TY - JOUR
T1 - Transmission disequilibrium test with discordant sib pairs when parents ae available
AU - Deng, Hong Wen
AU - Chen, Wei Min
AU - Recker, Robert R.
N1 - Funding Information:
Acknowledgements The investigators of this study were partially supported by grants from Health Future Foundation, NIH K01 grant AR02170–01, NIH R01 grants AR45349-01 and GM60402–01A1, NIH grant P01 DC01813–07, grants from State of Nebraska Cancer and Smoking Related Disease Program (LB598) and Nebraska Tobacco Settlement Fund (LB692), US Department of Energy grant DE-FG03–00ER63000/A00, grants (30025025 and 30170504) from National Science Foundation of China, and grants from the HuNan Normal University and the Ministry of Education of China. W.-M. Chen received a tuition waiver from the Graduate School of Creighton University when conducting the research for this project. We are grateful to the two anonymous reviewers for their generous help and careful comments that improved our manuscript.
PY - 2002/5
Y1 - 2002/5
N2 - The transmission disequilibrium test (TDT) has been employed to map disease susceptibility loci (DSL), while being immune to the problem of population admixture. The customary TDT test (TDTD) was developed for affected child(ren) and their parents and was most often applied to case-parent trios. Recently, the TDT has been extended to the situations when (1) parents are not available but affected and nonaffected sibs from each family are available, (2) unrelated control-parent trios are available for combined analyses with case-parent trios (TDTDC), and (3) large pedigrees. For many diseases, affected children in the case-parent trios enlisted into the TDTD have unaffected sibs who can be recruited. We present an extension of the TDT by effectively incorporating one unaffected sib of each of the affected children in the case-parent trios into a single analysis (TDTDS, where DS denotes discordant sib pairs). We have developed a general analytical method for computing the statistical power of the TDTDS under any genetic model, the accuracy of which is validated by computer simulations. We compare the power of the TDTD, TDTDS under a range of parameter space and genetic models. We find that the TDTDS is generally more powerful than the TDTDC and TDTD, particularly when the disease is prevalent (>30%) in the population. The relative power of the TDTD and the TDTDS largely depends upon the allele frequencies and genetic effects at the DSL, whereas the recombination rate, the degree of linkage disequilibrium, and the marker allele frequencies have little effect. Importantly, the TDTDS not only may be more powerful, it also has the advantage of being able to test for segregation distortion that may yield false linkage/association in the TDTD.
AB - The transmission disequilibrium test (TDT) has been employed to map disease susceptibility loci (DSL), while being immune to the problem of population admixture. The customary TDT test (TDTD) was developed for affected child(ren) and their parents and was most often applied to case-parent trios. Recently, the TDT has been extended to the situations when (1) parents are not available but affected and nonaffected sibs from each family are available, (2) unrelated control-parent trios are available for combined analyses with case-parent trios (TDTDC), and (3) large pedigrees. For many diseases, affected children in the case-parent trios enlisted into the TDTD have unaffected sibs who can be recruited. We present an extension of the TDT by effectively incorporating one unaffected sib of each of the affected children in the case-parent trios into a single analysis (TDTDS, where DS denotes discordant sib pairs). We have developed a general analytical method for computing the statistical power of the TDTDS under any genetic model, the accuracy of which is validated by computer simulations. We compare the power of the TDTD, TDTDS under a range of parameter space and genetic models. We find that the TDTDS is generally more powerful than the TDTDC and TDTD, particularly when the disease is prevalent (>30%) in the population. The relative power of the TDTD and the TDTDS largely depends upon the allele frequencies and genetic effects at the DSL, whereas the recombination rate, the degree of linkage disequilibrium, and the marker allele frequencies have little effect. Importantly, the TDTDS not only may be more powerful, it also has the advantage of being able to test for segregation distortion that may yield false linkage/association in the TDTD.
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U2 - 10.1007/s00439-002-0675-9
DO - 10.1007/s00439-002-0675-9
M3 - Article
C2 - 12073016
AN - SCOPUS:0036590027
VL - 110
SP - 451
EP - 461
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 5
ER -