Pedigree of the kindred. The symbol on top represents the common ancestor. Filled symbols indicate individuals affected with ADHD. The double line denotes a mar- riage between parents with a shared ancestor. A diamond symbol has been used to mask the sex of the patients, in order to protect patient confidentiality. sis of ADHD, confirmed by a second informant, is more suitable for future gene-finding studies. Second, we showed that children with the inattentive subtype of ADHD are in our population genetically more cluster related than those with the combined type. We confirmed previous studies which found that ADHD clusters in families (Xxxxxxx et al., 2001). We found, however, that patients with the inattentive phenotype were more closely related. Us- ing extensive data-based genealogical information of the patients included in this study, we also found evidence of inbreeding. The presence of inbreed- ing strongly suggests that recessive genes are involved. In those which the diagnosis was confirmed by two informants as well as those with the com- bined phenotype, inbreeding was significantly increased in comparison to the control group. The chances that two similar recessive mutations are transmit- ted to a child are therefore much more likely when they come from the same ancestor in a pedigree with so-called ”loops”, than in an out-bred pedigree with non-related parents. So far, only genes with a dominant effect have been considered in the aetiology of ADHD. A major limitation of our study is the small sample. In order to use in- formation on genealogy we had to restrict our study to an isolated population for which we have genealogical data available. This has limited the number of patients eligible for the study. Nevertheless, the relation between the number of informants and the distance of relationship between patients was found to be statistically significant, even with this small sample size. The advantage of working with an isolated community is that we have detailed information on genealogy, which is not available in the general population. The loops identi- fied in seven of fifteen patients who were linked to a common ancestor further suggest the involvement of a gene with a recessive effect. We have previously shown that, in this population with inbreeding, homozygosity mapping is a powerful approach in detecting genes with recessive effects (Xxxxxxxx et al., 2003). Of note is the fact that in our study the mean kinship coefficients for ADHD are relatively high. In t...
