Rapid development in biotechnology has enhanced the opportunity to deal with multipoint gene mapping for complex diseases, and association studies using case-parent trio design have generated much attention recently. We first propose a m ultipoint linkage disequilibrium (LD) mapping approach using the case-parent trio design for qualitative traits. The prim ary statistic is the preferential allele transmission statistic from either parent to an affected child at an arbitrary location within a chromosomal region framed by several genetic markers. The generalized estimating equation method is adopted, built on a model for the expected preferential transmission statistic. This approach is valid regardless of the underlying genetic model. The major assum ption is that there is no more than one trait locus in the study region. The location of the trait locus and its confidence interval can be estimated. Data from a family study of asthma conducted in Barbados is used as an illustration.

This approach is extended for quantitative traits. Sample size calculations show that sampling trios of offspring and their parents from either extremely low or extremely high probands provides greater statistical power than sam pling in the interm ediate range. A unified approach utilizing sampling through extreme values of the quantitative trait in offspring is used to estimate the map position of a quantitative trait locus and its confidence interval. The proposed method is illustrated using data on total serum IgE levels conducted in Barbados.

For family-based studies, the method for detecting linkage and LD with one locus at a time may not capture the assumed interaction between trait loci efficiently. For qualitative traits, we also extend this approach for assessing evidence of linkage and LD in a targeted region by incorporating evidence from the unlinked region using the case-parent trio design. Our goal is to estimate the map position of a trait locus and to calculate its confidence interval in th e targeted region by incorporating evidence of linkage and LD from the unlinked region. Finally, we apply this approach to the chromosomes 8 and 11 data in the African American subset of the collaborative study on the genetics of asthma.