A Twin Study of the Etiology of Comorbidity: Attention-deficit Hyperactivity Disorder and Dyslexia JEFFREY W. GILGER, PH.D., BRUCE F. PENNINGTON, PH.D., AND JOHN C. DEFRIES, PH.D. Abstract. Monozygotic and dizygotic twin pairs, in which at least one member of each pair is reading disabled (RD), were assessed for attention-deficit hyperactivity disorder (ADHD). Within pair cross-concordances of the RD and ADHD qualitative diagnoses for monozygotic twins were larger than for dizygotic twins, although not significantly so (p < 0.10). Thus, the data suggest that RD and ADHD may be primarily genetically independent. However, trends in the data and subtype analyses suggest that in some cases RD and ADHD may occur together because of a shared genetic etiology and that a genetically mediated comorbid subtype may exist. J. Am. Acad. Child Adolesc. Psychiatry, 1992, 31, 2:343-348. Key Words: comorbidity, dyslexia, attention-deficit hyperactivity disorder, genetics, twins. Comorbidity or the association of two disease states in an individual frequently occurs for psychiatric disorders. Familiar examples include the association between attention deficit hyperactivity disorder (ADHD) and learning disabili- ties, and depression with other psychiatric disturbances such as alcoholism (American Psychiatric Association, 1987). In addition to causing problems for diagnosis and treatment, comorbidity raises interesting questions pertaining to the etiology and mutual interdependence of the comorbid disor- ders. The comorbidity of ADHD and reading disabilities (RD) has been well documented (Cantwell and Baker, 1991; Cant- well and Satterfield, 1978; Holobrow and Berry, 1986; McGee et aI., 1987; Shaywitz and Shaywitz, 1988). It is possible that in some cases RD and ADHD may cooccur because of a common etiology, either genetic or environ- mental. A genetic contribution to both RD and ADHD, each as separate disorders, has in fact been demonstrated (Rutter et aI., 1990), but, at this time, no genetic analyses have been reported that examine the etiology of RD-ADHD comorbid- ity. One method to assess the genetic contribution to the co- morbidity observed for any two qualitative characters is to examine the pattern of cosegregation of the two disorders in families (e.g., Pauls et aI., 1986). Basically, relatives of probands can be examined for evidence that the two diseases occur together more frequently than is expected by chance. Should the cosegregation rates differ significantly from ex- Accepted July 17, 1991. Drs. Gilger and Pennington are from the University of Denver. Dr. DeFries is from the University of Colorado. During preparation of this article, Dr. Gilger was supported in part by grant MH15442 through the University of Colorado. Dr. Pennington was supported by a NIMH RSDA (MH00419), project grant (MH38820), and grants from the March of Dimes (12-135) and the Orton Dyslexia Society. The twin research reported in this paper was supported in part by NICHD Grants HD 11681 and HD 27802. We thank the staffandfamilies of the Colorado school districts that participated in the twin study. Reprint requests to Dr. Gilger, University of Denver, Department of Psychology, 2155 S. Race Street, Denver, CO, 80208. 0890-8567/92/3102-Q343$03.00/O©1992 by the American Acad- emy of Child and Adolescent Psychiatry. J. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992 pectation, it is concluded that their association is due to the effects of some common etiological mechanism. Pauls and colleagues (1986) used this method to rule out a genetic basis to the comorbidity found for ADHD and Gilles de la Tourette's syndrome. The purpose of this paper is to provide the first genetic cosegregation analysis of ADHD-RD comorbidity. Al- though cosegregation analysis of family data is a useful technique that is currently being applied to psychiatric disor- ders, an underutilized and potentially more powerful method to identify the genetic and environmental components of comorbidity is the study of twins (Gilger, in press). Unlike family studies, which confound genetic and environmental influences, twin data facilitate a separate analysis of genetic and environmental effects. Therefore, in this paper monozy- gotic (MZ) and dizygotic (DZ) twin cross-concordances for RD and ADHD were compared. Because MZs are geneti- cally identical, whereas DZs share only half of their segre- gating genes on average, a significantly larger MZ than DZ cross-concordance would provide evidence for a common genetic etiology for the observed comorbidity. Method Subjects Subjects in the present study are the subset of twin pairs participating in the ongoing Colorado Reading Project (CRP) (DeFries, 1985) for which complete behavioral infor- mation was available. Twin pairs in the CRP were identified from 27 cooperating school districts within a 150 mile radius of Denver, Colorado. After a pair was identified, parental permission was sought to examine the twins' school records for evidence of reading problems (e.g., low standardized test scores, referral to a reading therapist, or referrals from classroom teachers or school psychologists). For the reading disabled group, twin pairs in which at least one member of the pair had a positive school history of reading problems was identified. A sample of matched control twin pairs, where neither member of the pair had a history of reading problems, was also ascertained. All subjects received an extensive battery of psychometric tests, including subtests from the Peabody Individual Achievement Test (Dunn and Markwardt, 1970) and the Wechsler Intelligence Scales for 343