Asthma Clinical Trial
Official title:
Case-Control Association Studies and Genetic Confounding
The purpose of this study is to examine the effectiveness of approaches to correct for the effects of population stratification on case-control genetic association studies.
BACKGROUND:
In racially admixed populations, genetic associations may be confounded by population
stratification. To control for population stratification, statistical methods that use
marker genotype data to infer population structure have been proposed as an alternative to
family-based tests of association. However, there are limited empirical data on how these
methods perform in real populations. This study will use well characterized populations of
Mexican and Puerto Rican asthmatics, their parents, and control subjects recruited from the
same sites to examine the effectiveness of approaches to correct for the effects of
population stratification on case-control genetic association studies.
DESIGN NARRATIVE:
This study has three specific aims: 1) To test and compare methods of detecting and
correcting for population stratification, the study will genotype a total of 100 ancestral
informative markers (AIMs) for 400 asthma cases and an equal number of control subjects.
These AIMs will then be used with three statistical methods developed to detect and correct
for population stratification. The number and characteristics of markers required to correct
false positive associations between AIMs, asthma, and asthma quantitative traits will be
evaluated and compared; 2) To compare the power of genomically adjusted case-control studies
to the Transmission Disequilibrium Test (TDT). An allele from each of the 100 AIMs will be
considered as a risk factor for a simulated "phenotype." The association between phenotypes
and each AIM will be tested with the TDT and with a case-control analysis after adjustment
for stratification to compare the false negative rates for these study designs. 3) To use
the results from aim 1 and 2 to define an optimal approach for analysis and interpretation
of case-control association studies in these populations and apply this approach to analyze
the association between asthma and a series of candidate genes. The results of these studies
should provide important insights into optimal methods to control for population
stratification in case-control association studies, thereby facilitating the inclusion of
admixed populations in future genetic studies of complex diseases such as asthma.
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Observational Model: Family-Based, Time Perspective: Retrospective
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