The analysis of case-control data to detect candidate genes

Case-control data have historically been used to detect environmental effects causing disease, but are now being used to detect genetic effects as well, typing the cases and controls for candidate gene loci. For each candidate gene the resulting measure on each subject is a genotype, comprising two alleles. Because the alleles within a person are typically not independent, the analysis poses both difficulties and opportunities. Armitage's trend test can be used to determine if a particular allele is more frequent among cases than controls, and a test for departure from Hardy-Weinberg equilibrium proportions can be used to provide a further indication that the typed locus marks a genomic region where a disease susceptibility gene lies. These two pieces of information are pooled to obtain a test that better maintains validity in the presence of population structure/heterogeneity and is more powerful than either individual test.