title: LOD score exclusion analyses for candidate QTLs using random population samples.
abstract: While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes as putative QTLs using random population samples. Previously, we developed an LOD score exclusion mapping approach for candidate genes for complex diseases. Here, we extend this LOD score approach for exclusion analyses of candidate genes for quantitative traits. Under this approach, specific genetic effects (as reflected by heritability) and inheritance models at candidate QTLs can be analyzed and if an LOD score is < or = -2.0, the locus can be excluded from having a heritability larger than that specified. Simulations show that this approach has high power to exclude a candidate gene from having moderate genetic effects if it is not a QTL and is robust to population admixture. Our exclusion analysis complements association analysis for candidate genes as putative QTLs in random population samples. The approach is applied to test the importance of Vitamin D receptor (VDR) gene as a potential QTL underlying the variation of bone mass, an important determinant of osteoporosis.
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, ChangSha, Hunan 410081, PR China. deng@creighton.edu
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D015519:Bone Density / Q000235:genetics; D003198:Computer Simulation; D005260:Female; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D018167:Receptors, Calcitriol / Q000235:genetics; D018401:Sample Size; D013131:Spine / Q000737:chemistry
chemical_list: D018167:Receptors, Calcitriol