Multipoint analysis using affected sib pairs: Incorporating linkage evidence from unlinked regions

In this paper, we proposed a multipoint method to assess evidence of linkag e to one region by incorporating linkage evidence from another region. This approach uses affected sib pairs in which the number of alleles shared ide ntical by descent (IBD) is the primary statistic. This generalized estimati ng equation (GEE) approach is robust in that no assumption about the mode o f inheritance is required, other than assuming the two regions being consid ered are unlinked and that there is no more than one susceptibility gene in each region. The method proposed here uses data from all available familie s to simultaneously test the hypothesis of statistical interaction between regions and to estimate the location of the susceptibility gene in the targ et region. As an illustration, we have applied this GEE method to an asthma sib pair study (Wjst et al. [1999] Genomics 58:1-8), which earlier reporte d evidence of linkage to chromosome 6 but showed no evidence for chromosome 20. Our results yield strong evidence to chromosome 20 (P value = 0.0001) after incorporating linkage information from chromosome 6. Furthermore, it estimates with 95% certainty that the map location of the susceptibility ge ne is flanked by markers D20S186 and D20S101, which are approximately 16.3 cM apart. (C) 2001 Wiley-Liss, Inc.