Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditioning on the IBD sharing value at the estimated trait locus of the reference region. Since markers considered are typically non-fully informative, the IBD sharing at each marker needs to be estimated (or imputed). In this report, we propose an alternative approach to deal with the IBD sharing in the reference region. This new approach makes full use of the observed data without having to categorize the imputed IBD sharing as needed in Liang et al. ([2001b] Genet. Epidemiol. 21:105-122). We compare these two approaches by simulating data from a variety of two-locus models including heterogeneity, additive and multiplicative with either fully informative markers or non-fully informative markers. The performance of both approaches is quite comparable showing consistent estimates of the trait locus and key genetic parameters.