Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder

• Published in: American journal of medical genetics 2000-06, Vol.96 (3), p.262-267
• Main Authors: Barr, Cathy L., Wigg, Karen G., Bloom, Stacey, Schachar, Russell, Tannock, Rosemary, Roberts, Wendy, Malone, Molly, Kennedy, James L.
• Format: Article
• Language: English
• Subjects: Adolescent; Alleles; Attention Deficit Disorder with Hyperactivity - genetics; attention-deficit hyperactivity disorder; Chi-Square Distribution; Child; dopamine receptor D4; Family Health; genetics; Haplotypes; Humans; Linkage Disequilibrium; Polymorphism, Restriction Fragment Length; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D4; Statistics as Topic; Transmission Disequilibrium Test; Tyrosine 3-Monooxygenase - genetics; tyrosine hydroxylase
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/1096-8628(20000612)96:3<262::AID-AJMG5>3.0.CO;2-8

Several studies have suggested a possible association of a polymorphism at the dopamine D4 receptor gene and attention‐deficit hyperactivity disorder [LaHoste et al., 1996; Rowe et al., 1998; Smalley et al., 1998; Sunohara et al., submitted; Swanson et al., 1998]. The allele reported to be associated with attention‐deficit hyperactivity disorder (ADHD) is the allele with seven copies of the 48 bp repeat in the third exon. We extend our study of the dopamine D4 gene and ADHD by testing for linkage using two additional polymorphisms in the dopamine D4 receptor gene and a polymorphism in the closely linked gene, tyrosine hydroxylase. We also searched for two previously reported deletions, a 13 bp and a 21 bp deletion in the first exon. We examined the haplotypes of three polymorphisms of the D4 receptor gene and observed biased transmission of two of these haplotypes. Our findings further support the role of the dopamine D4 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:262–267, 2000. © 2000 Wiley‐Liss, Inc.