Analysis of case-parental control studies: method for the study of associations between disease and genetic markers

Case-control studies using parents of case subjects as the control subjects provide an innovative way to study associations of genetic markers with disease risk. This approach, sometimes called the haplotype-relative risk method, has received recent attention because the use of parents as control subjects may reduce or eliminate the confounding associated with differences in race, ethnicity, or genetic background. We provide a new method for analysis of such case-parental control studies. The method of analysis is noniterative and yields simple estimates of risk ratios associated with genetic markers. It easily accommodates the situation in which data are available from only one parent. Although we illustrate the approach for a locus with two alleles, the analyses extend immediately to loci with multiple alleles.