Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK

We describe a family-based sample of individuals with reading disability co llected as part of a quantitative trait loci (QTL) mapping study. Eighty-ni ne nuclear families (135 independent sib-pairs) were identified through a s ingle proband using a traditional discrepancy score of predicted/actual rea ding ability and a known family history. Eight correlated psychometric meas ures were administered to each sibling, including single word reading, spel ling, similarities, matrices, spoonerisms, nonword and irregular word readi ng, and a pseudohomophone test. Summary statistics for each measure showed a reduced mean for the probands compared to the co-sibs, which in turn was lower than that of the population. This partial co-sib regression back to t he mean indicates that the measures are influenced by familial factors and therefore, may be suitable for a mapping study. The variance of each of the measures remained largely unaffected, which is reassuring for the applicat ion of a QTL approach. Multivariate genetic analysis carried out to explore the relationship between the measures identified a common factor between t he reading measures that accounted for 54% of the variance. Finally the fam iliality estimates (range 0.32-0.73) obtained for the reading measures incl uding the common factor (0.68) supported their heritability. These findings demonstrate the viability of this sample for QTL mapping, and will assist in the interpretation of any subsequent linkage findings in an ongoing geno me scan.