OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common developmental disorder. Although a few confirmed associations have emerged from candidate gene studies, these have shown the same limitations that have become evident in the study of other complex diseases, often with inconsistent and nonreplicated results across different studies. METHODS: In this report, 27 ADHD candidate genes were explored in greater depth using high-density tag single nucleotide polymorphism (SNP) genotyping. Association with 557 SNPs was tested using the transmission disequilibrium test in 270 nuclear pedigrees selected from an ongoing ADHD genetic study that includes all disease subtypes. RESULTS: SNPs in seven genes including SLC1A3, SLC6A3, HTR4, ADRA1A, HTR2A, SNAP25, and COMT showed a nominal level of association with ADHD (P values <0.05), but none remained significant after a stringent correction for the total number of tests performed. CONCLUSION: The strongest signal emerged from SNPs in the promoter region (rs3808585) and in an intron (rs17426222, rs4732682, rs573514) of ADRA1A, all located within the same haplotype block. Some of the SNPs in HTR2A and COMT have already been reported by others, whereas other SNPs will need confirmation in independent samples.
OBJECTIVES:Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common developmental disorder. Although a few confirmed associations have emerged from candidate gene studies, these have shown the same limitations that have become evident in the study of other complex diseases, often with inconsistent and nonreplicated results across different studies. METHODS: In this report, 27 ADHD candidate genes were explored in greater depth using high-density tag single nucleotide polymorphism (SNP) genotyping. Association with 557 SNPs was tested using the transmission disequilibrium test in 270 nuclear pedigrees selected from an ongoing ADHD genetic study that includes all disease subtypes. RESULTS: SNPs in seven genes including SLC1A3, SLC6A3, HTR4, ADRA1A, HTR2A, SNAP25, and COMT showed a nominal level of association with ADHD (P values <0.05), but none remained significant after a stringent correction for the total number of tests performed. CONCLUSION: The strongest signal emerged from SNPs in the promoter region (rs3808585) and in an intron (rs17426222, rs4732682, rs573514) of ADRA1A, all located within the same haplotype block. Some of the SNPs in HTR2A and COMT have already been reported by others, whereas other SNPs will need confirmation in independent samples.
Authors: Josephine Elia; Joseph T Glessner; Kai Wang; Nagahide Takahashi; Corina J Shtir; Dexter Hadley; Patrick M A Sleiman; Haitao Zhang; Cecilia E Kim; Reid Robison; Gholson J Lyon; James H Flory; Jonathan P Bradfield; Marcin Imielinski; Cuiping Hou; Edward C Frackelton; Rosetta M Chiavacci; Takeshi Sakurai; Cara Rabin; Frank A Middleton; Kelly A Thomas; Maria Garris; Frank Mentch; Christine M Freitag; Hans-Christoph Steinhausen; Alexandre A Todorov; Andreas Reif; Aribert Rothenberger; Barbara Franke; Eric O Mick; Herbert Roeyers; Jan Buitelaar; Klaus-Peter Lesch; Tobias Banaschewski; Richard P Ebstein; Fernando Mulas; Robert D Oades; Joseph Sergeant; Edmund Sonuga-Barke; Tobias J Renner; Marcel Romanos; Jasmin Romanos; Andreas Warnke; Susanne Walitza; Jobst Meyer; Haukur Pálmason; Christiane Seitz; Sandra K Loo; Susan L Smalley; Joseph Biederman; Lindsey Kent; Philip Asherson; Richard J L Anney; J William Gaynor; Philip Shaw; Marcella Devoto; Peter S White; Struan F A Grant; Joseph D Buxbaum; Judith L Rapoport; Nigel M Williams; Stanley F Nelson; Stephen V Faraone; Hakon Hakonarson Journal: Nat Genet Date: 2011-12-04 Impact factor: 38.330
Authors: Jennifer A Accardo; Carole L Marcus; Mary B Leonard; Justine Shults; Lisa J Meltzer; Josephine Elia Journal: J Dev Behav Pediatr Date: 2012-02 Impact factor: 2.225
Authors: Li Yang; Qiujin Qian; Lu Liu; Haimei Li; Stephen V Faraone; Yufeng Wang Journal: J Neural Transm (Vienna) Date: 2012-12-25 Impact factor: 3.575
Authors: Ziarih Hawi; Natasha Matthews; Joseph Wagner; Robyn H Wallace; Tim J Butler; Alasdair Vance; Lindsey Kent; Michael Gill; Mark A Bellgrove Journal: PLoS One Date: 2013-04-12 Impact factor: 3.240