Linkage study of polymorphisms in the gene for myelin oligodendrocyte glycoprotein located on chromosome 6p and attention deficit hyperactivity disorder.

Family and twin studies have shown that there is a substantial genetic contribution to both reading disabilities (RD) and attention deficit hyperactivity disorder (ADHD), and recent twin studies have suggested that the overlap between these phenotypes is largely due to common genetic influences. Studies using a linkage approach to search for genes for susceptibility to RD and ADHD have identified regions linked to each of these phenotypes separately, with recent studies suggesting that some chromosomal regions may contribute to both. Linkage to the human leukocyte antigen (HLA) region has been targeted in particular for RD and ADHD, as both of these disorders have been suggested to be autoimmune. Linkage to the HLA region of 6p for RD has now been reported by several groups. Alleles at two genes in the HLA (C4B and DRB1) have also been reported to be associated with ADHD, prompting one investigator to suggest a possible connection between the linkage of RD and ADHD to this region. The location of the gene for myelin oligodendrocyte glycoprotein (MOG), in the region of 6p with the strongest evidence for linkage to RD, and its proposed role as a minor component of myelin in the central nervous system suggest that it may be a factor in neuronal functioning and therefore a candidate for RD and ADHD. In this study, we tested the gene for linkage to ADHD by genotyping two polymorphisms in the MOG gene-a dinucleotide repeat located upstream from the MOG transcription start site and a Val145Ile substitution in exon 3-in a sample of 104 nuclear families identified through a proband with ADHD. We examined the transmission of the alleles of the Val145Ile and the dinucleotide repeat polymorphisms using the transmission disequilibrium test. We did not observe biased transmission of the alleles at either polymorphism to ADHD probands or siblings. Our findings using this sample do not support the role of the MOG gene in ADHD. Copyright 2001 Wiley-Liss, Inc.