gene Frequency; D005819:Genetic Markers; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D015233:Models, Statistical; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D012306:Risk
D005819:Genetic Markers