title: Association of ADHD and the Protogenin gene in the chromosome 15q21.3 reading disabilities linkage region.
abstract: Twin studies indicate genetic overlap between symptoms of attention deficit hyperactivity disorder (ADHD) and reading disabilities (RD), and linkage studies identify several chromosomal regions possibly containing common susceptibility genes, including the 15q region. Based on a translocation finding and association to two specific alleles, the candidate gene, DYX1C1, has been proposed as the susceptibility gene for RD in 15q. Previously, we tested markers in DYX1C1 for association with ADHD. Although we identified association for haplotypes across the gene, we were unable to replicate the association to the specific alleles reported. Thus, the risk alleles for ADHD are yet to be identified. The susceptibility alleles may be in a remote regulatory element, or DYX1C1 may not be the risk gene. To continue study of 15q, we tested a coding region change in DYX1C1, followed by markers across the gene Protogenin (PRTG) in 253 ADHD nuclear families. PRTG was chosen based on its location and because it is closely related to DCC and Neogenin, two genes known to guide migratory cells and axons during development. The markers in DYX1C1 were not associated to ADHD when analyzed individually; however, six markers in PRTG showed significant association with ADHD as a categorical trait (P = 0.025-0.005). Haplotypes in both genes showed evidence for association. We identified association with ADHD symptoms measured as quantitative traits in PRTG, but no evidence for association with two key components of reading, word identification and decoding was observed. These findings, while preliminary, identify association of ADHD to a gene that potentially plays a role in cell migration and axon growth.
authors.affiliation: Genetics and Development Division, The Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: K G
authors.initials: KG
authors.lastname: Wigg
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: J
authors.initials: J
authors.lastname: Crosbie
authors.forename: R
authors.initials: R
authors.lastname: Tannock
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: A
authors.initials: A
authors.lastname: Ickowicz
authors.forename: M
authors.initials: M
authors.lastname: Malone
authors.forename: R
authors.initials: R
authors.lastname: Schachar
authors.forename: C L
authors.initials: CL
authors.lastname: Barr
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004410:Dyslexia / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; C478878:DNAAF4 protein, human; D005819:Genetic Markers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins