title: Genotypic relative risks under ordered restriction.
abstract: In mapping diseases of complex aetiology, conventional linkage approaches narrow the location of the disease susceptibility locus to quite a large region so that candidate gene association studies are then necessary to further isolate these genes. However, even in the simplest scenario where the candidate locus is bi-allelic, two statistical tests with various correcting factors have been proposed: a chi-square 1 df test (counting chromosomes) which may be slightly conservative and a 2 df chi-square test (counting genotypes) which may lack power because of the extra degree of freedom. This paper introduces a better and more powerful alternative which turns out to be a compromise between the two existing statistical tests. The asymptotic distribution of this test statistic is determined and the efficacy of the 3 tests are compared under different genetic models by simulation.
authors.affiliation: MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, United Kingdom. m.chiano@umds.ac.uk
authors.forename: M N
authors.initials: MN
authors.lastname: Chiano
authors.forename: D G
authors.initials: DG
authors.lastname: Clayton
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics; D016022:Case-Control Studies; D003198:Computer Simulation; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D018570:Risk Assessment; D013223:Statistics as Topic / Q000379:methods*