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LOD score exclusion analyses for candidate disease susceptibility genes using case-parents design

Progress in Natural Science:Materials International 2006年第1期16卷 30-38页

作者： DENG Hongwen1,2,3 and GAO Guimin2,4 (1.Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China 2.Osteoporosis Research Center, Creighton University Medical Center, Omaha NE 68131, USA 3. Department of Biomedical Sciences, Creighton University, Omaha NE 68131, USA 4. Virginia Bioin format ics Institute and Department of Statistics, Virginia Polytechnic Institute and State University, Blacksburg VA 24061-0315, USA) Laboratory of Molecular and Statistical Genetics College of Life Sciences Hunan Normal University Changsha 410081 China Osteoporosis Research Center Creighton University Medical Center Omaha NE 68131 United States Department of Biomedical Sciences Creighton University Omaha NE 68131 United States Virginia Bioinformatics Institute and Department of Statistics Virginia Polytechnic Institute and State University Blacksburg VA 24061-0315 United States

The focus of almost all the association studies of candidate genes is to test for their importance. We recently developed a LOD score approach that can be used to test against the importance of candidate genes for complex diseases and quantitative traits in random samples. As a complementary method to regular association analyses, our LOD score approach is powerful but still affected by the population admixture, though it is more conservative. To control the confounding effect of population heterogeneity, we develop here a LOD score exclusion analysis using case-parents design, the basic design of the transmission disequilibrium test (TDT) approach that is immune to population admixture. In the analysis, specific genetic effects and inheritance models at candidate genes can be analyzed and if a LOD score is ≤ - 2. 0, the locus can be excluded from having an effect larger than that specified. Simulations show that this approach has reasonable power to exclude a candidate gene having small genetic effects if it is not a disease susceptibility locus (DSL) with sample size often employed in TDT studies. Similar to association analyses with the TDT in nuclear families, our exclusion analyses are generally not affected by population admixture. The exclusion analyses may be implemented to rule out candidate genes with no or minor genetic effects as supplemental analyses for the TDT. The utility of the approach is illustrated with an application to test the importance of vitamin D receptor (VDR) gene underlying the differential risk to osteoporosis.

关键词： association studies candidate genes case-parents design disease susceptibility locus exclusion mapping LOD score.

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