Using both cases and controls for testing hardy-weinberg proportions in a genetic association study.
OBJECTIVE
Assessment of the Hardy-Weinberg proportion (HWP) in controls has been widely used as a quality control measure in case-control association studies. However, when the disease being studied is common, controls might not represent the general population, which could result in inaccurate HWP test results. Such results could lead investigators to discard important single-nucleotide polymorphisms (SNPs) that could potentially be causal. In this paper, we showed the inappropriateness of the HWP test in controls and proposed a mixture HWP (mHWP) exact test using a mixture sample that mimics the general population.


METHODS
The mHWP exact test estimates HWP in a mixture sample that is a combination of both cases and controls proportional to the prevalence of disease. We implemented a re-sampling procedure to construct mixture samples and then obtained the empirical p value of HWP in the general population. Simulation studies were performed to investigate the performance of the proposed mHWP exact test. The method was also applied to a genetic association study of obesity.


RESULTS
The results showed that the mHWP exact test is more likely than either the traditional HWP method in controls or the likelihood-based approach to keep causal SNPs for further analysis when the disease is more common.


CONCLUSIONS
The mHWP exact test using a mixture sample is a better HWP test for case-control genetic association studies than the traditional HWP in controls or the likelihood-based approach, and it will improve our ability to keep causal SNPs in the case-control genetic association studies.
Wang
Jian
J
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Shete
Sanjay
S
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods / Q000706:statistics & numerical data; D055106:Genome-Wide Association Study / Q000379:methods* / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D015233:Models, Statistical; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult