A normalized identity-by-state statistic for linkage analysis of sib pairs

A sib-pair analysis was performed on a simulated data set for a fictitious disease, with a prevalence of approximately 3% to 6%. The disease could manifest itself in a severe or mild form and the analyses focused primarily on families with the mild form, barring any misdiagnoses. The numbers of shared genes identical by descent (IBD) and identical by state (IBS) were used to detect linkage between the marker loci and the disease. The results of the two methods were compared. We considered the distribution of the number of shared alleles IBS (for different parental allele combinations) and suggest a normalized IBS method. A large proportion of pedigrees in this data set had at least one homozygous parent or both parents sharing a common gene, thus generating the need for an adjustment of the IBS method. Our results indicate that the normalized IBS method gives results similar to those obtained by the traditional IBD approach. The adjusted score requires no assumptions be made with regard to the allele frequencies.