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Power comparison between population-based case-control studies and family-based transmission-disequilibrium tests: An empirical study
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Power comparison between population-based case-control studies and family-based transmission-disequilibrium tests: An empirical study
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Journal Article
Power comparison between population-based case-control studies and family-based transmission-disequilibrium tests: An empirical study
2012
Overview
Background: There are two major classes of genetic association
analyses: population based and family based. Population-based
case-control studies have been the method of choice due to the ease of
data collection. However, population stratification is one of the major
limitations of case-control studies, while family-based studies are
protected against stratification. In this study, we carry out extensive
simulations under different disease models (both Mendelian as well as
complex) to evaluate the relative powers of the two approaches in
detecting association. Materials and Methods: The power comparisons
are based on a case-control design comprising 200 cases and 200
controls versus a Transmission Disequilibrium Test (TDT) or Pedigree
Disequilibrium Test (PDT) design with 200 informative trios. We perform
the allele-level test for case-control studies, which is based on the
difference of allele frequencies at a single nucleotide polymorphism
(SNP) between unrelated cases and controls. The TDT and the PDT are
based on preferential allelic transmissions at a SNP from heterozygous
parents to the affected offspring. We considered five disease modes of
inheritance: (i) recessive with complete penetrance (ii) dominant with
complete penetrance and (iii), (iv) and (v) complex diseases with
varying levels of penetrances and phenocopies. Results: We find that
while the TDT/PDT design with 200 informative trios is in general more
powerful than a case-control design with 200 cases and 200 controls
(except when the heterozygosity at the marker locus is high), it may be
necessary to sample a very large number of trios to obtain the
requisite number of informative families. Conclusion: The current study
provides insights into power comparisons between population-based and
family-based association studies.
Publisher
Medknow Publications on behalf of Indian Society of Human Genetics
