Genotypic relative risks under ordered restriction

Genet Epidemiol. 1998;15(2):135-46. doi: 10.1002/(SICI)1098-2272(1998)15:2<135::AID-GEPI3>3.0.CO;2-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Case-Control Studies
  • Computer Simulation
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Likelihood Functions
  • Models, Genetic*
  • Risk Assessment
  • Statistics as Topic / methods*