Colorado Twin Study and Reading Disability

Since 1982, IBG faculty, staff, and students have been collecting and analyzing data from identical and fraternal twin pairs in which at least one member of each pair had a reading difficulty. Twin pairs with a school history of reading problems, and a comparison sample with no reading difficulties, are being systematically ascertained through 27 cooperating school districts in Colorado. These children are administered an extensive batery of tests at IBG, and in the laboratories of Professor Richard K. Olson and Bruce F. Pennington. To date, we have tested over 200 pairs of identical twins and over 150 pairs of same-sex fraternal twins in which at least one twin meets our criteria for reading disability (school history of reading problems, low test scores on reading performance, a Verbal or Performance IQ score of at least 90, no serious neurological, emotional or behavioral problems, and no uncorrected visual or auditory acuity deficits).

In approximately two-thirds of the pairs of identical twins, both memebers of the pair are affected, whereas the corresponding concordance rate for reading disability in the same-sex fraternal twins is only about a third, a highly significant difference. Although this compairison of concordance rates in identical and fraternal twin pairs clearly indicates that reading disability is due in part to genetic influences, multiple regression analyses of reading performance data provide a statistically more powerful and versatile test (DeFries, J.C., & Fulker, D.W., 1985, Behavioral Genetics, 15, 467-473). When reading performance data were recently subjected to multiple regression analysis (sometimes referred to as "DF analysis"), we found that over half (0.56) of the reading deficit of the affected members of these twin pairs was due to genetic influences, a very highly significant result.

In addition to obtaining compelling evidence for the heritable nature of reading disability, we have also recenty found that the etiology of reading disability differs as a function of IQ and age. Results obtained from DF analyses indicate that heritable influences are substantially more important for twin pairs with an average IQ over 100 than for those with a lower IQ (0.75 versus 0.43, respecively). Also, we have obtained some evidence that the causes of reading and spelling deficits may change differentially as a function of age. Whereas deficits in reading performance are somewhat more heritable in younger children than in older children (0.64 vs. 0.47), the converse pattern occurred for spelling difficulties (0.52 vs. 0.68).

Finally, the multiple regression analysis of twin data has also been adapted to find the chromosomal location of a gene or quantitative trait locus (QTL) for susceptibility to reading-related difficulties. Using methods developed by Professor David W. Fulker and his former graduate student, Dr. Lon R. Cardon (University of Oxford, U.K.), we analyzed reading performance data from fraternal twin pairs and siblings of twins who had been genotyped for DNA markers by Professor Shelley D. Smith, Boys Town National Research Hospital, Omaha, NE. Results of this analysis provided evidence for a possible QTL for reading disability in a small region of chromosome 6 (Cardon, L.R., et al., 1994, Science, 266, 276-279). This evidence for linkage has subsequently been confirmed by three independent groups of investigators (one at Yale University and two in England), as well as by our own group when a completely independent sample of data from fraternal twin pairs and siblings was analyzed (Gayan, J., et al., in press, American Journal of Human Genetics).

With funding from the National Institute of Child Health and Human Development, we are continuing to obtain data from additional fraternal twin and sibling pairs, and to test additional genetic markers, in order to determine more precisely the location of the putative QTL for reading disability. Once the QTL is localized to a somewhat smaller region, additional molecular genetic methods will be employed to find the gene. In addition to providing important new information about the disorder's primary cause and neurobiological basis, such findings could be used to identify children who are at risk for reading disability, thereby facilitating preschool intervention in children with affected relatives prior to the manifestation of reading deficits, and could also possibly aid in making diagnoses at later ages.

John C. DeFries, Director, IBG